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Synthesis of P,N-chelate phosphaalkene–oxazoline ligands and their applications in asymmetric catalysis Dugal-Tessier, Julien 2010

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Synthesis of P,N-Chelate Phosphaalkene–Oxazoline Ligands and Their Applications in Asymmetric Catalysis  by  Julien Dugal-Tessier  B.Sc. (Hons.) University of Ottawa, 2005  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF  DOCTOR OF PHILOSOPHY  in The Faculty of Graduate Studies (Chemistry)  THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver)  February 2011  © Julien Dugal-Tessier, 2010  ii ABSTRACT  This thesis outlines the design, synthesis and utilization of phosphaalkene-based ligands for asymmetric catalysis. Transition metal catalysis studies that utilize achiral phosphaalkene-based ligands are reviewed in Chapter 1. In addition, the synthesis and reactivity of phosphaalkenes are briefly introduced in this chapter.  The reactivity of a palladium(II) phosphaalkene complex [MesP=CPh(2-py)⋅PdCl2] bearing the smaller P-Mes substituent compared to the traditional Mes* is described in Chapter 2. This complex was found to be a competent catalyst for the Overman–Claisen rearrangement with yields ranging from 33% to 91%.  In Chapter 3, a modular route to a set of chiral phosphaalkene–oxazoline [PhAk–Ox, R′P=CR′′(C(i-Pr-Ox)R2)] proligands is described. The synthetic route starts from a chiral pool material (L-valine) and generates the P=C bond by a phospha-Peterson reaction. The electronic and steric properties of the proligands (R′, R′′ and R) were modified using this synthetic route. MesP=CPh(C(i-Pr-Ox)Me2) was thermally polymerized to generate poly(methylenephosphine).  The investigation of the coordination chemistry of PhAk–Ox proligands is described in Chapter 4. Rhodium(I) and iridium(I) PhAk–Ox complexes were characterized by X-ray crystallography and NMR spectroscopy. Rhodium(I) PhAk–Ox complexes were found to be active in the asymmetric allylic alkylation of ethyl (1-phenylallyl) carbonate with dimethyl malonate as a nucleophile. The optimal conditions generated products in 37% yield and 66% ee.  The investigations of PhAk–Ox ligands in palladium(0) catalyzed allylic alkylation of 1,3-diphenylpropenyl acetate using malonate type nucleophiles are reported in Chapter 5. The structural modification of the ligand through the incorporation of a gem-dimethyl group  iii [MesP=CPh(C(4-i-Pr-5-Me2-Ox)Me2)] was needed to optimize yields (73–95%) and enantioselectivities (79–92%). Ring-closing metathesis processes were used to generate enantioenriched carbocycles.  To conclude, the results presented in this dissertation represent the highest reported enantioselectivities for a reaction utilizing a phosphaalkene-based ligand. These results also serve as a proof of concept that phosphaalkene ligands can be used in asymmetric catalysis.  iv PREFACE  Sections of this work have previously been published. The information presented in Chapter 2 has been published in Organometallics, for which I performed all the synthetic work and wrote the manuscript in collaboration with both my supervisors Prof. Gregory R. Dake and Prof. Derek P. Gates. The X-ray data was collected, integrated, refined and solved by Dr. Brian O. Patrick. Julien Dugal-Tessier, Gregory, R. Dake and Derek P. Gates. P,N-Chelate Complexes of Pd(II) and Pt(II) Based on a Phosphaalkene Motif: A Catalyst for the Overman–Claisen Rearrangement. Organometallics, 2007, 26, 6481–6486. The proposed route to phosphaalkenes and the syntheses of compounds 3.9a, 3.9b and 3.23a in Chapter 3, and complex [4.5]OTf in Chapter 4 were published in Angewandte Chemie, International Edition, for which I performed all the presented synthetic work and the manuscript was prepared with both my supervisors Prof. Gregory R. Dake and Prof. Derek P. Gates. The X- ray data was collected and integrated by Joshua I. Bates, and the structures were solved and refined with the help of Joshua I. Bates and Dr. Brian O. Patrick. Julien Dugal-Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. The synthesis of compounds 3.10–3.17 in Chapter 3 was published in Heteroatom Chemistry, for which I performed the synthetic work for compounds 3.10–3.17 and Paul-Steffen Kuhn performed initial synthetic investigation under my direct supervision. The manuscript was prepared with both my supervisors Prof. Gregory R. Dake and Prof. Derek P. Gates. Julien Dugal-Tessier, Paul-Steffen Kuhn, Gregory. R. Dake and Derek P. Gates. Synthesis of Functional Phosphines with Ortho-Substituted Aryl Groups: 2-RC6H4PH2 and 2-RC6H4P(SiMe3)2 (R = i-Pr or t-Bu). Heteroatom Chemistry, 2010, 21, 355-360.  v A full account of the work presented in Chapter 3 will be submitted for publication. The synthetic work presented in Chapter 3 was prepared in collaboration with Emmanuel B. Castillo- Contreras, who synthesized compounds 3.18–3.21, and Dr. Eamonn D. Conrad, who synthesized compound 3.24a and secured more material for compounds 3.22a and 3.9b. The X-ray data was collected and integrated by Joshua I. Bates and the structure solved and refined with the help of Joshua I. Bates and Dr. Brian O. Patrick. Julien Dugal-Tessier, Emmanuel B. Castillo-Contreras, Eamonn D. Conrad, Gregory R. Dake and Derek P. Gates, to be submitted.  All the work with rhodium in Chapter 4 will be submitted shortly for publication and I performed all the synthetic work. The X-ray data was collected and integrated by Joshua I. Bates and Paul W. Siu and the structures were solved and refined with the help of Joshua I. Bates, Paul W. Siu and Dr. Brian O. Patrick. Julien Dugal-Tessier, Gregory R. Dake and Derek P. Gates, to be submitted.  The synthetic work presented in Chapter 5 was performed by myself and was published in Organic Letters. The manuscript was prepared with both my supervisors Prof. Gregory R. Dake and Prof. Derek P. Gates. Megan Boyd and Doris Tang synthesized known nucleophiles used to generate compounds 5.14 and 5.15. The X-ray data was collected and integrated by Paul W. Siu and the structures solved and refined with the help of Paul W. Siu and Dr. Brian O. Patrick. Julien Dugal-Tessier, Gregory R. Dake and Derek P. Gates. Chiral Phosphaalkene– Oxazoline Ligands for the Palladium-Catalyzed Asymmetric Allylic Alkylation. Organic Letters, 2010, 12, 4667-4669.  vi TABLE OF CONTENTS  ABSTRACT .............................................................................................................................. ii PREFACE ................................................................................................................................ iv TABLE OF CONTENTS.......................................................................................................... vi LIST OF TABLES.................................................................................................................. xiii LIST OF FIGURES ..................................................................................................................xv LIST OF SCHEMES.............................................................................................................. xvii LIST OF ABBREVIATIONS AND SYMBOLS.......................................................................xx ACKNOWLEDGEMENTS ................................................................................................ xxviii DEDICATION.......................................................................................................................xxix FOREWORD..........................................................................................................................xxx CHAPTER 1 Introduction: Phosphaalkenes in Catalysis .............................................................1 1.1 Introduction...........................................................................................................................1 1.1.1 Low-Valent Phosphorus .................................................................................................2 1.2 Coordination Properties of Low-valent Phosphorus...............................................................7 1.3 Phosphaalkene Complexes ....................................................................................................9 1.4 Catalysis Using Phosphaalkene Ligands..............................................................................13 1.4.1 Introduction..................................................................................................................13 1.4.2. Ethylene Polymerization..............................................................................................13 1.4.3 Cross-Coupling Reactions ............................................................................................15 1.4.3.1 Sonogashira Reactions...........................................................................................16 1.4.3.2 Suzuki-Miyaura Reactions .....................................................................................17  vii 1.4.3.3 Stille Cross-Coupling Reactions.............................................................................18 1.4.3.4 Cyanation Reactions ..............................................................................................19 1.4.3.5 C–N Cross-Coupling Reactions .............................................................................20 1.4.4 Hydro- and Dehydro- Silylation ...................................................................................21 1.4.4.1 Dehydrogenative Silylation....................................................................................22 1.4.4.2 Hydrosilylation......................................................................................................23 1.4.5 Hydroamination and Hydroamidation...........................................................................24 1.4.5.1 Hydroamination.....................................................................................................24 1.4.5.2 Hydroamidation.....................................................................................................25 1.4.6 Isomerization................................................................................................................27 1.4.7 Allylic Substitution ......................................................................................................28 1.4.7.1 Direct Substitution of Allyl Alcohols .....................................................................28 1.4.7.2 Deallylation ...........................................................................................................32 1.4.8 Conclusion ...................................................................................................................33 1.5 Goal of the Project ..............................................................................................................33 1.6 Outline of Thesis.................................................................................................................34 CHAPTER 2 P,N-Chelate Complexes of Pd(II) and Pt(II) Based on a Phosphaalkene Motif: A Catalyst for the Overman–Claisen Rearrangement ....................................................................36 2.1 Introduction.........................................................................................................................36 2.2 Results and Discussion........................................................................................................38 2.2.1 Synthesis of Palladium(II) and Platinum(II) Complexes ...............................................38 2.2.2 Molecular Structures of 2.4 and 2.5 ..............................................................................42 2.2.3 Catalytic Activity of Complex 2.5 ................................................................................43 2.3 Summary.............................................................................................................................46  viii 2.4 Experimental Section ..........................................................................................................47 2.4.1 General Procedures.......................................................................................................47 2.4.2 Synthesis of MesPC(Ph)(2-py)PtCl2 (2.4) .....................................................................47 2.4.3 Synthesis of MesPC(Ph)(2-py)PdCl2 (2.5).....................................................................48 2.4.4 Trichloroacetimidate Formation (General Procedure) ...................................................49 2.4.5 Synthesis of 1-( l-Imino-2,2,2-trichloroethoxy)-2(E)–butene (2.6a) ..............................49 2.4.6 Synthesis of 1-(1-Imino-2,2,2-trichloroethoxy)-2(E)-hexene (2.6b) ..............................49 2.4.7 Synthesis of 1-(1-Imino-2,2,2-trichloroethoxy)-2(E)–decene (2.6c) ..............................50 2.4.8 Synthesis of 1-(1-Imino-2,2,2-trichloroethoxy)-2(E)-5-phenyl-pentene (2.6d) ..............50 2.4.9 Synthesis of 1-(1-Imino-2,2,2-trichloroethoxy)-2(E)-4-methyl-pentene (2.6e) ..............51 2.4.10 Palladium(II) Catalyzed Overman–Claisen Rearrangement (General Procedure) ........51 2.4.11 Synthesis of 2,2,2-trichloro-N-(1-methylallyl)acetamide (2.7a)...................................51 2.4.12 Synthesis of 2,2,2-trichloro-N-(1-propylallyl)acetamide (2.7b) ...................................52 2.4.13 Synthesis of 2,2,2-trichloro-N-(1-heptylallyl)acetamide (2.7c)....................................52 2.4.14 Synthesis of 2,2,2-trichloro-N-(1-(2-phenylethyl)-allyl)acetamide (2.7d)....................53 2.4.15 Synthesis of 2,2,2-trichloro-N-(1-isopropylallyl)acetamide (2.7e)...............................53 2.4.16 X-Ray Crystallography of 2.4 and 2.5.........................................................................53 CHAPTER 3 Enantiomerically Pure Phosphaalkenes: Synthesis and Polymerization ................56 3.1 Introduction.........................................................................................................................56 3.2 Results and Discussion........................................................................................................57 3.2.1 General Synthetic Strategy ...........................................................................................57 3.2.2 Preliminary Attempt at the Synthesis of Chiral Phosphaalkene .....................................59 3.2.3 Isolation of an Enantiomerically Pure Phosphaalkene ...................................................61  ix 3.3.4 Modification of the P-Aryl Group, Carbon Backbone and Electronic Properties of the PhAk–Ox Proligand ..............................................................................................................64 3.3.4.1 Modification of the Steric Properties of the P-Substituent ......................................64 3.3.4.2 Modification of the C-Substituent to Tune Bite Angle and the Electronic Properties ..........................................................................................................................................67 3.3.5 NMR Parameters of Phosphaalkene–Oxazolines ..........................................................69 3.3.6 Preliminary Polymerization Data for Phosphaalkene–Oxazoline...................................70 3.4 Conclusion ..........................................................................................................................71 3.5 Experimental Section ..........................................................................................................72 3.5.1 General Procedures.......................................................................................................72 3.5.2 Spectroscopic Data of Mixture of 3.6a and 3.6b............................................................73 3.5.3 Synthesis of (S)-PhC=OC(Me)2(CNOCH(i-Pr)CH2) (3.8) .............................................73 3.5.4 Synthesis of (S)-4-OMeC6H4C=OC(Me)2(CNOCH(i-Pr)CH2) (3.19) ............................75 3.5.5 Synthesis of (S)-2-cyclopentyl-4-isopropyl-4,5-dihydrooxazole (3.18) .........................76 3.5.6 Synthesis of (S)-PhC=OC(-C4H8-)(CNOCH(i-Pr)CH2) (3.20) .......................................77 3.5.7 Synthesis of (S)-3.5-(CF3)2C6H3C=OC(–C4H8–)(CNOCH(i-Pr)CH2) (3.21)...................78 3.5.8 Synthesis of (S)-MesP=CPhC(Me)2(CNOCH(i-Pr)CH2) (3.9a) .....................................78 3.5.9 Synthesis of (S)-2,4,6-(i-Pr)3C6H2P=CPhC(Me)2(CNOCH(i-Pr)CH2) (3.9b)..................82 3.5.10 Synthesis of 2-i-PrC6H4PCl2 (3.11) .............................................................................83 3.5.11 Synthesis of 2-t-BuC6H4PCl2 (3.13) ............................................................................84 3.5.12 Synthesis of 2-i-PrC6H4PH2 (3.14) ..............................................................................84 3.5.13 Synthesis of 2-t-BuC6H4PH2 (3.15) .............................................................................85 3.5.14 Synthesis of 2-i-PrC6H4P(SiMe3)2 (3.16).....................................................................85 3.5.15 Synthesis of 2-t-BuC6H4P(SiMe3)2 (3.17)....................................................................86  x 3.5.16 Synthesis of (S)-2-i-PrC6H4P=CPhC(Me)2(CNOCH(i-Pr)CH2) (3.9c) .........................87 3.5.17 Synthesis of (S)-2-t-BuC6H4P=CPhC(Me)2(CNOCH(i-Pr)CH2) (3.9d) ........................90 3.5.18 Synthesis of (S)-MesP=C(4-OMeC6H4)C(Me)2(CNOCH(i-Pr)CH2) (3.23a) ................91 3.5.19 Synthesis of (S)-MesP=CPhC(-C4H8-)(CNOCH(i-Pr)CH2) (3.22a)..............................94 3.5.20 Synthesis of (S)-MesP=C(3,5-(CF3)2C6H4)C(-C4H8-)(CNOCH(i-Pr)CH2) (3.24a)........97 3.5.21 X-ray Crystallography ..............................................................................................100 4.1 Introduction.......................................................................................................................102 4.2 Results and Discussion......................................................................................................104 4.2.1 Synthesis of Iridium Complexes .................................................................................104 4.2.2 Synthesis of Rhodium Complexes ..............................................................................108 4.2.3 Catalytic Activity of Rhodium Complexes..................................................................112 4.2.4 Spectroscopic Data of Rhodium and Iridium Complexes ............................................119 4.3 Conclusion ........................................................................................................................121 4.4 Experimental Section ........................................................................................................122 4.4.1 General Procedures.....................................................................................................122 4.4.2 Synthesis of MesP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Ir(C8H12)•OTf ([4.5]OTf)...........123 4.4.3 Synthesis of [MesP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Ir(C8H12)•X ([4.5]X).................126 4.4.4 Synthesis of [MesP=CPhC(Me)2(CONCH(i-Pr)CH2)]Rh(C8H12)•OTf ([4.6]OTf)........126 4.4.5 Synthesis of [MesP=CPhC(Me)2(CONCH(i-Pr)CH2)]Rh(C8H12)•BArF ([4.6]BArF).....127 4.4.6 Synthesis of [MesP=C(4-OMeC6H4)C(Me)2(CNOCH(i-Pr)CH2)]Rh(C8H12)•OTf ([4.7]OTf) ...........................................................................................................................128 4.4.7 Synthesis of [2-i-PrPhP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Rh(C8H12)•OTf ([4.8]OTf) .129 4.4.8 Synthesis of [2-i-PrPhP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Rh(C8H12)•BF4 ([4.8]BF4)...129 4.4.9 Synthesis of [2-t-BuPhP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Rh(C8H12)•OTf ([4.9]OTf) 130  xi 4.4.10 Synthesis of [2-t-BuPhP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Rh(C8H12)•BF4 ([4.9]BF4)131 4.4.11 Representative Example of Rhodium Catalyzed Allylic Alkylation...........................131 4.4.12 X-ray Crystallography ..............................................................................................132 CHAPTER 5 Chiral Phosphaalkene–Oxazoline Ligands for the Palladium-Catalyzed Asymmetric Allylic Alkylation Reactions ...............................................................................134 5.1 Introduction.......................................................................................................................134 5.2 Results and Discussion......................................................................................................137 5.2.1 Synthesis of Complex [5.1]OTf and 5.2......................................................................137 5.2.2 Catalytic Activity of Palladium Complexes [5.1]OTf and [5.7]OTf ............................139 5.2.3 Scope of Palladium Catalyzed Allylic Substitution with [5.7]OTf...............................144 5.3 Summary...........................................................................................................................145 5.4 Experimental Section ........................................................................................................145 5.4.1 General Procedures.....................................................................................................145 5.4.2 Synthesis of (S)-2,4-diisopropyl-5,5-dimethyl-4,5-dihydrooxazole (5.4).....................146 5.4.3 Synthesis of (S)-2-(4-isopropyl-5,5-dimethyl-4,5-dihydrooxazol-2-yl)-2-methyl-1- phenylpropan-1-one (5.5)....................................................................................................147 5.4.4 Synthesis of MesP=CPhCMe2(CNOCH(i-Pr)CMe2) (5.6)...........................................148 5.4.5 Synthesis MesP=CPhCMe2(CNOCH(i-Pr)CH2)PdCl2 (5.2) .........................................149 5.4.6 Synthesis of MesP=CPhCMe2(CNOCH(i-Pr)CMe2)PdCl2 (5.8)...................................150 5.4.7 Synthesis of MesP=CPhCMe2(CNOCH(i-Pr)CH2)PdC3H5⋅OTf ([5.1]OTf) .................150 5.4.8 Synthesis of MesP=CPhCMe2(CNOCH(i-Pr)CMe2)PdC3H5⋅OTf ([5.7]OTf) ...............151 5.4.9 Representative Procedure for Allylic Alkylation. Synthesis of (S,E)-dimethyl 2-(1,3- diphenylallyl)malonate (5.9) ...............................................................................................152 5.4.10 Synthesis of (S,E)-diethyl 2-(1,3-diphenylallyl)malonate (5.10)................................153  xii 5.4.11 Synthesis of (S,E)-dibenzyl 2-(1,3-diphenylallyl)malonate (5.11) .............................153 5.4.12 Synthesis (R,E)-dimethyl 2-(1,3diphenylallyl)-2-methylmalonate (5.12)...................153 5.4.13 Synthesis (S,E)-3-(1,3-diphenylallyl)pentane-2,4-dione (5.13)..................................154 5.4.14 Synthesis of (E)-dimethyl 2-(2-(benzyloxy)ethyl)-2-(1,3-diphenylallyl)malonate (5.14) ...........................................................................................................................................154 5.4.15 Synthesis of (E)-dimethyl 2-(2-((tert-butyldimethylsilyl)oxy)ethyl)-2-(1,3- diphenylallyl)malonate (5.15) .............................................................................................155 5.4.16 Synthesis of (R,E)-dimethyl 2-allyl-2-(1,3-diphenylallyl)malonate (5.16).................156 5.4.17 Synthesis of (R,E)-dimethyl 2-(but-3-en-1-yl)-2-(1,3diphenylallyl)malonate (5.17) ..156 5.4.18 Synthesis of (R)-dimethyl 2-phenylcyclopent-3-ene-1,1-dicarboxylate (5.18) ...........157 5.4.19 Synthesis of (R)-dimethyl 2-phenylcyclohex-3-ene-1,1-dicarboxylate (5.19) ............158 5.4.20 X-ray Crystallography ..............................................................................................158 CHAPTER 6 Summary and Future Work................................................................................160 6.1 Summary...........................................................................................................................160 6.2 Future Work......................................................................................................................163 6.3 Concluding Remarks.........................................................................................................165 REFERENCES .......................................................................................................................167   xiii LIST OF TABLES Table 1.1 Sonogashira Cross Coupling Reactions with Phosphaalkene Ligands........................17 Table 1.2 Suzuki Cross Coupling Reactions with Phosphaalkene Complexes. ..........................18 Table 2.1 Results of the Aza-Claisen Rearrangement Using 2b as a Catalyst. ...........................46 Table 2.2 X-ray Crystallographic Data for 2.4 and 2.5..............................................................55 Table 3.1 31P{1H} and 13C{1H} NMR Chemical Shifts of Chiral Phosphaalkenes......................70 Table 3.2 COSY Data for Compound 3.8. ................................................................................74 Table 3.3 NMR Data for Compound 3.8. ..................................................................................75 Table 3.4 COSY Correlation for Compound 3.9a. ....................................................................80 Table 3.5 NMR Data for 3.9a. ..................................................................................................81 Table 3.6 COSY Correlation for Compound 3.9c......................................................................88 Table 3.7 NMR Data for Compound 3.9c. ................................................................................89 Table 3.8 COSY Correlation for Compound 3.23a. ..................................................................92 Table 3.9 NMR Data for Compound 3.23a. ..............................................................................93 Table 3.10 COSY Correlation for Compound 3.22a. ................................................................95 Table 3.11 NMR Data for Compound 3.22a. ............................................................................96 Table 3.12 COSY Correlation for Compound 3.24a. ................................................................98 Table 3.13 NMR Data for Compound 3.24a. ............................................................................99 Table 3.14 X-ray Data Collection and Refinement Details......................................................101 Table 4.1 31P{1H} and 13C{1H} NMR Shifts of Rhodium and Iridium Complexes. ..................120 Table 4.2 COSY Correlation for Compound [4.5]OTf ............................................................124 Table 4.3 NMR Data for Compound [4.5]OTf. .......................................................................125  xiv Table 4.4 Data Collection and Refinement Details of Complexes [4.5]OTf, [4.6]OTf, and [4.8]BF4. .................................................................................................................................133 Table 5.1 Initial Results Using PhAk–Ox Pd Complexes [5.1]X and [5.7]X in Asymmetric Allylic Alkylation. ..................................................................................................................140 Table 5.2 Data Collection and Refinement Details for 5.2 and 5.8. .........................................159   xv LIST OF FIGURES Figure 1.1 Sample of Commercially-Available Chiral Ligands...................................................2 Figure 1.2 Motifs Incorporating P=C Bonds. ..............................................................................3 Figure 1.3 Strategy for P=C Bond Stabilization..........................................................................4 Figure 1.4 First Examples of Phosphaalkenes.............................................................................4 Figure 1.5 Reactivity of P=C Bonds. ..........................................................................................6 Figure 1.6 General Synthesis of Phosphaalkenes. .......................................................................7 Figure 1.7 Coordination Modes of Phosphaalkenes. ...................................................................8 Figure 1.8 Molecular Orbital Depiction of Carbonyl, Phosphaalkene and Imine Ligands............9 Figure 1.9 Molecular Orbital Representation of Phosphaalkenes Binding to Metals....................9 Figure 1.10 Phosphaalkene Complexes Used as Ethylene Polymerization Catalysts. ................14 Figure 1.11 Ligands and Complexes Used in the Sonogashira and Suzuki Coupling.................16 Figure 1.12 Products of Hydroamination Using 1.26 by Ozawa................................................25 Figure 2.1 Ligands Containing Low Valent Phosphorus. ..........................................................36 Figure 2.2 31P{1H} NMR (121 MHz, CDCl3) of 2.4 (δ = 206, 1JPtP = 4486 Hz)..........................39 Figure 2.3 Molecular Structure of 2.4 (50% Probability Ellipsoids). .........................................40 Figure 2.4 31P{1H} NMR (121 MHz, CDCl3) Spectrum of 2.5 (δ = 230). ..................................41 Figure 2.5 Molecular Structure of 2.5 (50% Probability Ellipsoids). .........................................42 Figure 2.6 General Mechanism for the Metal Catalyzed Overman–Claisen Rearrangement. .....44 Figure 3.1 Molecular Structure of 3.6a (50% Probability Ellipsoids). .......................................60 Figure 3.2 Molecular Structure of 3.9a (50% Probability Ellipsoids). .......................................63 Figure 3.3 Variety of Phosphaalkene–Oxazoline Proligands.....................................................69 Figure 3.4 31P{1H}(121 MHz, CH2Cl2) NMR Spectrum of Polymer 3.25. .................................71  xvi Figure 4.1 31P{1H}NMR (121 MHz, THF) Spectrum of [4.5]OTf. ..........................................105 Figure 4.2 Molecular Structure of [4.5]OTf (50% Probability Ellipsoids). ..............................107 Figure 4.3 31P{1H} NMR (121 MHz, CDCl3) Spectrum of [4.6]OTf. ......................................109 Figure 4.4 Molecular Structure of [4.6]OTf (50% Probability Ellipsoids). ..............................111 Figure 4.5 Postulated Mechanism of Rhodium Catalyzed Allylic Alkylation..........................113 Figure 4.6 Pictographic Representation of PhAk–Ox Ligands Coordinated to Rhodium. ........115 Figure 4.7 Molecular Structure of [4.8]BF4 (25% Probability Ellipsoids)................................117 Figure 4.8 Postulated Mechanism of Stereospecific Pathway of Rhodium Catalyzed Allylic Alkylation...............................................................................................................................118 Figure 5.1 Structure of PHOX and PhAk–Ox Proligands........................................................135 Figure 5.2 Molecular Structure of 5.2 (50% Probability Ellipsoids). .......................................139 Figure 5.3 Molecular Structures Showing the Three Conformations of 5.8 in the Solid State: (a) 40%, (b) 37%, (c) 23% (50% probability ellipsoids)................................................................143 Figure 5.4 Preliminary Investigation of the Scope of Enantioselective Allylic Alkylation Using PhAk–Ox Catalyst [5.7]OTf Indicating Functional Group Tolerance.......................................144 Figure 6.1 New Phosphaalkene Proligands. ............................................................................163 Figure 6.2 Diphenyl Allyl Palladium PhAk–Ox Complex.......................................................164   xvii LIST OF SCHEMES Scheme 1.1 Isomerization and Complexation of Phosphaalkene Ligand 1.1..............................10 Scheme 1.2 Synthesis of DPCB ligands ....................................................................................11 Scheme 1.3 π-Conjugation of DPCB Pt(alkyne) Complexes .....................................................12 Scheme 1.4 Distorted Trigonal Monopyramidal Fe(I) Phosphaalkene Complex........................12 Scheme 1.5 Stille Coupling Using Ligand 1.22 by Yoshifuji.....................................................19 Scheme 1.6 Scope of the Cyanation of Aryl Bromides with 1.23 by Yoshifuji ..........................20 Scheme 1.7 Buchwald-Hartwig Coupling Using 1.23 by Yoshifuji ...........................................21 Scheme 1.8 Ullman Coupling Using 1.22 by Yoshifuji. ............................................................21 Scheme 1.9 Dehydrogenative Silylation of Ketones Using 1.24 by Ozawa................................22 Scheme 1.10 Ozawa’s Proposed Mechanism of Dehydrogenative Silylation.............................23 Scheme 1.11 Z-Selective Hydrosilylation of Alkynes by Ozawa. ..............................................24 Scheme 1.12 Hydroamination of 1,3 Dienes by Ozawa.............................................................25 Scheme 1.13 Conjugate Addition Benzyl Carbamate to Enones Using 1.27 by Ozawa..............26 Scheme 1.14 Conjugate Addition of Benzyl Carbamate to Enones Using 1.28 by Ozawa .........27 Scheme 1.15 Gold Catalyzed Cycloisomerization of Alkynes and Enynes by Ito ......................28 Scheme 1.16 Allylic Alkylation of Allyl Alcohols using 1.26 by Ozawa...................................29 Scheme 1.17 Ozawa’s Proposed Substitution Mechanism.........................................................29 Scheme 1.18 Ozawa’s Proposed Mechanism of the C–O Cleavage Step ...................................30 Scheme 1.19 Le Floch Allylic Alkylation Mechanism ..............................................................31 Scheme 1.20 Cyclodehydration Using 1.26 by Ozawa ..............................................................32 Scheme 1.21 Deallylation Reactions Using 1.26 by Ozawa.......................................................33 Scheme 2.1 Strategy for Our P,N-Ligand..................................................................................37  xviii Scheme 2.2 Base-Catalyzed Phospha-Peterson to Generate Pyridyl-Phosphaalkene. .................37 Scheme 2.3 Route to Bis(trimethylsilyl)phosphine 2.1. .............................................................38 Scheme 2.4 Formation of Platinum Complex 2.4. .....................................................................39 Scheme 2.5 Formation of Palladium Complex 2.5. ...................................................................41 Scheme 2.7 General Overman–Claisen Rearrangement.............................................................44 Scheme 2.8 General Method for the Generation of Linear Allylic Alcohols. .............................45 Scheme 3.1 Complex of a L-Menthol Substituted Phosphaalkene..............................................57 Scheme 3.2 General Synthetic Strategy to Access Phosphaalkenes. ..........................................58 Scheme 3.3 Initial Investigation Towards Enantiomerically Pure Phosphaalkenes. ...................60 Scheme 3.4 Synthesis of Enantiomerically Pure Phosphaalkene Precursor. ...............................61 Scheme 3.5 Synthesis of an Enantiomerically Pure Phosphaalkene. ..........................................62 Scheme 3.6 Synthesis of 2-RC6H4P(SiMe3)2 (R = i-Pr; R = t-Bu). .............................................66 Scheme 3.7 Modification of the P-Substituent. .........................................................................66 Scheme 3.8 Modification of the of PhAk–Ox Proligand’s Carbon Framework. .........................68 Scheme 4.1 Synthesis of 1-Phosphaethenyl-2-phosphanylferrocenes and Its Catalytic Activitity. ...............................................................................................................................................103 Scheme 4.2 Iridium Cyclooctadiene Complexes of Ligand 3.9a..............................................104 Scheme 4.3 Rhodium Cyclooctadiene Complexes of Ligands 3.9a. ........................................109 Scheme 4.4 Rhodium Catalyzed Allylic Alkylation Using Rhodium Complex [4.6]OTf. ........114 Scheme 4.5 Synthesis of [4.7]OTf and its Activity in Allylic Alkylation.................................114 Scheme 4.6 Rhodium Complexes of Phosphaalkene Ligand 3.9c and 3.9d..............................116 Scheme 4.7 Kinetic Resolution of Allyl Carbonates Using [4.6]OTf.......................................119 Scheme 5.1 Postulated Generalized Mechanism for Allylic Alkylation.132...............................136 Scheme 5.2 Desymmetrization of π-Allyl Systems.225 .............................................................136  xix Scheme 5.3 Rationale for the Enantiodescriminating Step.225 ..................................................137 Scheme 5.4 Synthesis of Palladium Complexes of 3.9a. .........................................................138 Scheme 5.5 Synthesis of Phosphaalkene 5.6 and Complex [5.7]OTf. ......................................141 Scheme 5.6 Synthesis of complex 5.8. ....................................................................................142 Scheme 5.7 Ring Closing Metathesis of 5.16 and 5.17. ...........................................................145 Scheme 6.1 Overman–Claisen Rearrangement with 2.5. .........................................................160 Scheme 6.2 Synthesis of Enantiomerically Pure Phosphaalkene–Oxazoline. ...........................161 Scheme 6.3 Synthesis of Rhodium Complexes and their Activity in Allylic Alkylation. .........162 Scheme 6.4 Palladium Catalyzed Allylic Alkylation Using a PhAk–Ox Ligand. .....................162 Scheme 6.5 Catalytic Reactions to Investigate the Use of PhAk–Ox Proligands......................165   xx LIST OF ABBREVIATIONS AND SYMBOLS [α]Dt     specific rotation at temperature t and wavelength of sodium D line α     regiochemical descriptor Å     angstrom (1 × 10-10 meters) Ac     acetyl Ar     aryl anal.     analysis (combustion analysis) av     average β     regiochemical descriptor BArF     tetrakis[3,5-bis(trifluoromethyl)phenyl]borate box     bisoxazoline br     broad or broadened (spectra) BSA     N,O-bis(trimethylsilyl)acetamide Bu     butyl m-CPBA    m-chloroperoxybenzoic acid c     centi (10-2) c     concentration (g/100 mL) in optical rotation ºC     degrees Celsius ca.     circa, about calcd     calculated cat     catalytic Cbz     carbobenzyloxy cf.     compare  xxi cod     cyclooctadiene (ligand) compd     compound COSY     correlation spectroscopy crys     crystal Cy     cyclohexyl or C6H12– δ     chemical shift in parts per million (ppm) δ+, δ–     partial positive charge, partial negative charge ∆     heat      difference ∆δ     difference in chemical shift (spectroscopy) d     doublet (NMR spectroscopy)      day(s) d     type of orbital D     deuterium dba     dibenzylideneacetone DBU     1,8-dizabicyclo[5.4.0]undec-7-ene DCC     dicyclohexylcarbodiimide deg     degree DFT     density functional theory DMAP     4-dimethylaminopyridine DMF     N,N-dimethylformamide DIBAl-H    diisobutylaluminum hydride DPCB     diphosphinidenecyclobutene E     entgegen (configuration)  xxii Ea     activation energy ed., eds.    edition, editions Ed., Eds.    editor, editors ee     enantiomeric excess e.g.     example EI     electron impact EPR     electron paramagnetic resonance equiv     equivalents ESI     electron spray ionization Et     Ethyl or CH3CH2– EtOAc     ethyl acetate etc.     and so forth eV     electronvolt Fc     ferrocene FMO     frontier molecular orbital g     gram      gas gem     geminal GOF     goodness of fit GPC     gel permeation chromatography {1H}     proton decoupled (NMR spectroscopy) η     hapto h     hour Hep     heptyl (C7H16–)  xxiii HMBC    heteronuclear multiple bond correlation HMQC    1H-detected heteronuclear multiple quantum coherence HOBt     1-hydroxybenzotriazole HOMO    highest occupied molecular orbital HPLC     high-pressure liquid chromatography HRMS     high-resolution mass spectrometry Hz     hertz i     iso (as in i-Pr) I     intensity init.     initiator int     internal (X-ray) IR     infrared IMes     N,N’-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene J     coupling constant (NMR spectroscopy) k     kilo K     kelvin Kα     spectral line kgf     kilogram-force L     absolute configuration L     liter      ligand L     large LDA     lithium diisopropylamide LG     leaving group  xxiv lit.     literature LRMS     low resolution mass spectrometry LUMO    lowest unoccupied molecular orbital µ     absorption coefficient (X-ray) µn     bridging ligand (n = number of metals bridging) m     meta m     multiplet (NMR spectroscopy)      milli (10-3) M     metal      mega (106)      parent mass      molar (moles per liter) M     medium m/z     mass-to-charge ratio Me     methyl or CH3– MeLi     methyllithium or CH3Li Mes     2,4,6-trimethylphenyl Mes*     2,4,6-tri-tert-butylphenyl min     minute(s) mmHg     millimeters of mercury Mn     number-average molecular weight mol     mole(s) mp     melting point Mw     weight-average molecular weight n     normal (in n-butyl)      total number of units  xxv Naph     naphthalene NBO     natural bond orbitals NMP     N-methyl-2-pyrrolidone NMR     nuclear magnetic resonance No.     number NR     not reported Nu     nucleophile o     ortho [O]     oxidant ORTEP    Oak ridge thermal ellipsoid plot OTf     trifluoromethanesulfonate Ox     oxazoline π     type of orbital π*     type of anti-bonding orbital %     percent (parts per hundred) p     type of orbital param     parameter PDI     polydispersity index (Mw/Mn) Ph     phenyl PhMe     toluene PhAk–Ox    phosphaalkene–oxazoline (proligand or ligand) PHOX     phosphinooxazoline (proligand or ligand) PPM     parts per million PPV     poly(phenylene vinylenes)  xxvi Pr     propyl py     pyridine (ligand) or C5H5N, or pyridyl Py     pyridine or C5H5N or pyridyl q     quartet (NMR spectroscopy) Q     quaternary quint     quintet (NMR spectroscopy) R     generic substituent      residual factor (X-ray) R     rectus (configurational) refln     reflection rt     room temperature σ     background (X-ray) s     type of orbital      secondary ( as in s-Bu) S     sinister (configurational) S     small SCE     saturated calomel electrode sept     septuplet (NMR spectroscopy) SN2’     second-order nucleophilic allylic substitution SFC     supercritical fluid chromatography SFU     Simon Fraser University syst     system θ     angle t     temperature (degrees Celcius) T     temperature (in Kelvin)  xxvii THF     tetrahydrofuran TMEDA    N,N,N’,N’-tetramethylethylenediamine TMS     trimethylsilyl TOF     turn over frequency trans     stereochemical descriptor triple detection GPC   gel permeation chromatography with light scattering      instrument, viscometer and differential refractometer UBC     University of British Columbia UV     ultraviolet V     volt w     weighted X     halide, counterion or leaving group Z     zusammen (configurational)      number of units in a cell (X-ray crystallography)  xxviii ACKNOWLEDGEMENTS  I would like to thank first both my supervisors, in alphabetical order, Prof. Gregory Dake and Prof. Derek Gates, for giving me the wonderful opportunity to work in both their labs. I am also grateful for their wisdom, their patience and their dedication to this project.  I would like to thank members of the Dake group and Gates group, Erik, Mandy, Paul H., Tyler, Leah, Kevin, Bronwyn, Vittorio, Krystle, Cindy, Jenny, Jen, Josh, Paul S., Emmanuel, Amber, Jiazhang, Ivo, Eamonn, Spencer, Andrew, Ben, and all former summer and 449 students for their presence and their help.  I would also like to thank the NMR, Mass Spec, and UBC shops and services for their work in keeping the equipment functioning throughout the years. I would also like to particularly thank Josh, Paul S. and Dr. Brian O. Patrick for X-ray crystallographic data help. I also want to acknowledge financial support from NSERC, Gladys Estella Laird Fellowship and UBC. I am also grateful for the Britton (SFU) and Sammis lab for access to their chiral analytic instruments.  I would also like to mention the contribution of late Prof. Keith Fagnou for whose influence was instrumental in my choice to pursue a career in chemistry.  Special thanks go to Brian, Bichler, Lauren, Meryn and Josh for their friendship, advice and especially for good times during my studies. I cannot thank enough Jenny, my fiancée, whose patience and support was invaluable throughout my studies. I am looking forward to the rest of my life with you. Finally and not least I would also like to thank my parents, Christiane and Pierre, for all their help over the years, without their support I would not of been able to get here. I am also grateful to my little sister and brother, Delphie and Etienne, whose presence growing up has toughened me up for the grind of graduate school.  xxix DEDICATION À ma mère (Christiane) et à mon père (Pierre)  xxx FOREWORD Both carbon and phosphorus are main group elements, but the studies of these elements belong to two different fields of chemistry: organic and inorganic, respectively. Interestingly, the chemistry of low-valent phosphorus and carbon is surprisingly similar — phosphorus has been dubbed the “carbon copy”. Advances in low-valent phosphorus chemistry have relied heavily on adapting methodologies developed for organic chemistry, reinforcing their relationship. Despite the fact that low-valent phosphorus compounds have been studies for approximately half a century, until recently, they have received limited attention for applications in materials, organometallic and organic chemistry. This dissertation discusses the use of phosphaalkenes in organic synthesis, specifically the applications of these species as ligands in transition metal mediated reactions. The synthesis of these compounds pushed the limits of current inorganic synthetic methodologies. The work discussed in this dissertation was selected to highlight the progress and advances in the field of phosphaalkene chemistry. The work presented in Chapters 3, 4 and 5 appear to be in chronological order. However, in reality the investigations occurred concurrently. Some compounds synthesized in Chapter 3 were driven by results obtained in Chapter 4 and Chapter 5.  A few comments are required regarding the numbering of compounds found in this dissertation. Two numbers are used to name compounds: the first number refers to the chapter where this compound first appears and the second is the sequential order where it appears within a chapter. For example, the third numbered compound in Chapter 2 is 2.3 and does not change throughout the manuscript. In Chapter 1 and Chapter 2 generic compounds or equations are referred with capitals letters such as A, B, C, etc. In Chapter 2, 4 and 5 mechanistic details of catalytic cycles or intermediates are numbered using roman numerals I, II, etc. Throughout the  xxxi dissertation the use of small letters (a, b, c, etc) after the number indicates a relation between the compounds in questions. Not all compounds are numbered, some simple organic and inorganic compounds are referred simply by name or structural formula.  Other than in Chapter 1 and Chapter 6, the dissertation is written in manuscript style, with an expanded introduction for the general readership of this dissertation. The stylistic and formatting requirements of this document follow the 3rd edition of The ACS Style Guide.  1 CHAPTER 1 Introduction: Phosphaalkenes in Catalysis 1.1 Introduction  Synthetic organic chemistry has been revolutionized by the advances in transition metal catalysis and by extension, ligand design.1-3 Much of this success has been due to the development of ligands designed to support transition metal mediated catalysis. The uses of these catalytic methods have become inescapable in many carbon–carbon bond forming reactions. Indeed, the importance was recognized by awarding the 2010 Nobel Prize to Heck, Negishi and Suzuki for the development of these types of catalytic methods. Although initial discoveries and innovations were carried out using systems coordinated to triphenylphosphine, improvements and expansions of these synthetic methods were made possible through adjustments of the techniques using tailored phosphorus ligands.4-6 The close relationship between the metal centre and its ligands has led to development of chiral ligands for the purpose of transferring chiral information from the ligand to the products of the catalytic reaction. In many applications, such as medicinally active compounds, only one enantiomer is desired and obtaining enantiomerically pure products is an important challenge in organic chemistry. The significance of asymmetric catalysis was highlighted in the awarding of the Nobel Prize to Knowles, Noyori and Sharpless in 2001 for their pioneering work. Even if great success in this field has been achieved, industrial applications are dominated by a single reaction class, hydrogenation.7,8,9 Clearly, applying other asymmetric organic transformations are desirable and the development of new chiral ligands continues to be an active area of research.10 Phosphorus is ubiquitous in ligands. The majority of these phosphorus-based ligands (phosphines, phosphites, phosphonites) contain phosphorus in the parent tetrahedral geometry (formally sp3 hybridized). Examples of some commercially available chiral ligands containing  2 tetrahedral phosphorus are shown in Figure 1.1. In comparison, ligands incorporating low-valent phosphorus in a parent trigonal planar geometry (formally sp2 hybridized), have barely been investigated.11 The further development of such ligands could provide opportunities for discovering novel reactivity of the corresponding ligand-metal complexes with applications in inorganic chemistry, materials science and organic chemistry. A short introduction to the chemistry and chemical properties of low-valent phosphorus compounds is necessary as this thesis topic involves the development of these compounds as ligands. PPh2 PPh2 BINAP P P Me Me Me Me Me-DuPHOS N O PPh2 PHOX N PPh2 Quinap P P Ph o-Tolyl o-Tolyl Ph DiPAMP monophos Chiraphite Trost NH NH PPh2 O O PPh2 O O P N MeMe O O PP O O t-Bu t-Bu MeO MeO O O t-Bu OMe t-Bu OMe Josiphos Fe PCy2 PPh2 Me PPh2 PPh2Me Chiraphos N N P P Me t-Bu t-Bu Me QuinoxP* Figure 1.1 Sample of Commercially-Available Chiral Ligands.  1.1.1 Low-Valent Phosphorus Compounds incorporating P=C bonds are divided into two general classes. The first class of compounds incorporates the P=C bond into a cyclic structure, such as the phosphinines, phosphaferrocenes and phospholides (Figure 1.2). The second class, the phosphaalkenes, have a P=C bond in an acyclic setting (Figure 1.2).12 Low-valent phosphorus compounds are highly reactive and can be difficult to isolate due to problems of dimerization, oligomerization or  3 polymerization. They can be stabilized using a number of strategies. The incorporation of the P=C bond into an aromatic system provides an electronic stabilization (i.e. phosphinines, phosphaferrocenes and phospholides in Figure 1.2). The P=C bond can also be protected from dimerization, oligomerization or polymerization reactions through placing large substituents on the phosphorus and/or carbon atoms, which is often the case for phosphaalkenes. For example, the bulky supermesityl group (Mes* = 2,4,6-(t-Bu)3C6H2) is often employed as a phosphorus substituent to kinetically stabilize a phosphaalkene through steric protection.13 P C H H Mes* P phosphaalkenesphosphinines P Fe phosphaferrocenes P aromatic stabilization P phospholides steric stabilization Mes*= t-Bu t-Bu t-Bu  Figure 1.2 Motifs Incorporating P=C Bonds.  Depictions illustrating the electronic and steric stabilization of P=C bonds in regards to polymerization are shown in Figure 1.3. P=C bonds within a delocalized system have electronic stability resulting in unfavorable energy profiles for polymerization, which imparts thermodynamic stability. Bulkier molecules tend to have a higher activation (Ea) barrier for polymerization, which results in kinetic stability. Experimentally it has been observed that phosphaalkene stability is sensitive to the steric properties of the phosphorus atom substituent.13  4 P C P C e n e rg y reaction coordinate Ea e n e rg y reaction coordinate thermodynamic stability (delocalization) !G P C R RR P C R P C R R R n n n n n P C n P C n kinetic stability (steric) Figure 1.3 Strategy for P=C Bond Stabilization.  Initial attempts to synthesize phosphaalkenes and other low-valent phosphorus compounds were often plagued by decomposition products, an observation which illustrates the importance of the stabilization described above.14 These products were often described as polymeric type materials, which were poorly characterized. In 1976, Becker reported the first isolable phosphaalkene (Figure 1.4).15 That same year Kroto and Nixon characterized the unstable phosphaethylene molecule using microwave spectroscopy.16 Two years later, the first all-carbon substituted phosphaalkene was isolated by Bickelhaupt.17 These three seminal papers laid the groundwork for the future of phosphaalkene chemistry. C P OTMS Ph Becker 1976 P C Mes Ph Ph Bickelhaupt 1978 P C H HH Kroto and Nixon 1976 Figure 1.4 First Examples of Acyclic Phosphaalkenes.14-16  There are roughly 200 isolable phosphaalkenes that have been reported in the chemical literature to date, and they have similar properties. The P=C bond length within a phosphaalkene  5 is between 1.63 Å and 1.71 Å, and features a C–P=C dihedral angle (θ) between 100º and 107º.18 The P=C bond is comprised of a (3sp2–2sp2) σ bond and a (3p–2p) π bond between the phosphorus and carbon atoms. The P=C bond is relatively apolar because of the small electronegativity difference between carbon (2.5, Pauling) and phosphorus (2.1, Pauling), and because phosphorus is electropositive in the σ component of the P=C bond but electronegative in the π-component.19,20 As a result, the P=C bond can be normally polarized P(δ+)–C(δ–) or inversely polarized P(δ–)–C(δ+) depending on the substitution pattern.21 Investigation of the frontier molecular orbitals (FMOs) of the P=C bond reveals striking similarities to the FMOs found in a C=C bond.22 UV photo-electron spectroscopy of phosphaethylene and ethylene revealed that the HOMO is the π bond in both compounds and that they have similar energies (−10.5 eV for the C=C π bond and −10.3 eV for the P=C π bond, respectively).22 Significantly, the phosphorus lone pair in phosphaethylene is only slightly lower in energy than the π bond (−10.7 eV), which has implications in metal binding, and is discussed later.22 The similarity of the P=C bond to the C=C bond has led to phosphorus being dubbed the “carbon copy”.12,13 The general reaction classes of phosphaalkenes have been reviewed in detail.12-14,18,23-26 The following examples of the reactivity of the P=C bond in phosphaalkenes serve to illustrate the analogy between the P=C and C=C bonds (Figure 1.5). Phosphaalkenes can undergo cycloadditions and other sigmatropic rearrangements (reaction A). They can undergo additions of H–X across the P=C bond to produce regioisomeric products (reaction B). The P=C bond of phosphaalkenes can undergo addition polymerization generating inorganic polymers (reaction C). Metals can bind phosphaalkenes through the phosphorus lone pair or the P=C π bond (reaction D) as a consequence of the relatively small energy difference between both orbitals. Finally, phosphaalkenes may also be hydrogenated (reaction E) or epoxidized (reaction F) if the phosphorus lone pair is coordinated to a metal.  6 P C [Rh], H2 P C HH [M] [O] P C O[M] H2C CH2H2C P C CH2 [M] P C [M] HX P C P C X X HH or + P C [M] init. P C n A B C D EF  Figure 1.5 Reactivity of P=C Bonds.  The P=C/C=C bond analogy can be extended to the synthesis of phosphaalkenes, as these compounds are synthesized using similar strategies as the ones employed for the synthesis of alkenes (Figure 1.6). Construction of P=C bonds can be achieved by the elimination of H–X (reaction G),17,27-37 by a 1,3-silyl transfer (Brook-type rearrangement, reaction H) known as the Becker route,15,38-51 by base catalyzed isomerization (reaction I),52-54 by a phospha-Wittig reaction (reaction J),55-62 by the transfer of a metal phosphinidene (Tebbe-type olefination, reaction K),63- 66 and finally, by a phospha-Peterson reaction (reaction L).67-77 All the phosphaalkenes described in this thesis were synthesized using one of two variations of the phospha-Peterson reaction, and these are discussed in more detail in Chapter 2, 3 and 5. A base catalyzed reaction was used in the synthesis of compounds in Chapter 2 and a classical stoichiometric activation method was employed in Chapter 3 and 5.  7 P CP C HCl DBU COP P Ph Ph Ph -HCl + + CO base COP MLn+ P SiMe3 SiMe3 + O C Cl P C H CH2 base (cat) P SiMe3 SiMe3 G H I J L K  Figure 1.6 General Synthesis of Phosphaalkenes.  1.2 Coordination Properties of Low-valent Phosphorus Phosphorus in the sp2 hybridized form (i.e. phosphaalkenes) has different binding properties than traditional sp3 hybridized phosphines. Information on the coordination chemistry of phosphinines, phosphaferrocenes and phospholides can be found in several review papers.11,78- 80 The focus of this dissertation section is the metal binding properties of phosphaalkenes. Five different coordination modes are possible in phosphaalkenes due to the presence of a phosphorus lone pair and a π bond (Figure 1.7). The most common metal binding motif reported for phosphaalkenes is η1(P)-coordination (M).81 The second most common motif is η2(P,C)-coordination (N). Due to the small energy difference between the lone pair and the π bond, a phosphaalkene can interconvert between η1- and η2-coordination.82 The preference for η1-coordination over η2 is not always predictable, although it has been observed that electron- rich metals with relatively little steric bulk are more likely to bind in η2 fashion.80 More exotic coordination modes can sometimes be observed (Figure 1.7, O, P, Q). η1, η2-Coordination has been reported when an excess of metal is present (O).81,83 Another unusual mode is η1, (µ2-P)-  8 coordination due to the capacity of phosphorus to become tetravalent (P).81,84 Phosphaalkenes incorporated into a metal cluster have led to the characterization of the very unusual η1, η2, µ3- binding mode (Q).85 Only η1-coordination was observed in the work described and therefore only its electronic properties will be discussed in detail. [M] P C R2 R3 R1 [M] !1(P) P C R2 R3 R1 [M] !1, !2 [M] P C R2 R3 R1 !2(P,C) P C R2 R3 R1 [M] [M] !1, (µ2"P) P C R2 R3 R1 !1,!2, µ3 [M] [M] [M] M N O P Q Figure 1.7 Coordination Modes of Phosphaalkenes.80  A depiction of the orbitals involved in η1-coordination shows a resemblance between phosphaalkenes and carbon monoxide when they act as ligands (Figure 1.8).86 The similarities of phosphaalkene ligands to carbonyl ligands is due to a low lying π* orbital with the proper symmetry for back-donation. The phosphorus lone pair in phosphaalkenes is weakly donating since it has 64% s character according to calculations.11 In contrast to the earlier description of phosphaalkenes as parent trigonal planar, which alluded to sp2 phosphorus, these calculations suggest a significant deviation from idealized sp2 hybridization. These calculations are also consistent with the observed structures of phosphaalkenes, which contain a C–P=C dihedral angle (ca. 100º to 107º) due to the high p character of the σ bonds. In contrast, imines, the lighter congener of phosphaalkenes, have a lone pair with much lower s character (39%) and a π* that does not properly overlap for metal back-donation (Figure 1.8).11 The difference in s character  9 between the phosphorus and the nitrogen lone pair is because heavier main group elements do not hybridize to the same extent as their lighter congeners.87-89 To summarize, phosphaalkene ligands can be viewed as poor σ donors and good π acceptors. P CC O N C poor ! acceptorstrong ! acceptor P C C N 100º 117º 39% 2s 61% 2p 66% 3s 34% 3p strong ! donorpoor ! donorstrong ! acceptor Figure 1.8 Molecular Orbital Depiction of Carbonyl, Phosphaalkene and Imine Ligands.  Phosphaalkenes bind to metals in the following fashion (Figure 1.9): the phosphorus lone pair donates into an empty metal d orbital and a filled metal d orbital can back-donate into the π* orbital of the P=C bond. Upon metal binding, phosphaalkenes become closer to the ideal sp2 hybridized geometry, which can be observed by an increase of the C–P=C angle to around 115º. P C 115ºM PM P C C M  Figure 1.9 Molecular Orbital Depiction of Phosphaalkenes Binding to Metals.  1.3 Phosphaalkene Complexes This section illustrates a few selected examples of phosphaalkene coordination complexes rather than discuss all of them exhaustively. Geoffroy has shown that all three EE-, EZ- and ZZ-isomers of a phosphaalkene ligand 1.1 are present in solution (Scheme 1.1).90,91 The equilibrium is facile at room temperature in the presence of ambient light.90,91 Only EE 1.1  10 contains the proper geometry for metal coordination and the pincer complex 1.2 was formed after ortho metalation with (PhCN)2PdCl2 or (MeCN)2PtCl2. The electrochemical properties of 1.1 and 1.2 were studied.90,91 A quasi-reversible electrochemical reduction of the free ligand EE 1.1 occurs at –1.89 V/SCE. The quasi-reversible electrochemical reductions of complexes 1.2 (M = Pd and Pt) are between –0.92 and –1.29 V/SCE. EPR studies of the reduced complexes showed that the reduction is a ligand-centered process and that a significant portion of the unpaired electron is located on the P=C bond atoms.90 These experiments indicate that phosphaalkene ligands can be actor ligands and not only spectator ligands. This can have implication in their use in catalysis.92 C C P Mes* P Mes* M = Pd M = Pt H H C C P Mes* H P Mes* H C C P H P Mes* H Mes* EE 1.1 EZ 1.1 ZZ 1.1 C C P Mes* P Mes* H H M Cl 1.2 Scheme 1.1 Isomerization and Complexation of Phosphaalkene Ligand 1.1.90,91  The diphosphinidenecyclobutene (DPCB) compounds are an important class of phosphaalkene ligands and thus their preparation is discussed in this section in addition to an example of their metal-complexes (Scheme 1.2).93 The synthesis of DPCBs start with the reaction of PCl3 with dimethylamine to generate PCl(NMe)2. Two P–Cl bonds are replaced with amino groups to ensure mono-addition of alkynyl lithium (RC≡CLi) species in the following  11 step. After addition of the alkyne, the amino groups can be removed by treatment with anhydrous HCl(g) to reintroduce the chlorides (RC≡CPCl2). Subsequent addition of Mes*Li generates chlorophosphine 1.3 that is dimerized using Zn or t-BuLi to produce compound 1.4. A thermal Claisen-type rearrangement generates unstable phosphaallene 1.5 that spontaneously electrocyclizes to DPCBs. A variety of different R groups such as aryls, silyl, alkyl and heteroaryls, have been introduced using this synthetic strategy. R P Mes* Cl Zn or t-BuLi R C C R P PMes* Mes* C C R R P PMes* Mes* 1.3 1.5DPCB PCl3 Me2NH PCl(NMe2)2 RC CLi1) 2) HCl(g) RC CPCl2 Mes*Li P P R R Mes* Mes* 1.4 !  Scheme 1.2 Synthesis of DPCB ligands.93  Platinum(0) DPCB alkyne complexes (1.6) have interesting conjugative properties (Scheme 1.3).94 Modification to the electronic properties of the tolan (Ar–C≡C-Ar) ligand resulted in a color change. Upon increasing the electron-rich nature of the alkyne, complexes of type 1.6 change in color from reddish orange (1.6a) to dark red (1.6b) to mulberry (1.6c) and finally to teal (1.6d). DFT calculations revealed that the π-accepting nature of the phosphaalkene ligand generates an extended π-conjugated system that has HOMO-LUMO gaps within the visible region of the electromagnetic spectrum.95 This phenomenon has not observed with other ligands for similar Pt(alkyne) complexes.  12 C C P P Mes* Mes* R R (cod)Pt C C P P Mes* Mes* R R Pt a R = CO2Me b R = Ph c R = 4-(MeO)C6H4 d R = 4-(Me2N)C6H4 1.6a-d  Scheme 1.3 π-Conjugation of DPCB Pt(alkyne) Complexes.95  Recently, a 15-electron iron phosphaalkene complex 1.9 was isolated and observed by X- ray crystallography (Scheme 1.4).96 The Fe(I) centre was found to be in the rare distorted trigonal monopyramidal geometry. Complex 1.9 was prepared by coordination of FeBr3 to 1.7 followed by one electron reduction of Fe(II) complex 1.8. Analysis of the bonding properties by NBO analysis revealed an effective dπ-pπ metal-phosphaalkene interaction due to the low-lying π* orbital of the phosphaalkene ligand. The strong π-accepting properties of the ligand were proposed to be responsible for stabilizing the high-spin Fe(I) complex in the unusual geometry. NC Ph P C Ph P Mes* Mes* FeBr3 NC Ph P C Ph P Mes* Mes*Fe BrBr KC8 NC Ph P C Ph P Mes* Mes*Fe Br 1.8 1.91.7 Scheme 1.4 Distorted Trigonal Monopyramidal Fe(I) Phosphaalkene Complex.96  In summary, these selected examples serve to illustrate the strong π accepting properties of phosphaalkene ligands in coordination chemistry.11 These ligands have stabilized metals in unusual geometries,96 have increased conjugative properties94 and have undergone electrochemical processes.91 Novel coordination chemistry can yield fruitful and exciting reactivity in catalysis.  13  1.4 Catalysis Using Phosphaalkene Ligands 1.4.1 Introduction Over the past 15 years there has been growing interest to incorporate phosphaalkenes in transition metal catalysis.11,79 The first known report of a catalytic transformation to use a phosphaalkene ligand was a Sonogashira coupling in 1995 (Chapter 1.4.3). No other examples however were reported until the year 2000. While this new area of research is growing, the field of phosphaalkene ligand remains unexplored compared with phosphine ligands. The following section is a comprehensive survey of the use of phosphaalkene ligands in catalysis, although some recent work is discussed in the relevant dissertation chapter. The sub-sections of Chapter 1.4 are divided by reaction class: ethylene polymerization (Chapter 1.4.2), followed by cross- coupling (Chapter 1.4.3), hydro- and dehydro- silylation (Chapter 1.4.4), hydroamination and hydroamidation (Chapter 1.4.5), cycloisomerization (Chapter 1.4.6) and allylic substitution (Chapter 1.4.7).  1.4.2. Ethylene Polymerization Phosphaalkene ligands were investigated for ethylene polymerization because they resemble the successful α-diimine ligands in structure (replacing P with N in 1.13 and 1.15).97 Phosphaalkene-based ligands (1.10-1.15) are active in ethylene polymerization and are more stable than α-diimine ligands.  14 C C R R P PMes* Mes* Pd Me Me C S H P Pd Mes* Me NCMe B(3,5-(CF3)2C6H3)4 1.10 R = Ar 1.11 R = SiMe3 1.12 R = H C C H H P PMes* Mes* Ni B(3,5-(CF3)2C6H3)4 Ar C N Me P Pd Mes* Me NCMe B(3,5-(CF3)2C6H3)4 Ar Ph 1.13 1.14 1.15 R R  Figure 1.10 Phosphaalkene Complexes Used as Ethylene Polymerization Catalysts.77,98-100  Ozawa and coworkers reported neutral DPCB palladium complexes 1.10-1.12 that are active in ethylene polymerization upon acid activation [H(OEt2)2BArF] to the cationic complexes. Precatalyst 1.10 (Ar = Ph) was more active than precatalyst 1.11 and 1.12 and polymerized [128 kg⋅h-1⋅(mol cat)-1] ethylene with a pressure of 10 kgf⋅cm-2, generating polymers with molecular weights of 18.7 kg⋅mol-1 and polydispersity indexes (PDI) of 14.8. These phosphaalkene complexes polymerized ethylene at 100 ºC, a temperature that decomposed α-diimine catalysts.98 Further studies on the electronic properties of DPCB ligands found generally that electron withdrawing aryl groups were more active (Ar = 4-MeOC6H4 < Ar = Ph < Ar = 3,5-(CF3)2C6H3 < Ar = 4-(CF)3C6H4). The most active precatalyst 1.10 (Ar = 4-(CF)3C6H4) gave the best results with an activity of 210 kg⋅h–1⋅(mol cat)-1 and molecular weights of 43 kg⋅mol-1 and PDIs of 23.7.99 Brookhart and coworkers synthesized a mixed P,N-catalyst 1.13 (Ar = Mes) that catalyzed ethylene polymerization slowly, turnover frequency (TOF) of 94 h-1, than α-diimine ligands (TOF of 4500 h-1).77 The slow TOF was attributed to slow ethylene migratory insertion and calculations of the energy barrier found that this was indeed the case. A P,S-phosphaalkene complex 1.14 (Ar = 2,4,6-(i-Pr)C6H2, R = H) was synthesized to lower the migratory insertion  15 energy barrier and it was found to have comparable activity (TOF of 4300 h-1) to α-diimine ligands. Catalyst 1.14 (Ar = 2,4,6-(i-Pr)C6H2, R = H) also has greater stability (TOF of 3000 h-1 after 15 h) for the polymerization conditions than α-diimine ligands, but generated polymers of low molecular weight (Mn = 215 g/mol). Modification of the ligand structure by the addition of a methyl group to the backbone generated a catalyst [1.14 (Ar = 2,4,6-(i-Pr)C6H2, R = Me)] that had high activity (TOF 3100 h-1). The ethylene polymers generated were of high molecular weights (Mn = 2300-2500 g/mol) but also had high levels of branching. Ionkin and Marshall also investigated the use of phosphaalkene ligands for ethylene polymerization. Nickel complex 1.15 gave ethylene polymers (Mw = 57 591 g/mol with a PDI of 3.19) with less branching and better thermal stability compared with α-diimine nickel catalysts.100 Overall, phosphaalkene based molecules have greater stability in palladium and nickel catalyzed polymerization of ethylene, which is an advantage for industrial applications.  1.4.3 Cross-Coupling Reactions Phosphaalkene ligands were also investigated in cross-coupling reactions since these reactions are well established and offer a useful benchmark for catalytic activity.101 Phosphaalkene based ligands are active in a variety of different cross-coupling reactions such as Sonogashira,102 Suzuki-Miyaura,103 Stille,104 Buchwald-Hartwig105,106 and Ullmann107 couplings. The complexes shown in Figure 1.11 are active in the Sonogashira and Suzuki-Miyaura coupling.  16 C C Ph Ph P PMes* Mes* Pd Cl Cl P C Mes* Me PPh2 S Cl2Pd P C Mes* Me PR2 O Cl2Pd Pd PP CC Mes* H H MeO OMe Mes* OTf C C P H P H Mes* Mes* Pd Cl 1.16 1.191.18 1.20 1.2 P C Mes* Me PPh2Cl2Pd 1.17 P PMes* Mes* n S S Pd Cl Cl 1.21 [CH2) (CH2)7  Figure 1.11 Ligands and Complexes Used in the Sonogashira and Suzuki Coupling.108-114  1.4.3.1 Sonogashira Reactions The complexes shown in Figure 1.11 are all active in the Sonogashira cross-coupling reaction (Table 1.1). Yoshifuji and coworkers were the first to use a phosphaalkene ligand in catalysis. Complex 1.16 was shown to couple 1-bromo-4-nitrobenzene with trimethylsilylacetylene in 77% yield (entry 1).108 Years later, the same research group developed a more active 1,3-diphosphapropene complex 1.17 to catalyze the coupling of phenylacetylene and iodobenzene in high yields (entry 2 and 3). However, some limitations of complex 1.17 were noted as it was unable to couple 1-bromo-4-nitrobenzene and it was sensitive to air and moisture.109 To remedy the sensitivity of 1.17, an oxidized complex 1.18 was synthesized but it afforded the cross-coupled product in lower yields (entry 4).110 More electron rich phosphine sulfide complex 1.19 generated diphenylacetylene in synthetically useful yields and it could tolerate the presence of moisture and air (entry 5).111 Complex 1.19 did not cross-couple bromobenzene with phenylacetylene but instead dimerized phenylacetylene quantitatively to diphenylbutadiyene ((Ph–C≡C–C≡C–Ph).112 The authors of this work suggest that the  17 dimerization product is the result of a dialkynylpalladium(II) complex formed during the reaction. Le Floch and coworkers found that monodentate phosphaalkene complex 1.20 and tridentate phosphaalkene complex 1.2 were effective at the coupling of bromoarenes with phenylacetylene with low catalyst loadings (entry 7-12).113 Yoshifuji and coworkers successfully incorporated a phosphaalkene complex into a polymer backbone 1.21. The polymer complex was active for the cross-coupling of 1-bromo-4-nitrobenzene and trimethylsilylacetylene and the catalyst could easily be removed from the crude reaction mixture and recycled (entry 13).114 Table 1.1 Sonogashira Cross-Coupling Reactions with Phosphaalkene Ligands. + Ar-XR R Ar [Pd], CuX, base solvent entry [Pd] [Pd] (mol %) R Ar-X base/solvent yield (%) Ref 1 1.16 2 SiMe3 4-(NO2)-C6H4-Br Et2NH 77 108 2 1.17 2.5 Ph Ph-I Et3N 99 109 3 1.17 2.5 SiMe3 Ph-I Et3N 93 109 4 1.18 2.5 Ph Ph-I Et3N 68 110 5 1.19 2.5 Ph Ph-I Et3N 83 111 6 1.19 2.5 Ph 4-(MeO)-C6H4-I Et3N 65 111 7 1.20 0.1 Ph Ph-Br Et3N/PhMe 85 113 8 1.2 0.1 Ph Ph-Br Et3N/PhMe 78 113 9 1.20/1.2 0.1 Ph 4-(MeCO)-C6H4-Br Et3N/PhMe 95 113 10 1.2 0.1 Ph 4-(MeO)-C6H4-Br Et3N/PhMe 40 113 11 1.2 0.1 Ph 4-(Me)-C6H4Br Et3N/PhMe 76 113 12 1.20 0.1 Ph 3,5-(Me)2-C6H3Br Et3N/PhMe 78 113 13 1.21 NR Ph 4-(NO2)-C6H4Br Et3N/DMF 83 114  1.4.3.2 Suzuki-Miyaura Reactions The coupling of aryl halides with aryl boronic acids was also performed with phosphaalkene complexes 1.18, 1.19, 1.2 and 1.20 (Figure 1.11). The coupling of aryl halides and aryl boronic acids or esters is an important class of C–C bond forming reactions that has many applications.103 Phosphine oxide complex 1.18 efficiently cross-coupled iodobenzene and phenylboronic acid (Table 1.2, entry 1).110 More electron rich phosphine sulfide complex 1.19 was very efficient for the same cross-coupling reaction (entry 2) but could not be extended to the  18 use of bromobenzene or 4-iodoanisole.111 Very low loadings of complexes 1.20 and 1.2 were required for the activation of bromoarenes for cross-coupling with phenylboronic acid (entry 3- 8).113 Table 1.2 Suzuki Cross-Coupling Reactions with Phosphaalkene Complexes. + Ar1-X [Pd], K2CO3 Ar1ArAr-B(OH)2 solvent entry [Pd] [Pd] mol % Ar-B(OH)2 Ar1-X yield (%) solvent ref 1 1.18 4 Ph Ph-I 71 THF 110 2 1.19 4 Ph Ph-I 99 THF 111 3 1.20 1 × 10-5 Ph Ph-Br 99 PhMe 113 4 1.2 1 × 10-5 Ph Ph-Br 88 PhMe 113 5 1.2 1 × 10-5 Ph 4-(MeCO)-C6H4-Br 54 PhMe 113 6 1.20 1 × 10-5 Ph 4-(MeO)-C6H4-Br 99 PhMe 113 7 1.20 1 × 10-5 Ph 4-MeC6H4-Br 99 PhMe 113 8 1.20 1 × 10-5 Ph 3,5-(Me)2-C6H3-Br 99 PhMe 113  1.4.3.3 Stille Cross-Coupling Reactions In the above reviewed work, the complexes used for catalysis were preformed and isolated but in the following example the catalyst was generated in situ. Addition of ligand 1.22 and Pd(OAc)2 was efficient at the Stille cross-coupling reaction of aryl bromides with vinyl-, allyl- and aryl- tins (Scheme 1.5).115 The cross-coupling conditions were general for a variety of different bromoarenes containing a variety of different electronic and steric properties. The cross-coupling reactions also tolerated the presence of unprotected alcohols and heteroaromatics.   19 C C Ph Ph P PMes* Mes* 1.22 Br + SnBu3 2 mol % 1.22/Pd(OAc)2 CsF, dioxane, 100 ºC R R R R R R = Ph 99% R = 2-MeC6H4 42% R = 4-t-BuC6H4 99% R = 4-MeOC6H4 99% R = 4-(COMe)C6H4 80% R = 2-(CH2OH)C6H4 97% R = 2-C4H3S 80% R = 2-MeC4H2S 98% R = Ph 98% R = 2-MeC6H4 68% R = 4-t-BuC6H4 91% R = 4-MeOC6H4 96% R = Ph 98% R = 2-MeC6H4 92% R = 4-MeC6H4 93% R = 4-t-BuC6H4 91% R = 4-MeOC6H4 99% R = 4-NO2C6H4 91% R = 2-(COMe)C6H4 80% R = 4-(CO2Et)C6H4 91% R = 2-C5H4N 97% R = 2-C4H3S 82% SnBu3 or  Scheme 1.5 Stille Coupling Using Ligand 1.22 by Yoshifuji.115  1.4.3.4 Cyanation Reactions The cyanation of aryl bromides is another reaction that was effectively catalyzed by generating the metal complex in situ. Addition of Pd2(dba)3 with 1.22 in the presence of Zn and Zn(CN)2 effectively catalyzed the cyanation of aryl bromides at 100 ºC (Scheme 1.6).116 The catalysts loading of 2 mol % each of palladium and 1.22 is low for cyanations reactions that are normally plagued by the deactivation of palladium by cyanides.117 Experimentally, it was previously found that the addition of Zn dust is an important additive to reduce catalyst loadings.118 The yields obtained for the reaction were generally high and were used to synthesize the bulky 2,4,6-trimethylbenzonitrile in synthetically useful yields.    20 C C Ph Ph P PMes* Mes* 1.22 Ar Br Ar CN 1.22 (2 mol %), Pd2(dba)3  (1 mol %) Zn(CN)2, Zn, NMP 100 ºC CN R R CN CN 83% R = NMe2 41% R = OMe 85% R = t-Bu 94% R = Me 76% R = CHO 74% R = COMe 68% R = CO2Me 88% R = NO2 92% R = CN 80% R = Cl 35% R = Et 50% R = CH2Br 60% R = OMe 68%  Scheme 1.6 Scope of the Cyanation of Aryl Bromides with 1.23 by Yoshifuji.116  1.4.3.5 C–N Cross-Coupling Reactions Anilines were coupled to bromoarenes (Buchwald-Hartwig coupling) using palladium allyl complex 1.23 and potassium tert-butoxide in synthetically useful yields (Scheme 1.7).119 It is noteworthy that the amination proceeds at room temperature without solvent. Monosubstitution of the aniline is the only observed product at room temperature even in the presence of excess bromobenzene. Disubstitution of aniline with two equivalents of bromobenzene and the cross-coupling of secondary aromatic amines such as N-methyl aniline were both performed at 100 ºC. In contrast, aliphatic secondary amines such as piperidine and morpholine coupled readily at room temperature.  21 C C Ph Ph P PMes* Mes* Pd OTf 1.23 Ar Br + H N R1 H t-BuOK Ar N R1 H N H R1 R N H Ph N H Ph N H Ph OMe 78% 97% N MePh N Ph Ph N O N N 70% 76% 55% 70% 51% 1.23 (2 mol %) R1 = Ph 98% R1 = Ph(CH2)2 82% R1 = 4-MeC6H4CH2 80% R1 = !-NaphCH2 69% R1 = PhCHMe 60% R1 = CH3(CH2)15 62% R1 = 4-MeOC6H4 99% R = OMe 63% R = OCO2Et 95% R = t-Bu 97% R = Br 71%  Scheme 1.7 Buchwald-Hartwig Coupling Using 1.23 by Yoshifuji.119  Aryl bromides and chlorides were also coupled with anilines (Ullman coupling) in the presence of proligand 1.22, copper iodide and potassium tert-butoxide (Scheme 1.8).120 The isolated yields obtained in the copper catalyzed cross-coupling of anilines were very similar to the ones catalyzed by palladium complex 1.23 (Scheme 1.7) but required temperatures of 100 ºC. Ar X + H N R1 R2 t-BuOK, 100 ºC Ar N R1 R2 1.22 (2 mol %)/CuI (2 mol %) C C Ph Ph P PMes* Mes* 1.22 X = Br or Cl Scheme 1.8 Ullman Coupling Using 1.22 by Yoshifuji.120  1.4.4 Hydro- and Dehydro- Silylation This section discusses the use of phosphaalkene ligands in reactions with silanes. Two types of reactions have been catalyzed by phosphaalkene-based ligands to date:  22 dehydrosilylation of ketones (Chapter 1.4.4.1) and Z-selective hydrosilylation of alkynes (Chapter 1.4.4.2).  1.4.4.1 Dehydrogenative Silylation In the presence of silanes, transition metal catalysts typically react with ketones to reduce the C=O bond and generate silyl ethers.121 Instead, the dehydrosilylation of ketones to silyl enol ethers was observed using complex 1.24 (Ar = Ph) (Scheme 1.9).122 Up to 15% of the reduced C=O product was isolated when changes to the electronics properties of 1.24 (Ar = 4-MeOC6H4 or Ar = 4-(CF3)C6H4) were tested. The reactions were performed without solvent, favored the formation of the most substituted silyl enol ether, and gave predominantly the E-olefin geometry. C C Ar Ar P PMes* Mes* Pt Me OTf R1 O R2 + HSiMe2Ph (3 mol %) Py (3 mol %), 50 ºC R1 OSiMe2Ph + H2 OSiMe2Ph OSiMe2Ph OSiMe2Ph OSiMe2Ph OSiMe2Ph PhMe2SiO 100% 100% 89 : 11 100% 75% OSiMe2Ph OSiMe2Ph OSiMe2Ph 89% 92% 83 : 17 100% 1.24 OSiMe2Ph MeO 69% R2 1.24  Scheme 1.9 Dehydrogenative Silylation of Ketones Using 1.24 by Ozawa.122  It was proposed that the π-accepting properties of the DPCB ligand in 1.24 were responsible for the selectivity of ketone dehydrosilylation over hydrosilylation.122 The proposed mechanism is illustrated in Scheme 1.10. The π-accepting properties of the DPCB ligand favor  23 the formation of metal enolates that can subsequently be hydrosilylated to silyl enol ethers and palladium hydrides (Scheme 1.10). Expulsion of dihydrogen from an acid-base reaction regenerates the palladium complex and the base leading to an overall dehydrosilylation process. R1 O R2 R1 R2 OPdLn R1 R2 OSiR'3 PdLn + base  base•H + HPdLn H2 HSiR'3  Scheme 1.10 Ozawa’s Proposed Mechanism of Dehydrogenative Silylation.122  1.4.4.2 Hydrosilylation In general, the hydrosilylation of alkynes by a metal catalyst will generate preferentially the E-vinyl silane. 121 Ruthenium dimer complex 1.25 (Ar = 4-MeOC6H4) however, is selective for the formation of the Z-vinyl silane (Scheme 1.11).123 Terminal alkynes with either electron donating or withdrawing aryl groups, as well as aliphatic groups, were hydrosilylated in high yields. The low catalyst loading and short reaction times were also noteworthy features of using 1.25 (Ar = 4-MeOC6H4). Mechanistic studies of the reaction indicated that the strong π-accepting properties of 1.25 (Ar = 4-MeOC6H4) were responsible for the Z-selectivity.123 Complex 1.25 (Ar = 4-MeOC6H4) outperformed all other catalysts to generate bifunctional Z-vinyl silanes en route to all-cis poly(phenylene vinylenes) (PPVs).124   24 C C Ar Ar P P Ru Mes* Mes* Cl Cl CO 2 (0.25-1 mol %) R + HSiMe2Ph R SiMe2Ph R SiMe2Ph R SiMe2Ph + + CH2Cl2 or PhMe, 10-300 min 1.25 R = Ph (98:1:1 (100%)) R = 4-MeOC6H4 (99:1:0 (100%)) R = 4-CF3C6H4 (97:1:2 (100%)) R = n-C6H13 (97:1:2 (100%)) Scheme 1.11 Z-Selective Hydrosilylation of Alkynes by Ozawa.123  1.4.5 Hydroamination and Hydroamidation This section discusses the use of palladium and rhodium phosphaalkene complexes in the formal addition of N–H across dienes and enones.125 The first set of examples are of a palladium catalyzed hydroamination of 1,3 dienes and the second set of examples are of a rhodium and a palladium catalyzed hydroamidation of enones.  1.4.5.1 Hydroamination Palladium allyl DPCB complexes 1.23, 1.26 and 1.27 are efficient at the 1,4- hydroamination of 1,3-dienes with aniline (Scheme 1.12).126 A solvent effect was observed in the hydroamination reaction between polar and non-polar solvents. For example, toluene (non-polar) gave high yields (91%) and no reaction was observed for DMF (polar) (equation R). The electronic nature of the DPCB ligand was also investigated and it was found that lower yields are obtained with more electron withdrawing groups on the DPCB ligand, 1.27 (58%) < 1.23 (89%) < 1.26 (91%). Styrene exclusively gave the 1,2-branched hydroamination product (equation S).  25 C C Ar Ar P PMes* Mes* Pd OTf 1.23   Ar = Ph 1.26   Ar = 4-MeOC6H4 1.27   Ar = 4-CF3C6H4 + H2NPh + H2NPh NHPh N Ph H (1-3 mol %) rt, 5 h 1.26 (2 mol %) PhMe, 100 ºC, 10 h (R) (S)  Scheme 1.12 Hydroamination of 1,3 Dienes by Ozawa.126  Investigation of the substrate scope showed a trend in 1,2-addition over 1,4-addition (Figure 1.12). 1,2-Addition was favored for monosubstituted terminal dienes and 1,4-addition was predominant for disubstituted terminal dienes. Both 1,2- and 1,4-addition gave the branched and the more substituted alkene products.126 n-C6H13 n-C6H13 NHPh n-C6H13 NHPh 8:2 80% Ph Ph 92% NHPh NHPh 93:7 85% 1,2 addition 1,4 addition NHPh PhHN 88:12 92% NHPh 96% NHPh 68% NHPh substrate product substrate product  Figure 1.12 Products of Hydroamination Using 1.26 by Ozawa.126  1.4.5.2 Hydroamidation P,N,P complex 1.27 is active in the conjugative addition of carbamates to enones (Scheme 1.13) in excellent yields without solvent.127 The addition of silver triflate (AgOTf) is  26 essential for catalytic activity. Exchange of the chloride counter ion in 1.27 with a triflate counter ion did not generate an active catalyst without further addition of a catalytic amount AgOTf. Control experiments showed that AgOTf by itself was not a competent catalyst for conjugate addition and the presence of 1.27 was also required. NC C P H P H Mes* Mes* Rh ClO + CbzNH2 AgOTf (4 mol %), no solvent O NHCbz >98% 99% 95% 1.27 2 mol % Ph OO NHCbzNHCbz  Scheme 1.13 Conjugate Addition Benzyl Carbamate to Enones Using 1.27 by Ozawa.127  Dicationic complex 1.28 is also an active catalyst in the conjugate addition of carbamates to enones (Scheme 1.14).128 Dicationic complex 1.28 is more active than neutral complex PdCl2(MeCN)2 but has comparable activity to the dicationic complex [Pd(MeCN)4](BF4)2. The disproportionation of cyclohexenone to cyclohexanone and phenol is sometimes observed when palladium black is generated from [Pd(MeCN)4](BF4)2.128 An advantage of using 1.28 is that no palladium black is formed during the reaction.128   27 Ph OO NHCbzNHCbz C C Ph Ph P PMes* Mes* Pd MeCN NCMe 2+ 2 OTf 1.28     (1 mol %) O + CbzNH2 O NHCbzPhMe, rt, 30-120 min 92% 79% 75% Ph O NHCbz 87% Scheme 1.14 Conjugate Addition of Benzyl Carbamate to Enones Using 1.28 by Ozawa.128  1.4.6 Isomerization In large part, catalysis with phosphaalkene ligands has used transition metals from the first and second rows. The following example of gold catalyzed cycloisomerization of enynes129 has expanded the use of phosphaalkene ligands to the third row of the transition metals. Chlorogold complexes 1.29, E-1.30, Z-1.30 and 1.31 catalyzed the isomerization of enynes to cyclopentenes in high yields (Scheme 1.15, reaction T).130 Interestingly, the phosphaalkene-gold complexes did not require the addition of a silver co-catalyst as is often the case for these types of reactions. The cycloisomerizations of alkynes with esters or carboxylic acids using 1.29 (reaction U) and E-1.30 (reaction V) were performed under basic conditions to generate lactones in high yields. The addition of methanol to the reaction mixture trapped the cationic intermediate generating an exo-methylene moiety in quantitative yield (W).131 Phosphaalkene-gold complexes showed potent catalytic activity in gold catalyzed cycloisomerization reactions.  28 P C Mes* Me MeAu Cl P C Mes* CH2Ph MeAu Cl P C Mes* Me CH2PhAu Cl 1.29 E-1.30 Z-1.30 R R MeO2C MeO2C 1.29, E-1.30, Z-1.30 MeO2C MeO2C R R R = Me (quant) R = H (63-76%) 1.29 CH2Cl2, 20 ºC or ClCH2CH2Cl, 70 ºC Py, THF 20 ºC, 24 h CO2H PhCH2 O PhCH2 O MeO2C MeO2C E-1.30 Py, THF 20 ºC, 24 h O O O O (92%) (84%) MeO2C MeO2C 1.31 MeO2C MeO2C (quant) CH2Cl2, MeOH 24 h C C Ph Ph P PMes* Mes* 1.31 Au Au Cl Cl MeO (T) (U) (W)(V)  Scheme 1.15 Gold Catalyzed Cycloisomerization of Alkynes and Enynes by Ito.130,131  1.4.7 Allylic Substitution Allylic substitution is an important method for the construction of C–C, C–O and C–N bonds.132 Phosphaalkene complexes 1.26 and 1.33 can catalyze the substitution of allylic alcohols directly with nucleophiles (Chapter 1.4.7.1). Mechanistic studies of complex 1.26 in the substitution reaction have permitted the discovery of other ligands with similar reactivity. Phosphaalkene complex 1.26 was used in the deallylation of a variety of allyl ethers and esters with better selectivity than traditional palladium catalysts (Chapter 1.4.7.2). 1.4.7.1 Direct Substitution of Allyl Alcohols Allyl alcohols usually must be converted to allyl acetates before allylic substitution can take place.132 The direct substitution of allylic alcohols is more efficient by removing the alcohol conversion step. Complexes 1.23 (91%), 1.26 (96%), 1.27 (82%) and 1.32 (63%) were effective at directly substituting allyl alcohols with aniline (Scheme 1.16).111,112,133 The best results were  29 obtained with electron rich complex 1.26, which was then subsequently used for substrate scope investigation. The expected regiochemistry for palladium catalyzed allylic substitution was observed with the nucleophile adding at the least sterically hindered carbon. No erosion of the enantioselectivity was observed when an enantioenriched allyl alcohol was used. The authors of this work proposed a catalytic cycle between palladium hydride 1.33 and palladium allyl complex 1.26 (Scheme 1.17). C C Ar Ar P PMes* Mes* Pd OTf 1.23   Ar = Ph 1.26   Ar = 4-MeOC6H4 1.27   Ar = 4-CF3C6H4 P C Mes* Me PPh2 S Pd 1.32 OTf R OH + NucH (0.1 mol %) NucR R NHPh R OEt OO COMe CO2Et 95% 1.26 PhMe, rt Ph OH (0.1 mol %) PhNH2 (2 equiv) PhMe, rt, 3 h Ph NHPh 92% (98.5% ee) 1.26 (98.5% ee) R = H 96% R = Me 85% R = H 92% R = Ph 85% R = C3H7 96% R = C3H7 93% R = Ph 90%  Scheme 1.16 Allylic Alkylation of Allyl Alcohols using 1.26 by Ozawa.111,112,133  (DPCB)Pd OTf H OH H2O PhNH2NHPh (DCPB)Pd OTf 1.261.33 Scheme 1.17 Ozawa’s Proposed Substitution Mechanism.133  Ozawa and coworkers performed more detailed mechanistic studies of the C–O bond cleavage step. They proposed that the π-acidic nature of the DPCB ligands generates a more acidic palladium hydride species 1.33 (Scheme 1.18). Complexation of 1.33 with an allyl alcohol reversibly generates Pd(II) species 1.34 followed by 1.35. The properties of the DPCB ligand  30 favor the formation of 1.35 that upon elimination of water regenerates complex 1.26 (Scheme 1.18). The success of 1.26 over 1.27 and 1.24 was rationalized as a careful balance of donor/acceptor properties of the DPCB ligand. The π acidic nature of the DPCB ligand enhances the rate of the rate limiting C–O cleavage step and the electron donating nature of the methoxy group of 1.26 stabilizes palladium hydride species 1.33.134 (DPCB)Pd OTf H 1.33 OH OH(DPCB)Pd H OTf 1.34 OH2(DPCB)Pd OTf 1.35 -H2O (DCPB)Pd OTf 1.26 PhNH2 NHPh  Scheme 1.18 Ozawa’s Proposed Mechanism of the C–O Cleavage Step.134  Interested in the reactivity of DPCB ligands in the direct allylic substitution reaction, Le Floch and coworkers proposed an alternative metal hydride free mechanism. Using DFT calculations, the proposed mechanism is lower in energy and resembles the accepted mechanism for allylic substitutions (Scheme 1.19).135 Nucleophilic attack of the palladium allyl complex does not differ in both mechanisms. However, Le Floch and coworkers proposed that the dissociation of Pd-alkene complex 1.37 is rate-limiting. The 14 valence electron Pd(0) complex 1.38 is thought to be stabilized by the strong π-accepting properties of the DPCB ligand. Coordination of this reactive intermediate with an allyl alcohol generates alkene complex 1.39. Complex 1.40 would be generated by an unusual intermolecular protonation of 1.39 with an allyl ammonium species. Elimination of water would regenerate complex 1.36. To verify their working catalytic proposal Le Floch and coworkers predicted computationally that  31 triphenylphosphite would be a good ligand for this transformation. Experimentally, the triphenylphosphite catalyst had similar activity as 1.26, which reinforces the mechanism postulated by Le Floch and coworkers. However, both mechanisms proposed are plausible by the calculations advanced by Le Floch and co-workers (Scheme 1.17 and 1.19). More studies are required to elucidate the mechanism of the direct substitution of allyl alcohols using DPCB 1.26. P Pd P P Pd P O P Pd P MeH2N P Pd PP Pd P HO H NHMe H 1.36 1.37 1.38 1.39 1.40 MeNH2 HO H2O MeHN MeH2N  Scheme 1.19 Le Floch Allylic Alkylation Mechanism.135  Expanding on the direct substitution of allyl alcohols, a cyclodehydration of cis-2-butene- 1,4-diols was utilized to synthesize dihydrofurans (Scheme 1.20).136 The reactions were performed by mixing the diol and β-dicarbonyls with a catalytic amount of base and 1.26 in toluene at 100 ºC. Acetyl acetone and ethyl acetoacetate generated dihydrofurans in synthetically useful yields (91% and 74%, respectively). Benzoyl acetone gave 2:1 mixture of structural isomers and the use of diphenylpropanedione gave a 47% yield of cyclized product.  32 C C Ar Ar P PMes* Mes* Pd OTf 1.26   Ar = 4-MeOC6H4 HO OH + O O O Me COMe1.26 (2 mol %) Py (10 mol %) PhMe, 100 ºC 91% O Me CO2Et O Me COPh O Ph COMe O Ph COPh 74% 2:1 75% 47%  Scheme 1.20 Cyclodehydration Using 1.26 by Ozawa.136  1.4.7.2 Deallylation Complex 1.26 is also an effective catalyst in the deallylation of a variety of allylic phenol ethers in the presence of aniline (Scheme 1.21 equation X). Deallylation reactions were performed in air and in the presence of a variety of different functionalities such as vinyl, alkynyl, hydroxy, acetoxy, silyloxy, and acetyl groups.137 Interesting selectivity was observed when the deallylation of hydroxybenzoic acid derivatives was studied (equation Y and Z). Complex 1.26 selectively removed only one allyl group when two were present in the molecule. The allyl ether group was deprotected with a 2-hydroxybenzoic acid derivative (equation Y) but the allyl ester was deallylated for 3- and 4-hydroxybenzoic acid derivatives (equation Z). In all cases the deprotection of both position was observed when Pd(PPh3)4 was used as a deallylation catalyst. The authors of the work speculate that coordination effects are responsible for the observed selectivities.  33 C C Ar Ar P PMes* Mes* Pd OTf 1.26   Ar = 4-MeOC6H4 1.26 (0.1 mol %) PhNH2, 30 ºCY O Y OH Y = H, CN, CHO, CO2Me, CH2OH, CH(OH)Me, COMe, Br NHPh O O O 1.26 (0.1 mol %) PhNH2, 30 ºC OH O O 99% O O 1.26 (0.1 mol %) PhNH2, 30 ºC OH O 92% O O (X) (Y) (Z)  Scheme 1.21 Deallylation Reactions Using 1.26 by Ozawa.137  1.4.8 Conclusion Transition-metal complexes containing phosphaalkene ligands catalyze a variety of reactions, in some cases with previously unobserved reactivity. The majority of the work on incorporating phosphaalkenes in catalysis has been done with the DPCB ligand set. Even today, there are a limited number of successful different phosphaalkene motifs that have been used in catalysis. The synthesis, isolation, and poor stability of phosphaalkenes remain challenges for their widespread use in catalysis. Their unique donor-acceptor properties can fill an important gap in ligand design. For these reasons, their study is a worthy endeavor.  1.5 Goal of the Project In general, the goal of my project was to synthesize novel phosphaalkenes that could be applied in catalysis. A survey of the literature yielded areas of investigation that could yield new breakthroughs in phosphaalkene ligand design. The phosphaalkene ligands being used in  34 catalysis were all achiral and they all incorporated the sterically bulky Mes* group. The use of smaller P-substituent was an area that required investigation because using smaller P-substituent would make phosphaalkene more accessible. Most of the work presented in this introductory section was performed with the DPCB ligands, which are P,P-chelating ligands. The investigation of P,N-chelating phosphaalkene ligands had received much less attention. The initial short term goal of my project was the feasibility of using a P,N-chelate phosphaalkene ligand bearing a smaller P-substituent. This initial goal also had the secondary purpose of exposing me to the manipulation of phosphaalkenes. This would prepare me to attack the main goal of my project: the design, the synthesis, the coordination chemistry and the application of an enantiomerically pure phosphaalkene ligand in organic chemistry. A phosphaalkene for this purpose was never reported and this would fill an important gap in phosphaalkene ligand design.  1.6 Outline of Thesis The outline of the dissertation will roughly map into a chronological order of events. Chapter 2 expands on initial work on an achiral pyridyl phosphaalkene bearing the smaller P- Mes substituent. Its coordination chemistry and its catalytic activity in a sigmatropic rearrangement (Overman–Claisen rearrangement) are discussed. Chapter 3 discusses the synthetic strategy and the design of a general synthetic route to enantiomerically pure phosphaalkenes. Following my work on the synthesis of enantiomerically pure phosphaalkenes, their coordination to rhodium and iridium are discussed in Chapter 4. This chapter discusses as well preliminary studies into the catalytic activity of these phosphaalkene ligands in rhodium catalyzed allylic alkylation. Chapter 5 discusses a major breakthrough in incorporating phosphaalkene ligands in asymmetric catalysis. Specifically, the use of chiral phosphaalkene  35 ligands in the palladium(0) catalyzed asymmetric allylic alkylation of 1,3- diphenylpropenylacetate. Chapter 6 is a summary of the result presented in this dissertation as well as a short discussion of future work.  36 CHAPTER 2 P,N-Chelate Complexes of Pd(II) and Pt(II) Based on a Phosphaalkene Motif: A Catalyst for the Overman–Claisen Rearrangement* 2.1 Introduction  Before embarking on the search for a chiral phosphaalkene ligand, a simpler achiral P,N ligand was investigated to better understand the general reactivity of P,N-chelate phosphaalkene ligands. Some previously demonstrated examples of phosphaalkene ligands are shown in Figure 2.1. Most previously known acyclic phosphaalkene-based ligands employed in catalysis utilize the sterically encumbered Mes* (2,4,6-(t-Bu)3C6H2) ligand to confer kinetic and thermodynamic stability to the P=C bond (2A77,100,138 and 2B98,111,119,122,126,133,134). Particularly relevant to the present studies are 2-pyridyl substituted phosphaalkenes 2C139 and 2D70,74 where the P=C bond is similarly flanked by the Mes* substituent. Although P(sp2),N(sp2) compounds containing acyclic phosphaalkenes have been coordinated to transition metals, to our knowledge, only ligand 2A (X = N) has been employed in catalysis (as of 2007). C C PP RR Mes**Mes NC C P *Mes P Mes* R R 2C 2D2B C PMes* R N C C PX Mes**Mes RR X = N, P 2A Figure 2.1 Ligands Containing Low-valent Phosphorus.  * A version of this chapter has been published. Julien Dugal-Tessier, Gregory, R. Dake and Derek P. Gates. P,N-Chelate Complexes of Pd(II) and Pt(II) Based on a Phosphaalkene Motif: A Catalyst for the Overman–Claisen Rearrangement. Organometallics, 2007, 26, 6481–6486.  37   The Gates group has recently employed the phospha-Peterson reaction as a general route to phosphaalkenes bearing modest degrees of steric bulk.68 The relatively mild conditions needed to affect this transformation suggested to us a route to novel chelating phosphaalkene ligands for use in transition metal catalysis. An idealized strategy for the development of phosphaalkene ligands bearing tunable donor-acceptor properties is shown in Scheme 2.1. O R X Lewis basic site C P R X Ar C P R X Ar M poor ! donor good " acceptor new reactivity in metal catalysis low valent phosphorus  Scheme 2.1 Strategy for Our P,N-Ligand.   An attractive feature of this approach is that the modular nature of the ligand synthesis allows for the facile modification of steric and electronic properties. For example, isolable phosphaalkene ligands bearing varying degrees of steric bulk (i.e. Mes and larger) may be synthesized from a variety of functional ketones using the phospha-Peterson reaction. A 2- pyridyl phosphaalkene (2.3)68 was synthesized previously in the Gates group using the base catalyzed phospha-Peterson reaction of silylphosphine 2.175 and ketone 2.2 (Scheme 2.2). + O C N KOH (cat) THF P C Mes NMes P SiMe3 SiMe3 50% 1:1 E/Z 2.32.1 2.2 Scheme 2.2 Base-Catalyzed Phospha-Peterson to Generate Pyridyl-Phosphaalkene.   38 Ketone 2.2 was commercially available and was used in the phospha-Peterson reaction after purification by sublimation. Bis(silyl)phosphine 2.1 was not commercially available and was synthesized from PCl3 by a three-step protocol (Scheme 2.3). Slow addition of MesMgBr to an excess of PCl3 gave MesPCl2,140 followed directly by LiAlH4 reduction of the crude product yielding MesPH2 after distillation. Treatment of MesPH2 with two equivalent of MeLi followed by quenching with two equivalent of Me3SiCl yielded pure 2.1 after fractional distillation (δ(31P) = −162).75 PCl3 LiAlH4 MesPH2 1)MeLi, THF –78 oC to rt 2)Me3SiCl, THF –78 oC to rt Mes P SiMe3 SiMe3 60% THF, –78 ºC to rt Et2O, –78 ºC 2.1 MesMgBr MesPCl2  Scheme 2.3 Route to Bis(trimethylsilyl)phosphine 2.1.  Two new chelating phosphaalkene-based P(sp2),N(sp2) complexes of palladium(II) and platinum(II) were synthesized; namely, MesP=C(Ph)(2-py)PtCl2 (2.4) and MesP=C(Ph)(2- py)PdCl2 (2.5) (Scheme 2.4 and 2.5 respectively). These new complexes bear the modestly bulky Mes-substituent at phosphorus compared to known P(sp2),N(sp2) complexes which often utilize the larger Mes* substituent to impart stability to the ligand. Moreover, a phosphaalkene ligated palladium(II) complex (2.5) was demonstrated to be a catalyst for the aza-Claisen rearrangement of trichloroacetimidates (Overman–Claisen rearrangement).141 2.2 Results and Discussion 2.2.1 Synthesis of Palladium(II) and Platinum(II) Complexes In an attempt to prepare platinum complex 2.4, C-pyridyl phosphaalkene 2.3 was treated with (cod)PtCl2 in CH2Cl2 at ambient temperature (Scheme 2.4). Analysis of the reaction mixture  39 by 31P NMR spectroscopy revealed that the signals assigned to E/Z-2.3 [δ = 260.1 (E), 242.1 (Z)] had been replaced by a new signal at 205.6 ppm (Figure 2.2). Importantly, the observation of 195Pt satellites (1JPtP = 4486 Hz) provided convincing evidence for the coordination of the phosphorus center to the platinum center. The Pt–P coupling constant is similar to other phosphaalkene complexes such as 2B·PtCl2 (1JPtP ≈ 4500 Hz)142,143 but is higher than the monodentate phosphaalkene in [MesP=CPh2]2PtCl2 (1JPtP = 3950 Hz).144 Moreover, the downfield 31P NMR chemical shift is consistent with retention of P=C multiple bond character in the ligand upon platinum complexation. P C N Mes (cod)PtCl2 P C N Mes Pt Cl Cl 2.42.3 CH2Cl2 (37%)  Scheme 2.4 Formation of Platinum Complex 2.4.  Figure 2.2 31P{1H} NMR (121 MHz, CDCl3) of 2.4 (δ = 206, 1JPtP = 4486 Hz).  The above 31P{1H} NMR spectroscopic evidence suggested that 2.4 had been formed from 2.3 and (cod)PtCl2, this was confirmed by an X-ray crystallographic analysis. Crystals  40 suitable for X-ray diffraction were grown by cooling a CH2Cl2/hexanes solution to –56 °C. The molecular structure is shown in Figure 2.3 and confirms that the chelate complex 2.4 had been formed successfully (the metrical parameters are discussed in Chapter 2.2.2). Despite repeated recrystallizations, according to NMR spectroscopy, there were always traces of (cod)PtCl2 present in samples of isolated 2.4.   Figure 2.3 Molecular Structure of 2.4 (50% Probability Ellipsoids). All hydrogen atoms and the solvent (½×CH2Cl2) are omitted for clarity. Selected bond length (Å) and angles (deg): Pt1-P1 = 2.1673(11), P1-C10 = 1.672(4), C10-C17 = 1.468(5), C17-N1 = 1.373(5), N1-Pt1 = 2.069(3), Pt1-Cl1 = 2.2923(11), Pt1-Cl2 = 2.3415(11), P1-C1 = 1.787(4); N1-Pt1-P1 = 81.17(10), P1-Pt1-Cl1 = 94.02(4), N1-Pt1-Cl2 = 94.80(10), Cl1-Pt1-Cl2 = 90.02(4), Pt1-N1-C17 = 120.3(3), N1-C17-C10 = 117.4(3), C17-C10-P1 = 112.3(3), C10-P1-Pt1 = 108.64(14), C10-P1-C1 = 116.15(19), Pt1-P1-C1 = 134.76(13). Reproduce with permission from Organometallics, 2007, 26, 6481–6486. © 2007 American Chemical Society.  Given the success in the preparation of 2.4, I attempted to prepare the heavier congener Pd-complex 2.5. Under analogous conditions to those described above for 2.4, phosphaalkene ligand 2.3 was treated with (cod)PdCl2 in CH2Cl2 (Scheme 2.5). Analysis of the crude reaction mixture by 31P{1H} NMR spectroscopy revealed a single resonance at 230 ppm (Figure 2.4).  41 P C N Mes (cod)PdCl2 P C N Mes Pd Cl Cl 2.52.3 CH2Cl2 53%  Scheme 2.5 Formation of Palladium Complex 2.5.   Figure 2.4 31P{1H} NMR (121 MHz, CDCl3) Spectrum of 2.5 (δ = 230).  Lower field chemical shifts were observed for pyridyl phosphaalkene complexes containing the bulkier P-Mes* moiety (i.e. 2C·PdCl2: R = H, 247 ppm; R = SiMe3, 283 ppm).139 In contrast, higher field shifts were observed for complexes 2B·PdCl2 (R = C4H4S, 149.4 ppm; R = Fc, 134.9 ppm).142,143,145 Interestingly, the 13C{1H} NMR signal assigned to the P=C carbon resonates at 174.8 ppm (1JPC = 52 Hz) for the complex 2.5 which is further upfield than that found for the free phosphaalkene 2.3 (δ = 191.3, 1JPC = 40 Hz; i.e. Δδ = 16.5). Similar upfield shifts were observed for the PdCl2 complexes of 2C·PdCl2 (R = SiMe3, Δδ = 4.6)139 and the phosphaalkene signals for complex 2B·PdCl2 (R = –(CH2)5–; Δδ = 16.0 and 14.7).146 Unlike, Pt- complex 2.4, the Pd-complex 2.5 was readily obtained in analytical purity after recrystallization.  42  Figure 2.5 Molecular Structure of 2.5 (50% Probability Ellipsoids). All hydrogen atoms and the solvent (2×CH2Cl2) are omitted for clarity. Selected bond length (Å) and angles (deg): Pd1-P1 = 2.1749(7), P1-C1 = 1.675(3), C1-C2 = 1.470(4), C2-N1 = 1.377(4), N1-Pd1 = 2.076(2), Pd1-Cl1 = 2.3412(7), Pd1-Cl2 = 2.2834(7), P1-C13 = 1.789(3); N1-Pd1-P1 = 81.43(6), P1-Pd1-Cl2 = 91.42(3), N1-Pd1-Cl1 = 95.20(6), Cl1-Pd1-Cl2 = 91.95(3), Pd1-N1- C2 = 119.96(17), N1-C2-C1 = 117.6(2), C2-C1-P1 = 112.7(2), C1-P1-Pd1 = 108.3(1), C1-P1- C13 = 116.35(13), Pd1-P1-C13 = 135.36(9). Reproduce with permission from Organometallics, 2007, 26, 6481–6486. © 2007 American Chemical Society.  2.2.2 Molecular Structures of 2.4 and 2.5 The molecular structures of 2.4 and 2.5 are shown in Figures 2.3 and 2.5 respectively, and selected metrical parameters are given in the figure captions. Details of the solution and refinement are given in Table 2.2. Interestingly, the crystal structure of the palladium(II) and platinum(II) complexes contain almost identical metrical parameters. Given that related P,N- chelate complexes of Pt(II) have not been characterized crystallographically, in this section, emphasis will be placed on comparing 2.5 with related Pd(II) compounds from the literature. In both complex 2.4 and complex 2.5, a significant shortening of the ligand’s P=C bond is observed upon metal complexation [1.672(4) Å in 2.4 and 1.675(3) Å in 2.5 vs 1.7043(16) Å in 2.3].68 In contrast, 2A (X = N), 2B and 2C showed no significant change or even a slight elongation in P=C bond length upon complexation {i.e. 1.660(11) Å in [2A·Pd(Me)(NCMe)]+ vs 1.684(2) Å in  43 2A;77 1.653(12) Å in 2B·PdCl2 vs 1.667(8) Å in 2B;146 1.674(4) Å in 2C·PdMeCl vs 1.663(3) Å in 2C}.139 The palladium-phosphorus bond length in 2.5 of 2.1749(7) Å is similar to those previously observed for phosphaalkene-palladium complexes of 2A (X = N) and 2C [av = 2.179(3) Å].77,139 However, these are slightly shorter than those observed in 2B·PdCl2 [2.267(2) Å and 2.256(2) Å].146 In addition, the N–Pd bond length in complex 2.5 of 2.076(2) Å is shorter than that for 2C·PdMeCl [2.164(4) Å]139 and that of [2A·Pd(Me)(NCMe)]+ [2.166(8) Å].77 The C–P=C angle increased significantly upon coordination of 2.3 to palladium [107.80(7)° in 2.368 vs 116.15(19)° in 2.4 and 116.35(13)° in 2.5]. Similar increases in C–P=C bond angles were observed for the palladium(II) complexes of 2A [X = N, 104.36(9)° to 113.7(5)°],77 2B [99.6(2)° to 114.1(4)°],146 and 2C [99.15(14)° to 114.26(19)°].139 The angle between the mean plane of the six carbon atoms of the Mes substituent and the PdNC2P plane in 2.5 is 69°. Not surprisingly, the complexes employing the bulkier Mes* substituent show angles between the Mes* and PdNC2P planes that are close to orthogonal {87° in [2A·Pd(Me)(NCMe)]+,77 89° in 2C·PdMeCl139}.  2.2.3 Catalytic Activity of Complex 2.5 Efforts were then undertaken to establish any catalytic activity for the phosphaalkene palladium(II) complex 2.5. A palladium(II) catalyzed process is the rearrangement of allyl trichloroacetimidates (the Overman–Claisen rearrangement).141,147,148 This process entails the transformation of an allyl alcohol into an allyl amine derivative by a 1,3-allylic transposition (Scheme 2.7).   44 R OH R O R R Cl3CCN DBU HN CCl3 [M] or ! HN O CCl3 NaOH NH2  Scheme 2.7 General Overman–Claisen Rearrangement.  The Overman–Claisen rearrangement was deemed to be a useful starting point to examine the potential catalytic reactivity of palladium phosphaalkene complexes (2.5) for two principal reasons. First, the mechanism of the palladium-catalyzed Overman–Claisen rearrangement does not involve changes in the palladium oxidation state, simplifying the overall reaction path (Figure 2.6). The accepted reaction mechanism is coordination of Pd(II) to the olefin (I) which promotes a metal catalyzed sigmatropic rearrangement (II) and then C-O bond cleavage generates olefin complex (III).148 Decomplexation liberates the Pd(II) catalyst to undergo another metal catalyzed sigmatropic rearrangement. This mechanism suggests that the metal catalyzed Overman–Claisen rearragement is a suitable reaction to investigate Lewis acidic complex [2.5] due to its strong π-accepting phosphaalkene ligand. The driving force of the Overman–Claisen is the formation of the C=O bond over the C=N bond. R OHN CCl3 [PdII] [PdII] R OHN CCl3 [PdII]- R HN O CCl3 [PdII] R OHN CCl3 R HN O CCl3 I II III  Figure 2.6 General Mechanism for the Metal Catalyzed Overman–Claisen Rearrangement.   45 Secondly, the starting materials for these processes are readily available (Scheme 2.8). Allyl alcohols can be treated with trichloroacetonitrile and DBU to form trichloroacetimidates. Linear allyl alcohols can be obtained by treatment of enones with DIBAl-H, and in turn enones can be obtained by a Horner–Wadsworth–Emmons reaction of an aldehyde.19 R O R O OEt DIBAL-H R OH Cl3CCN DBUNaH CO2Et(EtO2C)2OP R OHN CCl3 2.6a  R = Me           (86%) 2.6b  R = n-Pr         (74%) 2.6c  R = n-Hep      (75%) 2.6d  R = Ph(CH2)2 (68%) 2.6e  R = i-Pr          (75%) a  R = Me           (86%) b  R = n-Pr         (74%) c  R = n-Hep      (99%) d  R = Ph(CH2)2 (95%) e  R = i-Pr          (55%) a  R = Me           (86%) b  R = n-Pr         (74%) c  R = n-Hep      (99%) d  R = Ph(CH2)2 (68%) e  R = i-Pr          (72%) Scheme 2.8 General Method for the Generation of Linear Allylic Alcohols.  Gratifyingly, subjecting acetimidate 2.6a with 5 mol % of 2.5 in CH2Cl2 at 35 °C for 24 h led to the production of branched amide 2.7a in 91% isolated yield (Table 2.1, entry 1). Importantly, no background reaction was observed when the reaction was run in the absence of complex 2.5 (entry 2). Reactions run with substrate that was not previously purified by flash column chromatography or distillation tended to be messy, which is presumably a consequence of the sensitivity of 2.5. Purification of the starting material using either distillation (entry 1) or standard silica gel column chromatography (entry 3) gave satisfactory results. Interestingly, the reaction proceeded optimally using acetimidate starting materials possessing linear aliphatic chains (entries 4-6). Substrates containing branched aliphatic groups reacted, although the products were obtained in less satisfactory isolated yield (entry 7). We speculate that the lower yields obtained with bulky substrates may be a consequence of the bulky nature of complex 2.5. A second observation is an overall decrease in the reaction efficiency when the acetimidate substrate contained an aryl moiety. For example, compound 2.6d reacted to produce amide 2.7d in 48% isolated yield (entry 6). The addition of toluene to the reaction of 2.6a also led to a  46 similar decrease in the reaction efficiency. The inhibitory role of the aromatic additives is not clear at the present time. Future efforts to expand substrate scope will necessitate the design of improved phosphaalkene complexes. Still, these results suggest a useful starting point for mixed ligand design using a phosphaalkene as a key structural motif. Table 2.1 Results of the Aza-Claisen Rearrangement Using 2b as a Catalyst.a R1 O CCl3 HN 2.5 (x mol %) CH2Cl2, 35 oC, 24 h R1 HN CCl3 O 2.6a-e 2.7a-e entry substrate R1 2.5 (mol %) yield (%) b 1 2.6ac Me 5 91 2 2.6ad Me 0 0 3 2.6ad Me 5 84 4 2.6bd n-Pr 5 86 5 2.6cd n-Hep 5 72 6 2.6dd PhCH2CH2 5 48 7 2.6ed i-Pr 5 33 a Adapted with permission from Organometallics, 2007, 26, 6481–6486. © 2007 American Chemical Society.b Isolated yield. c Purified by distillation. d Purified by column chromatography.  2.3 Summary In closing, I have prepared two new palladium(II) and platinum(II) complexes bearing P(sp2)-N(sp2) ligands (compounds 2.4 and 2.5 respectively). The phosphaalkene-based ligand system bears a moderately bulky Mes P-substituent. Both compounds (2.4 and 2.5) were characterized spectroscopically through NMR studies and X-ray crystallographic analysis. As a proof of concept, the potential use of this ligand class in catalysis was demonstrated by showing that compound 2.5 was effective in an Overman–Claisen rearrangement. At the report of the present work, Ozawa independently published another P,N type ligand of type 2D in the rhodium catalyzed conjugate addition of enones (Chapter 1.4.5.2).127  47 2.4 Experimental Section 2.4.1 General Procedures All manipulations of air- and/or water- sensitive compounds were performed under a nitrogen atmosphere using standard Schlenk or glovebox techniques. Hexanes and CH2Cl2 were deoxygenated with nitrogen and dried by passing through a column containing activated alumina. 230–400 mesh silica was used (Silicycle). The complexes (cod)PtCl2 and (cod)PdCl2 were prepared according to literature procedures.149,150 Trichloroacetonitrile, 1,8- diazabicyclo[5.4.0]undec-7-ene (DBU), crotyl alcohol, trans-2-hexen-1-ol were used as received from Aldrich. Other starting materials were prepared according to the literature procedures, which are cited below. 1H, 31P{1H}, 13C{1H} NMR spectra were recorded at room temperature on Bruker Avance 300 or 400 MHz spectrometers. 85% H3PO4 was used as an external standard (δ=0.0 for 31P). 1H NMR spectra were referenced to residual protonated solvent and 13C NMR were referenced to the deuterated solvent. Elemental analyses were performed in the University of British Columbia Chemistry Microanalysis Facility. Mass spectra were recorded on a Kratos MS 50 instrument in EI mode (70 eV). Melting points are uncorrected.  2.4.2 Synthesis of MesPC(Ph)(2-py)PtCl2 (2.4) This procedure was performed in a glovebox. To a mixture of (cod)PtCl2 (75 mg, 0.19 mmol) and 2.3 (65 mg, 0.20 mmol) was added 1 mL of CH2Cl2. The resulting dark red solution was stirred for 15 min. Cooling of the reaction mixture to –56 °C with slow addition of 1 mL of hexanes gave yellow crystals. The mother liquor was decanted and the crystals were washed  48 with hexanes (3 × 1 mL). Recrystallization (CH2Cl2/hexanes, twice) followed by drying in vacuo for 6 h gave 41 mg (37%) of the title compound as a solid. 31P{1H} NMR (121.3 MHz, CDCl3): δ 205.6 (1JPtP = 4486 Hz); 1H NMR (300 MHz, CDCl3): δ 10.34 (dd, 3JHH = 6 Hz, 3JHH = 1 Hz, 3JPtH = 36 Hz, 1H), 7.87–7.79 (m, 1H), 7.50–7.44 (m, 1H), 7.41–7.27 (m, 4H), 7.11–7.08 (m, 2H), 6.90 (d, 3JHH = 4 Hz, 2H), 2.54 (s, 3H), 2.53 (s, 3H), 2.28 (s, 3H).  2.4.3 Synthesis of MesPC(Ph)(2-py)PdCl2 (2.5) This procedure was performed in a glovebox. To a mixture of (cod)PdCl2 (100 mg, 0.35 mmol) and 2.3 (111 mg, 0.35 mmol) was added 1 mL of CH2Cl2. The resulting dark red solution was stirred for 15 min. Cooling the reaction mixture to –56 °C with slow addition of 1 mL of hexanes gave orange crystals. The mother liquor was decanted and the crystals were washed with hexanes (3 × 3 mL) and dried in vacuo at 100 °C for 6 h to give 91 mg (53%) of the title compound as orange crystals. 31P{1H} NMR (121.3 MHz, CDCl3): δ 230.4 (s); 1H NMR (300 MHz, CDCl3): δ 10.03 (d, 3JHH = 6 Hz, 1H), 7.86 (dd, 3JHH = 4 Hz, 3JHH = 2 Hz, 1H), 7.48–7.44 (m, 1H), 7.39–7.24 (m, 4H), 7.07 (d, 3JHH = 8 Hz, 2H), 6.85 (d, 3JHH = 4 Hz, 2H), 2.50 (s, 3H), 2.50 (s, 3H), 2.25 (s, 3H); 13C{1H} NMR (75 MHz, CD2Cl2): δ 174.8 (d, JPC = 52 Hz), 163.0, 159.7 (d, JPC = 14 Hz), 155.2 (d, JPC = 5 Hz), 145.8 (d, JPC = 3 Hz), 144.0 (d, JPC = 5 Hz), 140.8 (d, JPC = 5 Hz), 134.4 (d, JPC = 13 Hz) 130.3, 129.6, 129.3 (d, JPC = 10 Hz), 128.4 (d, JPC = 14 Hz), 125.9 (d, JPC = 9 Hz), 124.0 (d, JPC = 25 Hz), 120.2 (d, JPC = 38 Hz), 23.5, 23.4, 21.9; anal. calcd for C21H20NPdCl2: C, 50.99; H, 4.08; N, 2.83; Found: C, 51.12; H, 4.21; N, 2.80.   49 2.4.4 Trichloroacetimidate Formation (General Procedure) To a solution of allylic alcohol (1 equiv) in CH2Cl2 (0.1 M) at 0 °C was added trichloroacetonitrile (1.5 equiv) and then DBU (0.2 equiv) dropwise. The reaction mixture was stirred at 0 °C for 1 h. The reaction was quenched by the addition of a saturated aqueous solution of sodium bicarbonate. The organic and aqueous fractions were separated, and the aqueous phase was extracted twice with CH2Cl2. The combined organic extracts were dried (sodium sulfate), and concentrated by rotary evaporation in vacuo. Further purification of the crude material using flash column chromatography on silica gel was typically necessary.  2.4.5 Synthesis of 1-( l-Imino-2,2,2-trichloroethoxy)-2(E)–butene (2.6a) Crotyl alcohol (1.10 g, 13.9 mmol) was processed as outlined in the general procedure. Purification using flash column chromatography (hexanes/EtOAc, 95:5) gave 2.85 g (86%) of a colorless oil. The spectroscopic data for the title compound was identical to literature.151  2.4.6 Synthesis of 1-(1-Imino-2,2,2-trichloroethoxy)-2(E)-hexene (2.6b) (E)-2-Hexen-1-ol (1.14 g, 11.3 mmol) was processed as outlined in the general procedure. Purification using flash column chromatography (hexanes/EtOAc, 95:5) gave 2.05 g (74%) of a colorless oil. The spectroscopic data for the title compound was identical to literature.152   50 2.4.7 Synthesis of 1-(1-Imino-2,2,2-trichloroethoxy)-2(E)–decene (2.6c) (E)-2-Decen-1-ol153 (2.67 g, 17.1 mmol) was processed as outlined in the general procedure. Purification using flash column chromatography (hexanes/EtOAc, 95:5) gave 3.84 g (75%) of a colorless oil. 1H NMR (300 MHz, CDCl3): δ 8.32–8.20 (br s, 1H), 5.87 (dt, 3JHH = 15 Hz, 3JHH = 7 Hz, 1H), 5.66 (dtt, 3JHH = 15 Hz, 3JHH = 6 Hz, 4JHH = 1 Hz, 1H), 4.72 (dd, 3JHH = 6 Hz, 4JHH = 1 Hz, 2H), 2.05 (q, 3JHH = 7 Hz, 2H), 1.40–1.23 (m, 10H), 0.86 (t, 3JHH = 7 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 162.5, 137.0, 122.9, 91.5, 69.9, 32.2, 31.8, 29.1, 29.0, 28.8, 22.6, 14.0; IR (neat, NaCl): 3347, 1663, 1290 cm-1; LRMS (EI): m/z [%] 301 [33, M+] 299 [36, M+], 266 [48, M+ – Cl], 264 [71, M+ – Cl], 216 [85, M+ – C6H13], 214 [84, M+ – C6H13], 202 [96, M+ – C7H15], 200 [100, M+ – C7H15].  2.4.8 Synthesis of 1-(1-Imino-2,2,2-trichloroethoxy)-2(E)-5-phenyl-pentene (2.6d) (E)-5-Phenyl-2-penten-1-ol154 (1.43 g, 8.8 mmol) was processed as outlined in the general procedure. Purification using flash column chromatography (hexanes/EtOAc, 95:5) gave 1.85 g (68%) of a colorless oil. The spectroscopic data for the title compound was identical to literature.155   51 2.4.9 Synthesis of 1-(1-Imino-2,2,2-trichloroethoxy)-2(E)-4-methyl-pentene (2.6e) (E)-4-Methyl-2-penten-1-ol156 (0.36 g, 3.6 mmol) was processed as outlined in the general procedure. Purification using flash column chromatography (hexanes/EtOAc, 95:5) gave 0.66 g (75%) of a colorless oil. 1H NMR (400 MHz, CDCl3): δ 8.35–8.20 (br s, 1H), 5.84 (dd, 3JHH = 16 Hz, 3JHH = 6 Hz, 1H), 5.63 (dt, 3JHH = 16 Hz, 3JHH = 6 Hz, 1H), 4.75 (d, 3JHH = 6 Hz, 2H), 2.35 (sept, 3JHH = 7 Hz, 1H), 1.02 (d, 3JHH = 7 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 162.8, 143.8, 120.3, 91.7, 70.3, 31.0, 22.1; IR (neat, NaCl); 3344, 1663, 1290 cm-1; LRMS (EI): m/z [%] 244 [36, M+ – H], 242 [37, M+ – H].  2.4.10 Palladium(II) Catalyzed Overman–Claisen Rearrangement (General Procedure) This procedure was performed in a glovebox. To a mixture of complex 2.5 (0.05 equiv) and trichloroacetimidate (1 equiv) was added 2 mL of CH2Cl2. The reaction mixture was stirred for 24 h. The reaction mixture was removed from inert atmosphere and chromatographed directly on silica gel to afford the trichloroacetamide product.  2.4.11 Synthesis of 2,2,2-trichloro-N-(1-methylallyl)acetamide (2.7a) 2.6a (96 mg, 0.44 mmol) and 2.5 (10 mg, 0.02 mmol) was processed as outlined in the general procedure. Purification using flash column chromatography (hexanes/EtOAc, 95:5) gave  52 87 mg (91%) of a white solid, mp 37–39 °C (lit. 37–38 °C).155 The spectral data for the title compound matched the literature data.155  2.4.12 Synthesis of 2,2,2-trichloro-N-(1-propylallyl)acetamide (2.7b) 2.6b (98 mg, 0.40 mmol) and 2.5 (10 mg, 0.02 mmol) was processed as outlined in the general procedure. Purification using flash column chromatography (hexanes/EtOAc, 95:5) gave 84 mg (86%) of a colorless oil. The spectral data for the title compound matched the literature data.155  2.4.13 Synthesis of 2,2,2-trichloro-N-(1-heptylallyl)acetamide (2.7c) 2.6c (143 mg, 0.47 mmol) and 2.5 (12 mg, 0.024 mmol) was processed as outlined in the general procedure. Purification using flash column chromatography (hexanes/EtOAc, 99:1) gave 103 mg (72%) of a colorless oil. 1H NMR (300 MHz, CDCl3): δ 6.55–6.45 (br s, 1H), 5.79 (ddd, 3JHH = 17 Hz, 3JHH = 11 Hz, 3JHH = 6 Hz, 1H), 5.28–5.22 (m, 2H), 4.45–4.35 (m, 1H), 1.69–1.56 (m, 2H), 1.40–1.20 (m, 10H), 0.88 (t, 3JHH = 7 Hz, 3H); 13C{1H} NMR(75 MHz, CDCl3): δ 161.1, 136.7, 116.0, 92.9, 53.5, 34.5, 31.7, 29.2, 29.1, 25.5, 22.6, 14.0; IR (Neat, NaCl): 3423, 1694, 1519 cm-1; LRMS (EI): m/z [%] 301 [8, M+], 299 [9, M+], 266 [15, M+ – Cl], 264 [23, M+ – Cl], 202 [70, M+ – C7H15], 200 [100, M+ – C7H15]. anal. calcd For C12H20Cl3NO: C, 47.94; H, 6.71; N, 4.66; Found: C, 47.63; H, 6.50; N, 5.05.   53 2.4.14 Synthesis of 2,2,2-trichloro-N-(1-(2-phenylethyl)-allyl)acetamide (2.7d) 2.6d (160 mg, 0.52 mmol) and 2.5 (13 mg, 0.027 mmol) was processed as outlined in the general procedure. Purification using flash column chromatography (hexanes/EtOAc, 98:2) gave 76 mg (48%) of the title compounds as a colorless oil. The spectral data for the title compound matched the literature data.157  2.4.15 Synthesis of 2,2,2-trichloro-N-(1-isopropylallyl)acetamide (2.7e) 2.6e (196 mg, 0.80 mmol) and 2.5 (20 mg, 0.04 mmol) was processed as outlined in the general procedure. Purification using column chromatography (hexanes/EtOAc, 98:2) gave 65 mg (33%) of the title compound as a white solid, mp 42–43 °C. 1H NMR (400 MHz, CDCl3): δ 6.73–6.51 (br s, 1H), 5.80 (ddd, 3JHH = 17 Hz, 3JHH = 10 Hz, 3JHH = 6 Hz, 1H), 5.25–5.19 (m, 2H), 4.31–4.28 (m, 1H), 1.93 (sept, 3JHH = 7 Hz, 1H), 0.97 (d, 3JHH = 7 Hz, 3H), 0.95 (d, 3JHH = 7 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 161.4, 135.3, 116.9, 93.1, 58.9, 32.2, 18.9, 18.0; IR (neat, NaCl) 3301, 1690, 1530 cm-1; LRMS (EI): m/z [%] 245 [16, M+], 243 [17, M+], 202 [97, M+ – C3H7], 200 [100, M+ – C3H7].  2.4.16 X-Ray Crystallography of 2.4 and 2.5 All single crystals were immersed in oil and mounted on a glass fiber. Data were collected on a Rigaku/ADSC CCD diffractometer (2.4) or a Bruker X8 APEX diffractometer (2.5) with graphite-monochromated Mo Kα radiation. All structures were solved by direct methods and subsequent Fourier difference techniques. All non-hydrogen atoms were refined anisotropically with hydrogen atoms being included in calculated positions but not refined. All  54 data sets were corrected for absorption effects (TwinSolve for 2.4, SADABS for 2.5), Lorentz and polarization effects. All calculations on crystal 2.4 were performed using SHELXL-97,158 whereas all refinement of 2.5 were performed using SHELXTL159 crystallographic software package from Bruker-AXS. Compound 2.4 crystallized with one disordered, half molecule of dichloromethane residing on an inversion center in the asymmetric unit. Compound 2.5 crystallized with two disordered molecules of dichloromethane in the asymmetric unit. Additional crystal data and details of the data collection and structure refinement are given in Table 2.2.  55 Table 2.2 X-ray Crystallographic Data for 2.4 and 2.5.a  2.4 2.5 formula C21H20NPPtCl2·½CH2Cl2 C21H20NPPdCl4·2CH2Cl2 fw 625.80 664.50 cryst syst triclinic triclinic space group P ! 1  P ! 1 color yellow orange a (Å) 9.8721(7) 9.8650(3) b (Å) 10.2072(7) 11.7091(4) c (Å) 12.0467(8) 12.5723(5) α (deg) 105.168(6) 86.292(1) β (deg) 108.919(6) 88.685(1) γ (deg) 95.834(6) 69.904(1) V (Å3) 1085(1) 1360.96(8) T (K) 173 173 Z 2 2 µ(Mo Kα) (cm-1) 69.17 13.43 cryst size (mm3) 0.35 × 0.20 × 0.12 0.07 × 0.07 × 0.12 calcd density (Mg m-3) 1.916 1.622 2θ(max) (deg) 55.2 55.8 no. of reflns 11319 22108 no. of unique data 4068 6431 R(int) 0.025 0.031 refln/param ratio 15.41 18.48 R1b 0.026; I > 2σ(I) 0.037; I > 2σ(I) wR2 (all data)c 0.065 0.097 GOF 1.09 1.03 a Adapted with permission from Organometallics, 2007, 26, 6481–6486. © 2007 American Chemical Society. b R1 = Σ||Fo|-|Fc||/Σ|Fo|. c wR2(F2[all data]) = {Σ[w(Fo2 – Fc2)2]/Σ[w(Fo2)2]}1/2  56 CHAPTER 3 Enantiomerically Pure Phosphaalkenes: Synthesis and Polymerization* 3.1 Introduction In Chapter 2, I described a novel P,N-chelate phosphaalkene ligand system bearing the moderately sized P-Mes substituent, which supported catalysis. As mentioned in the introductory chapter, phosphaalkenes are strong π-acceptor and weak σ-donors. Classical π-accepting ligands, such as CO, cannot be reconstituted into “chiral versions” for asymmetric catalysis. Consequently, the introductions of low coordinate, π-accepting phosphorus atoms within a readily available framework may fill an important gap in ligand design. At the start of this project, the only enantiomerically pure P(sp2)-based ligands used in asymmetric catalysis were of the cyclic type such as phosphinines and phosphaferrocenes. It is important at this point to discuss a previously reported example in the phosphaalkene literature (Scheme 3.1).160 Mathey and coworkers published a tungsten carbonyl phosphaalkene complex bearing a L-menthol derived P-substituent (3.2). The metal complex was further elaborated diastereoselectively to enantiomerically enriched phosphines (3.3) containing a stereogenic center at the phosphorus atom. The free phosphaalkene as well as catalytic activity with the tungsten complex (3.2) were not reported. The presence of tungsten was required for the  * Versions of sections of this chapter have been published or will be published. Julien Dugal- Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. Julien Dugal-Tessier, Paul-Steffen Kuhn, Gregory. R. Dake and Derek P. Gates. Synthesis of Functional Phosphines with Ortho-Substituted Aryl Groups: 2-RC6H4PH2 and 2- RC6H4P(SiMe3)2 (R = i-Pr or t-Bu). Heteroatom Chemistry, 2010, 21, 355-360. Julien Dugal- Tessier, Emmanuel B. Castillo-Contreras, Eamonn D. Conrad, Gregory R. Dake and Derek P. Gates, to be submitted.  57 hydrogenation of 3.2 as well as to stabilize the phospha-Horner–Wadsworth–Emmons precursor 3.1. This work, however, developed an access to novel P-chiral phosphine ligands and not to a phosphaalkene ligand for catalysis. P C CHMe2 H W(CO)5 P W(CO)5 H CH2CHMe2 H H2, RhL2 + 3.1 3.2 H P P O OEt OEt W(CO)5 1) n-BuLi 2) Me2CHCHO 3.3 Scheme 3.1 Complex of a L-Menthol Substituted Phosphaalkene.  We were inspired by motifs developed for trivalent phosphorus ligands (see, Figure 1.1). The majority of the successful ligands are bidentate and chelate metal centers to form between 5 to 7 membered rings. The successes of the chiral inducing motifs in the proligands indicated in Figure 1.1 were attractive as chiral inducing moieties for a phosphaalkene ligand. The experience gained in Chapter 2 in handling a P(sp2),N(sp2) phosphaalkene had an influence in choosing to start with a P(sp2),N(sp2) enantiomerically pure phosphaalkene proligand. This chapter discusses the initial attempts and the work leading to the synthesis of enantiomerically pure phosphaalkene proligands. Furthermore, the properties and characterization data are discussed in more detail for these novel phosphaalkene proligands.  3.2 Results and Discussion 3.2.1 General Synthetic Strategy Before embarking on the synthesis of enantiomerically pure phosphaalkenes, three features were considered when designing an approach to these species: modularity, accessibility,  58 and tunability. The following are the specific elements that were selected to accomplish the goals of our synthetic strategy. Amino acids were selected as a modular source of enantiomerically pure material because they are cheap, commercially available and versatile. Oxazolines derived from amino acids were chosen as a chiral inducing moiety since they are commonly incorporated in a variety of different chiral ligand motifs, such as phosphinooxazolines (PHOX) and bisoxazolines (box). Another advantage of using amino acid-based oxazolines is the ease of their synthesis in large quantities without recourse to flash column chromatography. The selection of a modular functional group that could be converted to a phosphaalkene was also an important consideration. Aryl ketones were selected as phosphaalkene precursors because they are readily available and the electronic properties of the α-aromatic group can be tuned. In addition, a variety of convenient methods for the phospha-olefination of aryl ketones and aldehydes have been developed such as the phospha-Peterson,67,68,75 the phospha-Wittig55-62 and the transfer of a metalphosphinidene.63-66 We elected to use the phospha-Peterson route due to its ability to tolerate substituents of moderate (Mes) and large (Mes*) size.68 Our synthetic approach to enantiomerically pure phosphaalkenes is summarized in Scheme 3.2. P C N OR2 Ar R H2N HO R P(SiMe3)2 ORR2 Ar O "chiral pool" starting material"linker" O C N OR2 R phospha-Peterson  Scheme 3.2 General Synthetic Strategy to Access Phosphaalkenes.   59 3.2.2 Preliminary Attempt at the Synthesis of Chiral Phosphaalkene  At first glance, ketone 3.5 appears to be a suitable phosphaalkene precursor since it contains an oxazoline core and no enolizable protons (Scheme 3.3). A route to ketone 3.5 was previously developed and this allowed for rapid investigation of its potential as a phosphaalkene precursor.161 Ketone 3.5 was obtained according to a modified literature procedure by a peptide coupling of phenyl glyoxylic acid (3.4) followed by two-step cyclodehydration.161 With ketone 3.5 in hand, the pivotal phospha-Peterson reaction was attempted. Treatment of 3.5 with MesP(SiMe3)Li and subsequent analysis of the reaction mixture by 31P{1H} NMR spectroscopy did not reveal any resonances attributable to a phosphaalkene [δ(31P) = >200], but instead revealed the presence of interesting and unexpected products. Further analysis of the reaction mixture by 31P NMR spectroscopy permitted the assignment of the major resonances [ca. 70%] to two compounds containing a P–P single bond [δ = 32 (d, 1JPP = 202 Hz), 4 (d, 1JPP = 202 Hz) and δ = 32 (d, 1JPP = 196 Hz), 0 (d, 1JPP = 196 Hz)]. X-ray quality crystals of the major reaction mixture components were obtained from a saturated hexanes solution. The solid state molecular structure secured the arrangement of the two diastereomers 3.6a and 3.6b present in the reaction mixture (Figure 3.1). We speculate that the formation of 3.6a and 3.6b instead of the desired phosphaalkene is a consequence of π-conjugation between the ketone and the oxazoline ring. Modification of the framework was necessary in order to minimize the formation of rings.  60 Ph O 1) MesP(SiMe3)Li –78 ºC, THF 2) Me3SiClO N Ph O OH O 1) L-valinol, DCC, HOBt, DMAP, CH2Cl2 2)SOCl2, CH2Cl2, then Na2CO3, DMF 3.6a/3b Ph N PP O Mes Mes Ph N PP O Mes Mes 3.4 3.5 3.6b3.6a Scheme 3.3 Initial Investigation Towards Enantiomerically Pure Phosphaalkenes.   Figure 3.1 Molecular Structure of 3.6a (50% Probability Ellipsoids). All hydrogen atoms (except H19) and 3.6b were omitted for clarity. Selected bond lengths (Å) and angles (deg): C1–P1 = 1.834, C10–C11 = 1.447(5), C10–C17 = 1.343(5), C10–P1 = 1.810(4), C17–O1 = 1.341(4), C17–N1 = 1.354(5), C23–P2 = 1.824(4), N1–P2 = 1.727(3), P1– P2 = 2.213(3); C17–C10–P1 = 113.0(3), C11–C10–P1 = 120.6(3), O1–C17–C10 = 126.3(4), O1–C17–N1 = 110.1(3), C10–C17–N1 = 123.6(4), C10–P1–C1 = 108.0(2), C10–P1–P2 = 93.2(1), N1–P2–C23 = 104.5(2), N1–P2–P1 = 92.0(1), C23–P2–P1 = 105.0(1).   61 3.2.3 Isolation of an Enantiomerically Pure Phosphaalkene We hypothesized that the addition of a gem-dimethyl methylene linker would inhibit ring formation by breaking π-conjugation between the ketone and the oxazoline ring. Ketone 3.8 became the new phosphaalkene precursor and a practical route to its synthesis was developed (Scheme 3.4). The known oxazoline 3.7 was prepared in one step from L-valinol using a modified literature procedure.162,163 My attempts to deprotonate 3.7 using LDA or n-BuLi were unsuccessful. Fortunately, treatment of 3.7 with s-BuLi and TMEDA for one hour at −78 ºC formed the desired carbanion.164 Claisen-type condensation of this anion with ethyl benzoate formed ketone 3.8 in 49% isolated yield. Importantly, these synthetic steps were performed on 20 g scale without the need for flash chromatography. Ph O O N H2N OH xylenes, Dean–Stark N O 1) s-BuLi, TMEDA, THF, –78 ºC 2) PhCO2Et THF, –78 ºC to rt L-valinol 3.7 3.8 i-PrCO2H  Scheme 3.4 Synthesis of Enantiomerically Pure Phosphaalkene Precursor.  Having secured a supply of ketone 3.8, its phospha-olefination was attempted. A cold (−78 ºC) THF solution of MesP(SiMe3)Li was treated with a solution of 3.8 in THF (Scheme 3.5). The reaction mixture was warmed slowly to room temperature (1 h) whereupon an aliquot was removed for analysis by 31P{1H} NMR spectroscopy. Importantly, the signal assigned to MesP(Li)SiMe3 [δ(31P) = −187] was replaced by a new singlet resonance at 244 ppm which is consistent with that expected for a phosphaalkene [cf. MesP=CPh2: δ(31P) = 233]. The presence of only a single signal suggests that only one isomer is formed. The product was recrystallized from n-pentane to afford colorless crystals of E-3.9a (52% yield), which were characterized  The expected S configuration and its enantiomeric purity was confirmed by the Flack  Paragraph has been removed for copyright reasons. The paragraph described the synthesis of compound 3.8 shown in Scheme 3.4. The information can be found in the 4th paragraph of the original source. Julien Dugal-Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.  Paragraph has been removed for copyright reasons. The paragraph described the synthesis of compound 3.9a shown in Scheme 3.5. The information can be found in the 5th p ragraph of the original source. Julien Dugal-Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand I corporating an A yclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.  62 parameter [0.13(9)] being close to zero. In addition, phosphaalkene 3.9a and all the compounds leading to it were optically active. Together, these observations suggest that the optical purity of L-valine was not lost during the synthetic sequence. The solid state molecular structure also confirmed that the P=C bond geometry observed in solution was the E-isomer.  Ph O O N Ph C P O N 1) MesP(SiMe3)Li –78 ºC, THF 2) Me3SiCl Mes 3.8 3.9a Scheme 3.5 Synthesis of an Enantiomerically Pure Phosphaalkene.  Figure 3.2 shows an ORTEP representation of the solid state molecular structure of 3.9a. Selected metrical parameters are included in the figure caption. The P=C bond length in 3.9a [1.679(2) Å] is in the normal range found in C-substituted phosphaalkenes (1.61–1.71 Å).18 The P–Mes bond in 3.9a [P(1)–C(1) = 1.826(2) Å] is also similar to analogous phosphaalkenes (ca. 1.83 Å).68 Interestingly, the Mes–P=C angle in 3.9a [C(1)–P(1)–C(10) = 105.3(1)º] is more acute than the ones found in related structures (ca. 108º).68 Presumably this is a consequence of increased steric repulsion between the methyl groups of the trans-configured CMe2-linker and the Mes substituent at phosphorus. Of particular interest is the fact that the dihedral angle between the best plane of the C-Ph substituent and the plane of the P=C bond in 3.9a (80.4º) is greater than in other Mes substituted phosphaalkenes (ca. 49º).68 Similarly but less dramatic, the dihedral angle between the best plane of the Mes substituent and the P=C bond (78.6º) is also greater than other related P-Mes phosphaalkenes (ca. 71º).68 In contrast to related phosphaalkenes, these large dihedral angles suggest that there is little to no π-conjugation in 3.9a. Presumably, the presence of the bulky CMe2–Ox group is responsible for this increased  63 twisting. To confirm this speculation it would be nice to compare to MesP=CPh(t-Bu), but this compound has not been reported.  Figure 3.2 Molecular Structure of 3.9a (50% Probability Ellipsoids). All hydrogen was omitted for clarity. Selected bond lengths (Å) and angles (deg): C1–P1 = 1.826(2), C10–P1 = 1.679(2), C10–C11 = 1.485(3), C10–C17 = 1.529(3), C17–C20 = 1.511(3), C20–O1 = 1.356(3), C20–N1 = 1.248(3); C10–P1–C1 = 105.3(1), C11–C10–P1 = 124.1(2), C17–C10–P1 = 119.2(2), C20–C17–C10 = 108.9(2), N1–C20–O1 = 118.6(2), N1–C20–C17 = 113.7(2); C25–C23–C24 = 110.5(2). Reproduced with permission from Angew. Chem. Int. Ed., 2008, 47, 8064-8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.  Surprisingly, phosphaalkene 3.9a, bearing the moderately sized Mes substituent, is stable to air and moisture. Crystals of 3.9a were left open to air for two months without any sign of decomposition as analyzed by 31P{1H} NMR spectroscopy. Moreover, the 31P{1H} NMR spectrum of 3.9a showed no change when a toluene solution was refluxed (12 h) or when a CH2Cl2 or THF solutions were saturated with water or oxygen (ca. 1 h). These properties suggest that phosphaalkene 3.9a can be manipulated without the need for special precautions, an advantageous property for its use in catalysis. However, phosphaalkene 3.9a reacts with aqueous acid (HCl) or in the presence of oxidizing agents such as m-CPBA or H2O2.   Figure 3.2 has been removed for copyright reasons. The figure depicted the solid state molecular structure of 3.9a with selected metrical parameters and is found as Figure 1 in the original source. Julien Dugal-Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.  64  3.3.4 Modification of the P-Aryl Group, Carbon Backbone and Electronic Properties of the PhAk–Ox Proligand  Modification of the backbone was important to test the versatility of the synthetic route and to tune the properties of the ligand to improve its catalytic performance. Three distinct parts of the phosphaalkene–oxazoline motif were modified: the P-aryl substituent, the C-aryl substituent, and the structure of the carbon backbone. Modification of the ligand properties will allow for the optimization of yields and enantioselectivities.  3.3.4.1 Modification of the Steric Properties of the P-Substituent The P-substituent is located next to the metal binding site and, consequently, the nature of its steric properties is expected to significantly affect reactivity. Introducing different P-aryl groups was accomplished by adding different phosphides to ketone 3.8. Some catalytic reactions require conditions that might lead to unfavorable reactions of the phosphaalkene ligand bearing smaller P-substituents. Phosphaalkene 3.9b with the larger 2,4,6-(i-Pr)3C6H2 group was synthesized in 93% yield by treating ketone 3.8 in an analogous fashion with 2,4,6-(i- Pr)3C6H2P(SiMe3)Li. Isolable phosphaalkenes traditionally contain substituents in both the 2- and 6- positions of the P-aryl group to impart steric protection above and below the P=C bond plane. Substitution at only one ortho-aryl position differentiates both faces and could be attractive for asymmetric catalytic applications. Phosphaalkene–oxazolines with a P-aryl group substituted only at the 2- position would have a steric profile that roughly resembles a box ligand.165 Isolable  65 phosphaalkenes with 2-substituted P-aryl groups are very rare, with examples being limited to 2- [Me3SiOC(O)]C6H4P=CR(OSiMe3),166 and a Ru complex of 3,3-diphenyl3H-phosphindole.167 A previous attempt at generating (2-MeC6H4)P=CPh2 reportedly led to “polymeric” material although this material was not characterized.17 Although the stability of a mono-ortho-aryl phosphaalkene was uncertain and its phosphorus phosphaalkene precursor was unknown we moved ahead and attempted to synthesize 2-i-PrC6H4P(SiMe3)2 and 2-t-BuC6H4P(SiMe3)2, and their corresponding phosphaalkenes. The synthesis starts with aryl bromides 3.10 and 3.11, prepared from the corresponding commercially available aniline derivatives using a Sandmeyer reaction,168 Scheme 3.6. The addition of magnesium metal to the aryl bromide (3.10 or 3.11) in THF generates the respective Grignard reagents which are then treated with ClP(NEt2)2.169 The use of diethylamino-protected chlorophosphine instead of PCl3 ensures that only a single aryl-substitution occurs at phosphorus. Analysis of the product by 31P{1H} NMR spectroscopy confirms that only a single product is formed and the chemical shift is consistent with its formulation as 2-RC6H4P(NEt2)2 (R = i-Pr: δ = 94; R = t-Bu: δ = 93). Although it is possible to isolate the bis(aminophosphine)s, we found it more convenient to simply treat the crude product with anhydrous hydrogen chloride in CH2Cl2 to remove the diethylamino protecting groups. The dichlorides 3.12 and 3.13 are obtained in satisfactory overall yields after distillation (69% and 78% respectively). The products were analyzed by 31P{1H} NMR spectroscopy (3.12: δ = 164, 3.13: δ = 166). These chemical shifts are similar to related dichloroarylphosphines such as MesPCl2 (δ = 167).170 Reduction of the dichlorides 3.12 and 3.13 using LiAlH4 affords primary phosphines 3.14 and 3.15 in good isolated yield (70%, 82%, respectively). Although phosphine 3.14 has previously been mentioned, its synthesis and characterization were not reported.171 Analysis of the products using 31P NMR spectroscopy revealed triplet resonances that are characteristic of primary  66 phosphines [3.14: δ = −127 (t, 1JPH = 203 Hz), 3.15: δ = −107 ppm (t, 1JPH = 202 Hz)]. The final step in the preparation of bis(trimethylsilyl)phosphines 3.16 and 3.17 involves treating 3.14 or 3.15 with MeLi (2 equiv) followed by silylation using Me3SiCl. The desired bis(trimethylsilyl)phosphines were isolated in reasonable yield after distillation (3.16: 48%, 3.17: 72%). R NH2 R PCl2 3.12 R = i-Pr  (69%) 3.13 R = t-Bu (78%) 1) Mg, THF 2) ClP(NEt2)2 3) HCl(g), CH2Cl2 R PH2 3.16 R = i-Pr  (48%) 3.17 R = t-Bu (72%) LiAlH4 (0.75 equiv) Et2O, –78 ºC to rt R P(SiMe3)2 3.14 R = i-Pr  (70%) 3.15 R = t-Bu (82%) 1)MeLi, THF, –78 ºC to rt 2)Me3SiCl, THF, –78 ºC to rt R Br 3.10 R = i-Pr (46%) 3.11 R = t-Bu (30%) 1) 48% HBr, NaNO2 2) 48% HBr, CuBr  Scheme 3.6 Synthesis of 2-RC6H4P(SiMe3)2 (R = i-Pr; R = t-Bu).  Remarkably, the treatment of ketone 3.8 with in situ generated 2-i-PrC6H4P(SiMe3)Li afforded phosphaalkene 3.9c (85%) after distillation (Scheme 3.7). The same procedure was repeated with in situ generated 2-t-BuC6H4P(SiMe3)Li yielding 3.9d (83%). These examples are a testament to the power and generality of the phospha-Peterson route. Ph O O N Ph C P O N THF, –78 ºC then Me3SiCl Mes 3.8 3.9a: Ar = Mes 3.9b: Ar = 2,4,6-(i-Pr)3C6H2 3.9c: Ar = 2-(i-Pr)C6H4 3.9d: Ar = 2-(t-Bu)C6H4 + ArP(SiMe3)Li  Scheme 3.7 Modification of the P-Substituent.   67 3.3.4.2 Modification of the C-Substituent to Tune Bite Angle and the Electronic Properties Phosphaalkene–oxazolines are P,N-bidentate ligands and, consequently, modification of the bite angle, the relative donor-acceptor properties and the steric environment can affect reactivity. In order to compare the effect of these modifications only phosphaalkenes with the Mes substituent at phosphorus were investigated. In order to vary these parameters, several new ketones were synthesized. The bite angle of a ligand (i.e. box type) can be tuned by modifying the nature of the linker group.172-175 Along those lines we were interested in modifying the gem-dimethyl linker in PhAk–Ox ligands with carbocycles (R1) (Scheme 3.8). A cyclopentyl linker was introduced using an analogous synthetic sequence to that developed for the gem-dimethyl linker (Scheme 3.8). Condensation of L-valinol with cyclopentyl carboxylic acid generated oxazoline 3.18, and subsequent Claisen-type condensation with ethyl benzoate afforded ketone 3.20 (70%). Treatment of a THF solution of MesP(SiMe3)Li with a THF solution of ketone 3.20 gave cyclopentyl phosphaalkene 3.22a in 50% yield (Scheme 3.8). Despite our efforts to grow crystals, thus far we have been unable to obtain a solid state molecular structure of compound 3.22a to assess the effect of the cyclopentyl group on the free ligand and its bite angle. The electronic properties of the P=C bond can also be modified by the electronic properties of the C-aryl group (R2). Different C-aryl groups can be introduced by selecting the appropriate electrophile in the Claisen-type condensation (Scheme 3.8). Using this strategy, ketone 3.19 bearing the electron donating C-aryl (R2 = MeOC6H4) was obtained (72%) from the condensation of oxazoline 3.8 with methyl 4-methoxybenzoate (ii, Scheme 3.8). Ketone 3.21 bearing the electron withdrawing 3,5-bis(trifluoromethyl)phenyl group was synthesized analogously using a Weinreb amide as the electrophile (iii, Scheme 3.8). Phospha-Peterson  68 reaction of ketones 3.19 and 3.21 proceeded smoothly to generate phosphaalkenes 3.23a and 3.24a in 50% and 60% yields respectively. In summary, electron donating and electron withdrawing C-aryl groups can both be introduced in a convergent manner. Electrophiles (i)  PhCO2Et (ii) 4-(MeO)C6H4CO2Me (iii) 3,5-(CF3)2C6H3CON(OMe)Me R2 O R1 R1 O NN O R1 R1 1) s-BuLi, TMEDA, THF, –78 ºC 2) Electrophile THF, –78 ºC to rt 3.8: R1 = Me 3.18: R1 = (CH2)4 3.19: R1 = Me, R2 =  4-(MeO)C6H4 3.20: R1 = (CH2)4, R 2 = Ph 3.21: R1 = (CH2)4, R 2 = 3,5-(CF3)2C6H3 R2 C P R1 R1 O N 1) MesP(SiMe3)Li –78 ºC, THF 2) Me3SiCl, –78 ºC, THF Mes 3.22a: R1 = (CH2)4, R 2 = Ph 3.23a: R1 = Me, R2 = 4-(MeO)C6H4 3.24a: R1 = (CH2)4, R 2 = 3,5-(CF3)2C6H3 Scheme 3.8 Modification of the of PhAk–Ox Proligand’s Carbon Framework.  The synthetic strategy outlined in Scheme 3.2 is a practical method at generating a variety of different phosphaalkene–oxazolines (Figure 3.3). These phosphaalkenes were synthesized on the gram scale with varying carbon backbones and P-aryl substituents. In the process of investigating the synthetic strategy a small sample set of PhAk–Ox proligands was obtained. This set will allow for future testing of different structural parameters on the catalytic activity. This in turn will lead to the synthesis of new and improved PhAk–Ox proligands.   69 C O NP C O NP i-Pr i-Pr i-Pr C O NP i-Pr C O NP t-Bu C O NP C O NP MeO C O NP F3C F3C 3.9a 3.9b 3.9c 3.9d 3.22a 3.23a 3.24a Figure 3.3 Variety of Phosphaalkene–Oxazoline Proligands.  3.3.5 NMR Parameters of Phosphaalkene–Oxazolines  The synthesis of a small set of phosphaalkene–oxazolines (PhAk–Ox) (Figure 3.3) permits the qualitative analysis of the effect of substitution on the P=C bond. The NMR spectroscopic data for new chiral phosphaalkenes are presented in Table 3.1. The 31P{1H} NMR spectrum of prototypical phosphaalkene 3.9a [δ(31P) = 244] has a downfield chemical shift compared to the spectra of other related C-substituted phosphaalkenes such as MesP=CPh2 [δ(31P) = 233]17 and MesP=CH(t-Bu) [δ(31P) = 224].67 Similarly, the 13C{1H} NMR resonance of the P=C carbon of 3.9a [δ(13C) = 203.3 1JPC = 48 Hz] is shifted downfield compared with the one of MesP=CPh2 [δ(13C) = 193.4, 1JPC = 44 Hz],17 but is similar to the one of MesP=CH(t-Bu) [δ(13C) = 203.3, 1JPC = 44 Hz].176 Interestingly, there is no significant difference in the 31P{1H} NMR chemical shifts when π-donating substituents are employed [i.e. 3.23a vs  70 3.9a, ∆δ(31P) = 1]. Previous studies of C-aryl phosphaalkenes, MesP=C(Ar)Ph and DPCB suggest significant π-conjugation between the P=C bond and the cis- and trans- configured aryl groups.68,76,99 The present results in contrast suggest that in PhAk–Ox proligands there is poor π conjugation between the cis-configured C-aryl substituent and the P=C bond. The introduction of inductively withdrawing substituents generates a downfield chemical shift [i.e. 3.24a to 3.22a, ∆δ(31P) = 11 (E)]. However, the magnitude of the chemical shift is smaller than expected for a π- conjugated phosphaalkene [i.e. C6H5–DPCB vs 3,5-(CF3)2C6H3–DPCB, ∆δ(31P) = 23]. In summary, both the NMR and the X-ray data are in accordance with minimal conjugation between the P=C bond and the C-aryl group, but the electronic properties of the P=C bond can be tuned by inductive effects. Table 3.1 31P{1H} and 13C{1H} NMR Chemical Shifts of Chiral Phosphaalkenes. R2 C P R1 R1 O N Ar  compd R1 / R2 Ar 31P NMR (δ) 13C NMR δ (1JPC Hz) 3.9a Me / Ph Mes 244 203.3(48) 3.9b Me / Ph 2,4,6-(i-Pr)3C6H2 248 201.3(56) 3.9c Me / Ph 2-i-PrC6H4 245 204.9(49) 3.9d Me / Ph 2-t-BuC6H4 254 196.7(50) 3.22a (CH2)4 / Ph Mes 243 200.8(47) 3.23a Me / 4-(MeO)C6H4 Mes 245 203.2(47) 3.24a (CH2)4 / 3,5-(CF3)2C6H3 Mes 254 196.9(50)  3.3.6 Preliminary Polymerization Data for Phosphaalkene–Oxazoline  Given our interest in the polymerization of P=C bonds, chiral 3.9a presented itself as a great monomer candidate for polymerization. Recently, phosphaalkenes have shown interesting applications in materials and polymer chemistry.177-185 We were interested in investigating the  71 suitability of phosphaalkene–oxazoline 3.9a as a polymer precursor. Heating 3.9a to its distillation temperature (ca. 200 ºC) yielded a viscous/gelatinous residue in the still pot. Analysis of this residue by 31P{1H} NMR spectroscopy revealed a broad resonance at δ(31P) = −13 that resembled other poly(methylenephosphine) polymers (Figure 3.4).185 The observed chemical shifts are consistent with the polymerization of the P=C bond and not of the oxazoline ring. Precipitation of 3.25 with hexanes from a saturated THF solution gave polymers with an absolute molecular weight (Mw) of 21 000 g·mol-1 by triple detection GPC. Polymers of type 3.25 have the potential to become a recyclable ligand source for asymmetric catalysis.184 Polymerization studies using anionic and radical initiators are presently underway and will be reported in due course.  C P O N i-Pr Mes n P C Mes Ph ! ON i-Pr n 3.9a 3.25  Figure 3.4 31P{1H}(121 MHz, CH2Cl2) NMR Spectrum of Polymer 3.25.  3.4 Conclusion We have reported a detailed study into the synthesis of enantiomerically pure phosphaalkenes with modifications to the carbon backbone and to the P-aryl substituent. Two unique mono-ortho-aryl substituted P-aryl phosphaalkenes were isolated and characterized. A  72 small set of PhAk–Ox ligands was synthesized and is available for screening in asymmetric catalysis. Analysis by NMR spectroscopy and X-ray crystallography both indicate that conjugation between the C-aryl group and the P=C bond is minimal. In addition, the P=C bond in PhAk–Ox’s can be thermally polymerized. Investigation of the coordination, catalytic, and polymerization properties of phosphaalkene–oxazoline is presently ongoing.  3.5 Experimental Section 3.5.1 General Procedures  All manipulations of air- and/or water- sensitive compounds were performed under a nitrogen atmosphere using standard Schlenk or glovebox techniques. Hexanes and dichloromethane (CH2Cl2) were deoxygenated with nitrogen and dried by passing through a column containing activated alumina. Tetrahydrofuran (THF) was dried over sodium and benzophenone. Ethyl benzoate, methyl 4-methoxybenzoate, isobutyric acid, L-valine, cyclopentane carboxylic acid, chlorotrimethylsilane, 2-isopropylaniline, 2-tert-butylaniline, magnesium and xylenes were purchased from Aldrich and used as received. Anhydrous hydrochloric acid was obtained from BOC gases and used as received. sec-Butyllithium and methyllithium were purchased from Aldrich and titrated using N-benzylbenzamide.186 N,N,N’,N’- tetramethylethylenediamine (TMEDA) was purchased from Aldrich and distilled over sodium prior to use. L-Valinol,163 oxazoline 3.7,162 and MesP(SiMe3)2187 were prepared according to literature procedures. 1H, 31P{1H}, 13C{1H} NMR spectra were recorded at 25 ºC on Bruker Avance 300 or 400 MHz spectrometers. 85% H3PO4 was used as an external standard (δ = 0.0 for 31P). 1H NMR spectra were referenced to residual protonated solvent and 13C NMR were referenced to the deuterated solvent. Elemental analyses were performed in the University of  73 British Columbia Chemistry Microanalysis Facility. Mass spectra were recorded on a Kratos MS 50 instrument in EI mode (70 eV). The optical rotations were measured at a concentration in g/100 mL and their values (average of 10 measurements) were obtained on a Jasco P-1010 polarimeter.  3.5.2 Spectroscopic Data of Mixture of 3.6a and 3.6b 31P{1H} NMR (121 MHz, CDCl3): δ 32 (d, 1JPP = 202 Hz), 32 (d, 1JPP = 196 Hz), 4 (d, 1JPP = 202 Hz), 0 (d, 1JPP = 196 Hz); 1H NMR (400 MHz, CDCl3): δ 7.41–6.79 (m, 18 H), 4.75–4.70 (m, 1H), 4.67–4.63 (m, 1H), 4.54–4.50 (m, 1H), 4.41–4.37 (m, 1H), 3.86–3.80 (m, 1H), 3.48– 3.41 (m, 1H), 2.62 (s, 3H), 2.55–2.51 (m, 21H), 2.27 (s, 3H), 2.26 (s, 3H), 2.23 (s, 3H), 2.22 (s, 3H), 2.11–2.03 (m, 1H), 1.80–1.70 (m, 1H), 1.01 (d, 3JHH = 7 Hz, 3H), 0.95 (d, 3JHH = 7 Hz, 3H), 0.90 (d, 3JHH = 7 Hz, 3H), 0.64 (d, 3JHH = 7 Hz, 3H).  3.5.3 Synthesis of (S)-PhC=OC(Me)2(CNOCH(i-Pr)CH2) (3.8) To a cooled (−78 ºC) solution of oxazoline 3.7 (10 g, 64 mmol) and TMEDA (7.4 g, 64 mmol) in THF (1 M) was added sec-butyllithium (1.27 M, 51 ml, 65 mmol). After 1 h at −78 ºC, ethyl benzoate (10.7 g, 71 mmol) was added to the reaction mixture. The solution was warmed to room temperature and stirred for 30 min. Subsequently, water (25 mL) and saturated aqueous ammonium chloride (25 mL) were added to the yellow reaction mixture. The aqueous layer was extracted with diethyl ether (3 × 150 mL). The organic fractions were combined, dried using sodium sulfate, and concentrated by rotary evaporation in vacuo. The residue was purified by  Paragraph has been removed for copyright reasons. The paragraph described the experimental details for co pound 3.8 it is found in the 3rd paragraph of the original source supporting information. Julien Dugal-Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.   74 bulb-to-bulb fractional distillation (155-165 ºC, 0.2 mmHg) to afford ketone 3.8 (8.2 g, 49%) as a colorless oil. [α]D22 = −28.1 (c 0.13, CHCl3).  1H NMR (400 MHz, CDCl3) δ 7.98–7.96 (m, 2H), 7.50–7.46 (m, 1H), 7.39–7.35 (m, 2H), 4.11–4.07 (m, 1 H), 3.97–3.90 (m, 1H), 3.88–3.83 (m, 1H), 1.84–1.73 (m, 1H) 1.60 (s, 3H), 1.58 (s, 3H), 0.97 (d, 3JHH = 7 Hz, 3H), 0.87 (d, 3JHH = 7 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 199.0, 170.2, 135.8, 132.7, 128.9, 128.4, 72.1, 70.6, 48.3, 32.5, 25.0, 24.9, 19.1, 18.2; IR (neat, NaCl): 1691, 1661, 1449 cm-1; MS (ESI): m/z [%] 283, 282 [15, 100, M + Na]+, 261, 260 [8, 38, M + H]+; HRMS calcd for C16H21NO2Na 282.1470; Found 282.1469; anal. calcd for C16H21NO2: C, 74.10; H, 8.16; N, 5.40; Found: C, 73.73; H, 8.27; N, 5.45. Table 3.2 COSY Data for Compound 3.8. O O N 1 2 3 4 5 6 7 8 9 10 11 12 13 1415 16  proton no. 1H δ  (ppm)(mult. J(Hz))a,b,c COSY correlation d H3/H7 7.98–7.96 (m) H4/H6; H5 H4/H6 7.39–7.35 (m) H3/H7; H5 H5 7.50–7.46 (m) H3/H7; H4/H6 H9e 1.58 (s) H10e 1.60 (s) H12 4.11–4.07 (m) H12’; H13 H12’ 3.97–3.90 (m) H12; H13 H13 3.88–3.83 (m) H14; H12’; H12 H14 1.78 (sept, 7) H15/H16; H13 H15e 0.97 (d, 7) H14 H16e 0.87 (d, 7) H14 a Recorded at 400 MHz. b Assignments made based on HMQC and COSY data. c H and H’ are assigned arbitrarily. d Only correlations which could be unambiguously assigned are recorded. e Arbitrarily assigned.  75  Table 3.3 NMR Data for Compound 3.8. O O N 1 2 3 4 5 6 7 8 9 10 11 12 13 1415 16  carbon no. 13C (ppm)a mult. 1H (ppm)(mult. J(Hz))b,c,d 1 199.0 Q 2 135.8 Q 3/7 128.9 CH H3/H7: 7.98-7.96 (m) 4/6 128.4 CH H4/H6: 7.39/7.35 5 132.7 CH H5: 7.50-7.46 (m) 8 48.3 Q 9e 24.9 CH3 H9: 1.60 (s) 10e 25.0 CH3 H10: 1.58 (s) 11 170.2 Q 12 70.6 CH2 H12: 4.11–4.07 (m) H12’: 3.97–3.90 (m) 13 72.1 CH H13: 3.88–3.83 (m) 14 32.5 CH H14: 1.78 (sept, 7) 15e 19.1 CH3 H15: 0.97 (d, 7) 16e 18.2 CH3 H16: 0.87(d, 7) a Recorded at 100 MHz. bRecorded at 400 MHz. c Assigments are based on HMQC data. d Only correlations which could be unambiguously assigned were recorded. e Arbitrarily assigned.  3.5.4 Synthesis of (S)-4-OMeC6H4C=OC(Me)2(CNOCH(i-Pr)CH2) (3.19) To a cooled (−78 ºC) solution of oxazoline 3.7 (7.39 g, 46.6 mmol) and TMEDA (7.2 mL, 47.5 mmol) in THF (50 mL) was added s-BuLi (1.24 M, 38 mL, 47.1 mmol). After stirring the reaction mixture at −78 ºC for 45 min, a solution of methyl 4-methoxybenzoate (7.98 g, 47.5 mmol) in THF (30 mL) was added cold and the reaction mixture was stirred for 1 h and warmed to room temperature. The reaction mixture was quenched with a solution of saturated NH4Cl (25 mL) and water (25 mL). The aqueous layer was extracted with Et2O (3 × 30 mL). The organic fractions were combined, dried using Na2SO4, and the solvent removed by rotary evaporation in  76 vacuo. The yellow oil was purified by bulb-to-bulb distillation under reduced pressure to afford ketone 3.19 (9.86 g, 72%) as a colorless oil. [α]D21 = −33.9 (c 0.326, CHCl3). 1H NMR (300 MHz, CDCl3): δ 7.97 (d, 3JHH = 9 Hz, 2H), 6.82 (d, 3JHH = 9 Hz, 2H), 4.08 (dd, 3JHH = 9 Hz, 3JHH = 7 Hz, 1H), 3.92–3.83 (m, 2H), 3.80 (s, 3H), 1.84–1.73 (m, 1H), 1.55 (s, 3H), 1.53 (s, 3H), 0.95 (d, 3JHH = 7 Hz, 3H), 0.85 (d, 3JHH = 7 Hz, 3H); 13C{1H} NMR (75MHz, CDCl3): δ 197.1, 170.5, 163.1, 131.3, 128.4, 113.5, 72.0, 70.5, 55.5, 48.0, 32.5, 25.1, 25.0, 19.1, 18.2; IR (thin layer): 2960, 2936, 2904, 2866, 1682, 1656, 1602, 1575, 1511 cm-1; HRMS calcd for C17H24NO3: 290.1756; Found: 290.1752.  3.5.5 Synthesis of (S)-2-cyclopentyl-4-isopropyl-4,5-dihydrooxazole (3.18) A modified literature procedure was used.162 To a solution of L-valinol (8.52 g, 82.6 mmol) in xylenes (0.5 M) was added cyclopentane carboxylic acid (9.1 mL, 82.6 mmol) and the mixture was heated to reflux using a Dean-Stark apparatus for 44 h. The reaction mixture was cooled and extracted with 10% aqueous hydrochloric acid solution and the aqueous layer was neutralized with 40% aqueous sodium hydroxide solution. The aqueous layer was extracted with Et2O (3 × 60 mL) and the combined organic extracts were dried using Na2SO4. The solvent was removed by rotary evaporation in vacuo, and the crude product was purified by bulb-to-bulb distillation (95 ºC, 0.4 mmHg) to yield 3.18 (8.27 g, 55%) as a colorless oil. [α]D22 = −62.5 (c 0.607, CHCl3).  1H NMR (CDCl3, 300 MHz): δ 4.17–4.11 (m, 1H), 3.88–3.79 (m, 2H), 2.76–2.65 (m 1H), 1.88–1.83 (m, 2H), 1.77–1.70 (m, 5H), 1.55–1.52 (m, 2H), 0.86 (d, 3J(H,H)=7 Hz, 3H), 0.77 (d, 3J(H,H)=7 Hz, 3H); 13C{1H} NMR (CDCl3, 75 MHz): δ 170.7, 71.8, 69.7, 38.4, 32.6,  77 30.7, 30.6, 25.9, 18.8, 17.8; IR (thin layer): 2958, 2872, 1666 cm-1; HRMS calcd for C11H20NO: 182.1545: Found: 182.1540.  3.5.6 Synthesis of (S)-PhC=OC(-C4H8-)(CNOCH(i-Pr)CH2) (3.20) To a solution of oxazoline 3.18 (5.00 g, 27.6 mmol) and TMEDA (4.2 mL, 27.7 mmol) in THF (30 mL) at −78 ºC was added s-BuLi solution (1.4 M, 20.0 mL, 28.0 mmol). After stirring the reaction mixture at −78 ºC for 1 h, ethyl benzoate (4.0 g, 27.5 mmol) in THF (15 mL) was added cold. The reaction mixture was stirred for 1 h and warmed to room temperature. The reaction mixture was stirred for 1 h and warmed to room temperature. The reaction mixture was quenched with a solution of saturated NH4Cl (50 mL) and water (10 mL). The aqueous layer was extracted with Et2O (3 × 50 mL). The organic fractions were combined, dried using Na2SO4, and the solvent removed by rotary evaporation in vacuo. The yellow oil was purified by flash column chromatography with silica (hexanes/EtOAc, 95:5) to obtaining ketone 3.20 (5.51 g, 70%) as a colorless oil. [α]D22 −19.9 (c 0.982, CHCl3). 1H NMR (300MHz, CDCl3): δ 7.87–7.84 (m, 2H), 7.32–7.26 (m, 1H), 7.21–7.16 (m, 2H), 3.89–3.86 (m, 1H), 3.74–3.60 (m, 2H), 2.35–2.10 (m, 4H), 1.65–1.46 (m, 5H), 0.77 (d, 3JHH = 7 Hz, 3H), 0.68 (d, 3JHH = 7 Hz, 3H); 13C{1H} NMR (75MHz, CDCl3): δ 196.5, 169.3, 135.2, 132.2, 128.7, 127.8, 71.5, 70.2, 58.2, 35.3, 35.2, 32.2, 25.7, 25.5, 18.5, 17.9; IR (thin layer): 3059, 2958, 2872, 1689, 1659, 1598, 1573 cm-1; HRMS calcd for C18H24NO2: 286.1807; Found: 286.1800.   78 3.5.7 Synthesis of (S)-3.5-(CF3)2C6H3C=OC(–C4H8–)(CNOCH(i-Pr)CH2) (3.21) To a solution of oxazoline 3.18 (0.34 g, 1.9 mmol) and TMEDA (0.3 mL, 1.8 mmol) in THF (19 mL) at -78 ºC was added s-BuLi solution (1.0 M, 2.0 mL, 2.0 mmol). After stirring the reaction mixture at −78 ºC for 1 h, a solution of N-methoxy-N-methyl-3,5- bis(trifluoromethyl)benzamide188 (0.56 g, 1.88 mmol) in THF (15 mL) was added cold. The reaction mixture was stirred for 1 h and warmed to room temperature. The reaction mixture was quenched with a solution of saturated NH4Cl (15 mL) and water (15 mL). The aqueous layer was extracted with Et2O (3 × 25 mL). The organic fractions were combined, dried using Na2SO4, and the solvent removed by rotary evaporation in vacuo. The yellow oil was purified by flash column chromatography with silica (hexanes/EtOAc, 95:5) to obtaining ketone 3.21 (0.71 g, 90%) as a colorless oil. [α]D22 −27.0 (c 1.04, CHCl3). 1H NMR (300 MHz, CDCl3) δ 8.46 (s, 2H), 8.00 (s, 1H), 4.15–4.06 (m, 1H), 3.87–3.77 (m, 2H), 2.51–2.23 (m, 4H), 1.91–1.52 (m, 5H), 0.92 (d, 3JHH = 7 Hz, 3H), 0.81 (d, 3JHH = 7 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 194.8, 168.8, 137.4, 132.1 (q, 2JFC = 34 Hz), 129.3 (q, 3JFC = 4 Hz), 125.9 (quint, 3JFC = 4 Hz), 123.2 (q, 1JFC = 271 Hz), 72.5, 71.2, 58.8, 35.8, 35.6, 32.9, 26.2, 26.1, 19.1, 18.3; IR (thin layer): 3088, 2962, 2876, 1703, 1661, 1615 cm-1; HRMS calcd for C20H22F6NO2: 422.1555; Found: 422.1547.  3.5.8 Synthesis of (S)-MesP=CPhC(Me)2(CNOCH(i-Pr)CH2) (3.9a) To a solution of MesP(SiMe3)2 (11.34 g, 38 mmol) in THF (25 mL) was added methyllithium (1.6 M, 24 mL, 38 mmol). The reaction mixture was heated to 55 ºC for 1–2 h. 31P{1H} NMR analysis of an aliquot removed from the reaction mixture suggested quantitative formation of MesP(Li)(SiMe3) (δ = −187 ppm). The reaction mixture was cooled to −78 ºC and Paragraph has been removed for copyright reasons. The paragraph detailed experimental procdure for compounds 3.9a and it is found in the 5th paragraph of the original source’s supporting information. Julien Dugal-Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA  79 treated with a solution of oxazoline 3.8 (9.93 g, 38 mmol) in THF (15 mL). After warming to room temperature, analysis of an aliquot removed from the reaction mixture by 31P{1H} NMR spectroscopy revealed a singlet resonance, which is consistent with phosphaalkene (3.9a) (δ = 244). The reaction mixture was quenched with Me3SiCl (4.14 g, 38 mmol), the solvent evaporated in vacuo, and the product was extracted into hexanes (1 × 20 mL, 2 × 10 mL). After filtration, the hexanes was removed in vacuo. The product was recrystallized from n-pentane to afford a colorless crystalline solid, which was washed with cold n-pentane (2 × 5 ml) and dried in vacuo (7.87 g, 52%). [α]D22 −65.8 (c 0.50, CDCl3). 31P{1H} NMR (121 MHz, CDCl3): δ 244; 1H NMR (400 MHz, CDCl3): δ 7.00–6.50 (m, 7H), 4.23–4.18 (m, 1H), 3.99–3.95 (m, 1H), 3.88–3.82 (m, 1H), 2.26 (s, 3H), 2.21 (s, 3H), 2.09 (s, 3H), 1.75–1.66 (m, 1H), 1.67 (d, 4JPH = 1 Hz 3H), 1.64 (d, 4JPH = 1 Hz, 3H), 0.90 (d, 3JHH = 7 Hz, 3H), 0.81 (d, 3JHH = 7 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 203.3 (d, 1JPC = 48 Hz), 170.6 (d, 3JPC = 6 Hz), 142.8 (d, JPC = 15 Hz), 140.0 (d, JPC = 7 Hz), 139.8 (d, JPC = 6 Hz), 137.9, 135.9 (d, 1JPC = 41 Hz), 128.0 (d, JPC = 4 Hz), 126.9, 126.7, 126.6, 126.3, 72.1, 70.0, 47.5 (d, 2JPC = 25 Hz), 32,6, 28.2 (d, JPC = 9 Hz), 28.0 (d, JPC = 7 Hz), 22.6 (d, JPC = 7 Hz), 22.5 (d, JPC = 7 Hz), 21.1, 19.2, 18.0; LRMS (EI): m/z [%] 394, 393 [4, 15, M+], 380, 379, 378 [12, 74, 100, M+ − CH3], 275, 274 [5, 24, M+ − Mes]; anal. calcd for C25H32NOP: C, 76.31; H, 8.20; N, 3.56; Found: C, 76.56; H, 8.17; N, 3.56. Paragraph has been removed for copyright reasons. The paragraph detailed experimental procdure for compounds 3.9a and it is found in 5th paragraph of the original source’s supporting information. Julien Dugal-Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.   80 Table 3.4 COSY Correlation for Compound 3.9a. C P O N1 23 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 20 22 2324 25  proton no. 1H δ  (ppm)(mult. J(Hz))a,b,c COSY correlation d H3/H5 6.58–6.54 (m) H7e 2.26 (s) H8 2.09 (s) H9e 2.21 (s) H12/H16 6.78–6.75 (m) H13/H15/H16 H13/H15 7.00–6.91 (m) H12/H16 H14 7.00–6.91 (m) H12/H16 H18e 1.67 (d, 1) H19e 1.64 (d, 1) H21 4.23–4.18 (m) H21’; H22 H21’ 3.99–3.95 (m) H21; H22 H22 3.88–3.82 (m) H21;H21’;H22 H23 1.75–1.66 (m) H22;H24/H25 H24e 0.90 (d, 7) H23 H25e 0.81 (d, 7) H23 a Recorded at 400 MHz. b Assignments made based on HMQC, HMBC and COSY data. c H and H’ are assigned arbitrarily. d Only correlations which could be unambiguously assigned are recorded. e Arbitrarily assigned.  81  Table 3.5 NMR Data for 3.9a. C P O N1 23 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 20 22 2324 25  carbon no. 13C (ppm)a (mult. J(Hz)) Mult. 1H (ppm)(mult. J(Hz))b,c,d HMBC Correlation 1 135.9 (d, 41) Q  H7/H9: 2.26 (s); 2.21 (s) 2e 140.0 (d, 7) Q  H7/H9: 2.26 (s) 3/5 128.0 (d, 4) CH H3/H5: 6.58–6.54 (m) H7/H9: 2.26 (s); 2.21 (s); H8: 2.09 (s); H3/H5: 6.58–6.54 (m) 4 137.9 Q  H8: 2.09 (s); H3/H5: 6.58–6.54 (m) 6e 139.8 (d, 6) Q  H7/H9: 2.21 (s) 7e 22.6 (d, 7) CH3 H7: 2.26 (s) 8 21.2 CH3 H8: 2.09 (s) 9e 22.5 (d, 7) CH3 H9: 2.21 (s) 10 203.3 (d, 48) Q  H12/H16: 6.78–6.75 (m) 11 142.8 (d, 15) Q  H13/H15: 7.00–6.91 (m) 12e 126.7 CH H12/H16: 6.78–6.75 (m) H12/H16: 6.78–6.75 (m) 13/15 126.9 CH H13/H15: 7.00–6.91 (m) H13/H15/H16: 7.00–6.91 (m) 14 126.3 CH H14: 7.00–6.91 (m) H12/H16: 6.78–6.75 (m) 16e 126.6 CH H12/H16: 6.78–6.75 (m) H12/H16: 6.78–6.75 (m) 17 47.5 (d, 25) Q  H18/H19: 1.67 (d, 1); 1.64 (d, 1) 18e 28.2 (d, 9) CH3 H18: 1.67 (d, 1) H19: 1.64 (d, 1) 19e 28.0 (d, 7) CH3 H19: 1.64 (d, 1) H18: 1.67 (d, 1) 20 170.6 (d, 6) Q H21: 4.23–4.18 (m); H21’: 3.99–3.95 (m); H22: 3.88– 3.82 (m) 21 70.0 CH2 H21: 4.23–4.18 (m); H21’: 3.99–3.95 (m) 22 72.1 CH H22: 3.88–3.82 (m) H24/H25: 0.90 (d, 7); 0.81 (d, 7); H21’: 3.99–3.95 (m) 23 32.6 CH H23: 1.75–1.66 (m) H24/H25: 0.90 (d, 7); 0.81 (d, 7); H21: 4.23–4.18 (m); H21’: 3.99–3.95 (m) 24e 19.2 CH3 H24: 0.90 (d, 7) H25: 0.81 (d, 7) 25e 18.0 CH3 H25: 0.81 (d, 7) H24: 0.90 (d, 7) a Recorded at 100 MHz. bRecorded at 400 MHz. c Assigments are based on HMQC data. d Only correlations which could be unambiguously assigned were recorded. e Arbitrarily assigned.  82  3.5.9 Synthesis of (S)-2,4,6-(i-Pr)3C6H2P=CPhC(Me)2(CNOCH(i-Pr)CH2) (3.9b) To a solution of 2-4-6-(i-Pr)3C6H2P(SiMe3)2189 (1.0 g, 2.6 mmol) in THF (5 mL) was added methyllithium (1.5 M, 1.75 mL, 2.6 mmol). The reaction mixture was heated to 55 ºC for 1-2 h. 31P{1H} NMR analysis of an aliquot removed from the reaction mixture suggested quantitative formation of 2-4-6-(i-Pr)C6H2P(Li)(SiMe3) (δ = −205 ppm). The reaction mixture was cooled to −78 ºC and treated with a solution of oxazoline 3.8 (0.68 g, 2.6 mmol) in THF (5 mL). After warming to room temperature, analysis of an aliquot removed from the reaction mixture by 31P{1H} NMR spectroscopy revealed a singlet resonance, which is consistent with phosphaalkene (3.9b) (δ = 248). The reaction mixture was quenched with Me3SiCl (0.286 g, 2.6 mmol), the solvent evaporated in vacuo, and the product was extracted into hexanes (1 × 10 mL, 2 × 5 mL). After filtration, the hexanes was removed in vacuo and the product was a yellow oil to obtain phosphaalkene 3.9b (1.2 g, 93%). [α]D18 −32.9 (c 2.4, CH2Cl2). 31P{1H} NMR (121 MHz, CDCl3): δ 248; 1H NMR (400 MHz, CDCl3): δ 7.00–6.62 (m, 7H), 4.25–4.16 (m, 1H), 4.01–3.94 (m, 1H), 3.92–3.83 (m, 1H), 3.40–3.25 (m, 2H), 2.68 (sept, 3JHH = 7 Hz 1H), 1.76–1.58 (m, 1H), 1.67 (s, 3H), 1.65 (s, 3H), 1.28-1.06 (m, 18H), 0.90 (d, 3JHH = 7 Hz, 3H), 0.82 (d, 3JHH = 7 Hz, 3H); HRMS calcd for C31H44NOP: 477.3161; Found: 477.3159; LRMS (EI): 479, 478, 477 [1, 3, 10, M+], 464, 463, 462 [6, 32, 100, M+ − CH3], 275, 274 [7, 23, M+ − (i-Pr)3C6H2].   83 3.5.10 Synthesis of 2-i-PrC6H4PCl2 (3.11) To a solution of Mg (2.97 g, 122 mmol) in THF (150 mL), was added 2-i-PrC6H4Br (20.3 g, 102 mmol). After 30 min the Grignard activated and the solution was refluxed for an additional 2 h. The mixture was cooled to rt and treated with ClP(NEt2)2169 (23.6 g, 112 mmol) and washed with THF (5 mL). The solvent was removed in vacuo, and the phosphine was extracted with hexanes (1 × 100 mL, 2 × 80 mL). The hexanes were removed in vacuo leaving crude 2-i-PrC6H4P(NEt2)2 as a colorless liquid with 31P{1H} NMR singlet resonance of 94 ppm. The crude solution containing 2-i-PrC6H4P(NEt2)2 in CH2Cl2 (150 mL) was treated with gaseous dry HCl and the mixture became darker, cloudy and then clear. 31P{1H} NMR analysis of an aliquot removed from the reaction mixture indicated 2 signals at 221 ppm (PCl3) and 167 ppm (2-i-PrC6H4PCl2). CH2Cl2 was evaporated in vacuo. The yellow solid was extracted with toluene (3 × 60 mL), filtered and the solvent was removed in vacuo. The crude product was purified by vacuum distillation 95 ºC (0.01 mmHg) to afford 3.12 (15.5 g, 69%) as a colorless liquid. 31P{1H} NMR (162 MHz, CDCl3): δ 164 (s); 1H NMR (400 MHz, CDCl3): δ 8.15–8.11 (m, 1H), 7.55–7.51 (m, 1H), 7.42–7.38 (m, 2H), 3.76 (sept, 3JHH = 7 Hz, 1H), 1.36 (d, 3JHH = 7 Hz, 6 H); 13C{1H} NMR (100 MHz, CDCl3): δ 151.8 (d, JPC = 31 Hz), 137.2 (d, JPC = 56 Hz), 133.1, 130.6 (d, JPC = 7 Hz), 127.2 (d, JPC = 1 Hz), 125.7 (d, JPC = 3 Hz), 31.1 (d, JPC = 33 Hz), 24.4; LRMS (EI): m/z [%] 224, 222, 220 [7, 42, 66, M+], 209, 207, 205 [3, 15, 23, M+ − CH3], 187, 186, 185 [10, 9, 32, M+ − Cl]; anal. calcd for C9H11Cl2P: C, 48.90; H, 5.02; Found: C, 48.84; H, 5.02.   84 3.5.11 Synthesis of 2-t-BuC6H4PCl2 (3.13) Same procedure as above for 3.12. Used 2-t-BuC6H4Br (8.47 g, 40 mmol), Mg (1.16 g, 48 mmol) and PCl(NEt3)2 (9.27 g, 44 mmol). The crude product was purified by vacuum distillation 110 ºC (0.01 mmHg) to afford 3.13 (7.4 g, 78%) as a colorless liquid. 31P{1H} NMR (121 MHz, CDCl3): δ 166 (s); 1H NMR (400 MHz, CDCl3): δ 8.36–8.31 (m, 1H), 7.46–7.36 (m, 3H), 1.57 (s, 9H); 13C{1H} NMR (121 MHz, CDCl3): δ 153.5 (d, JPC = 28 Hz), 140.4 (d, JPC = 68 Hz), 134.9, 132,4, 127.5, 125.2, 37.0, 33.7; HRMS (EI): calcd for C10H13Cl2P 234.0132; Found: 234.0131; LRMS (EI): m/z [%] 236, 235, 234 [43, 24, 68, M+], 221, 220, 219 [18, 4, 27, M+ − Me], 201, 200, 199 [14, 10, 45, M+ − Cl], 147 [100, M+ − CH5Cl2], 133 [22, M+ − PCl2]; anal. calcd for C10H13Cl2P: C, 51.09; H, 5.57; Found: C, 50.97; H, 5.60.  3.5.12 Synthesis of 2-i-PrC6H4PH2 (3.14) To a cooled (−78 ºC) solution of LiAlH4 (2.1 g, 56 mmol) in Et2O (300 mL) was added a solution of 3.12 (15.5 g, 70 mmol) in Et2O (15 mL). The cooling bath was removed and the solution was warmed to room temperature. 31P NMR analysis of an aliquot removed from the reaction mixture showed triplet resonance at −129 ppm. Degassed water (100 mL) was added to quench residual aluminum hydride. CAUTION: extreme care should be taken when adding the first few mL of water since quenching is highly exothermic and H2 is evolved. The ether layer was removed and the aqueous layer extracted with Et2O (150 mL, 100 mL). The organic layers were combined and the solvent removed in vacuo. The crude product was purified by vacuum distillation 60 ºC (0.01 mmHg) to afford 3.14 (7.5 g, 70%) as colorless liquid. CAUTION: The product is pyrophoric and very malodorous.  85 31P NMR (162 MHz, CDCl3): δ −127 (t, JPH = 203 Hz); 1H NMR (400 MHz, CDCl3): δ 7.53–7.48 (m, 1H), 7.34–7.26 (m, 2H), 7.13–7.06 (m, 1H), 3.96 (d, JPH = 203 Hz, 2H), 3.28 (sept, 3JHH = 7 Hz, 1H), 1.29 (d, 3JHH = 7 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 152 (d, JPC = 13 Hz), 136 (d, JPC = 7 Hz), 129, 128 (d, JPC = 8 Hz), 126 (d, JPC = 3 Hz), 125 (d, JPC = 3Hz) 33 (d, JPC=15 Hz), 24; LRMS (EI): m/z [%] 153, 152 [11,100, M+], 138, 137 [4, 33, M+ − Me] 120, 119 [4, 13, M+ − PH2], 111, 110 [9, 82, M+ − C3H6], 91 [40, C7H7+].  3.5.13 Synthesis of 2-t-BuC6H4PH2 (3.15) Same procedure as above for 3.14. Used 3.13 (7.2 g, 31 mmol) and LiAlH4 (0.873g, 23 mmol). The crude product was purified by vacuum distillation 60 ºC (0.01 mmHg) to afford title compound (4.17 g, 82%) as a colorless liquid. 31P NMR (162 MHz, CDCl3): δ −107 (t, 1JPH = 202 Hz); 1H NMR (400 MHz, CDCl3): δ 7.58–7.53 (m, 1H), 7.47–7.42 (m, 1H), 7.29–7.23 (m, 1H), 7.11–7.05 (m, 1H), 4.21 (d, 1JPH=203 Hz, 2H), 1.52 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3): δ 154.3 (d, JPC = 15 Hz), 140.0, 128.7, 127.8 (d, JPC = 17 Hz), 126.6 (d, JPC = 5 Hz), 125.8, 36.9, 31.3 (d, JPC = 11 Hz); HRMS calcd for C10H15P: 166.0911, Found: 166.0908; LRMS (EI): m/z [%] 167, 166 [7, 62, M+], 165 [100, M+ − H], 152, 151 [5, 56, M+ − Me], 134, 133 [3, 16, M+ − PH2], 110, 109 [13, 44, M+ − t-Bu], 57 [28, t-Bu+].  3.5.14 Synthesis of 2-i-PrC6H4P(SiMe3)2 (3.16) To a cooled solution (−78 ºC) of 3.14 (7.0 g, 46 mmol) in THF (100 mL) was added MeLi in Et2O (1.45 M, 70 mL, 101 mmol). The reaction mixture was warmed to room  86 temperature and stirred for 1 h whereafter the solution was cooled (−78 ºC) and treated with Me3SiCl (13.5 mL, 106 mmol). 31P{1H} NMR analysis of an aliquot removed from the reaction mixture revealed the presence of 2-i-PrC6H4P(SiMe3)2 at −153 ppm. Often, after the first lithiation a mixture of 2-i-PrC6H4P(SiMe3)2 and 2-i-PrC6H4PH(SiMe3) was observed. In this instance, the reaction mixture was relithiated (20 mL) and silylated (3.6 mL) following the above procedure. Typically, after one relithiation 3.16 was formed quantitatively (31P{1H} NMR spectroscopy). The solvent was removed in vacuo. The yellow solid was extracted with hexanes (2 × 100 mL, 50 mL), filtered and the solvent removed. The crude product was purified by vacuum distillation (113 ºC, 0.01 mmHg) afforded title compound (6.6 g, 48%) as a colorless liquid. 31P{1H} NMR (162 MHz, CDCl3): δ −153 (s); 1H NMR (400 MHz, CDCl3): δ 7.50–7.46 (m, 1H), 7.34–7.25 (m, 2H), 7.10–7.04 (m, 1H), 3.98 (sept, 3JHH = 7 Hz, 1H), 1.25 (d, 3JHH = 7 Hz, 6H), 0.30 (s, 9H), 0.28 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3): δ 155.6 (d, JPC = 22 Hz), 138.5 (d, JPC = 6 Hz), 130.3 (d, JPC = 12 Hz), 128.1, 125.6 (d, JPC = 6 Hz), 124.9, 32.2 (d, JPC = 24 Hz), 23.9, 1.6, 1.4; HRMS calcd for C13H29PSi2: 296.1546; Found: 296.1547; LRMS (EI): m/z [%] 297, 296 [6, 21, M+], 282, 281 [2, 6, M+ − Me], 224, 223 [4, 10, M+ − SiMe3], 75, 74, 73 [4, 8, 100, SiMe3]; anal. calcd for C15H29PSi2: C, 60.76; H, 9.86; Found: C, 60.42; H, 9.84.  3.5.15 Synthesis of 2-t-BuC6H4P(SiMe3)2 (3.17) Same procedure as above for 3.16. Used 3.15 (4.1 g, 25 mmol), MeLi in Et2O (1.5 M, 33 mL, 50 mmol) and TMSCl (6.3 mL, 50 mmol). The crude product was purified by vacuum distillation (130 ºC, 0.01 mmHg) to afford title compound (5.65 g, 72%) as a colorless liquid.  87 31P{1H} NMR (162 MHz, CDCl3): δ –134 (s); 1H NMR (400 MHz, CDCl3): δ 7.57–7.53 (m, 1H), 7.48–7.43 (m, 1H), 7.25–7.19 (m, 1H), 7.09–7.03 (m, 1H), 1.62 (d, JPH = 1 Hz 9H), 0.29 (s, 9H), 0.28 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3): δ 156.7 (d, JPC = 18 Hz), 142.6 (d, JPC = 6 Hz), 130.8 (d, JPC = 22 Hz), 127.7, 126.6 (d, JPC = 8 Hz), 124.6, 37.4, 32.0 (d, JPC = 11 Hz), 1.9, 1.8; HRMS calcd for C16H31PSi2: 310.1702; Found: 310.1701; LRMS (EI): m/z (EI) 312, 311, 310 [2, 9, 32, M+], 296, 295 [3, 9, M+ − Me], 239, 238, 237 [4, 10, 49, M+ − SiMe3], 74, 73 [7, 100, SiMe3+]; anal. calcd for C16H31PSi2: C, 61.88; H, 10.06; Found: C, 61.90; H, 10.09.  3.5.16 Synthesis of (S)-2-i-PrC6H4P=CPhC(Me)2(CNOCH(i-Pr)CH2) (3.9c) To a solution of 2-i-PrC6H4P(SiMe3)2 (1.0g, 3.3 mmol) in THF (10 mL) was added MeLi in Et2O (1.5 M, 2.25 ml, 3.3 mmol). The reaction mixture was heated to 55 ºC for 1–2 h. The solution was cooled at −78 ºC and treated with a THF (5 ml) solution of PhCOCMe2(CNOCH(i- Pr)CH2) (855 mg, 3.3 mmol). After warming to room temperature, analysis of an aliquot removed from the reaction mixture by 31P{1H} NMR spectroscopy revealed a singlet resonance, which was assigned as a phosphaalkene (δ = 245). The reaction mixture was quenched with Me3SiCl (356 mg, 3.3 mmol), the solvent evaporated in vacuo and the product was extracted into hexanes (3 × 10 ml). The solvent was removed in vacuo and the phosphaalkene was purified by bulb-to-bulb distillation (0.01 mmHg) to afford phosphaalkene 3.9c (1.1 g, 85%) as a yellow oil. [α]D27 −88.2 (c 1.9, CH2Cl2). 31P{1H} NMR (121 MHz, CDCl3): δ 245; 1H NMR (400 MHz, CDCl3): δ 7.07–6.71 (m, 9H), 4.25–4.18 (m, 1H), 4.01–3.94 (m, 1H), 3.90–3.81 (m, 1H), 3.37–3.27 (m, 1H), 1.76–1.59 (m, 1H), 1.70 (s, 3H), 1.68 (s, 3H), 1.25–1.20 (m, 6H), 0.93 (d, 3JHH = 7 Hz, 3H), 0.84 (d, 3JHH =  88 7 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 204.9 (d, 1JPC = 49 Hz), 170.4 (d, JPC = 8 Hz), 151.4 (d, JPC = 9Hz), 141.9 (d, JPC = 14 Hz), 139.0 (d, 1JPC = 41 Hz), 133.5 (d, JPC = 5 Hz), 128.8, 128.5, 128.4, 127.0, 126.3, 125.0 (d, JPC = 2 Hz), 124.5, 72.1, 70.0, 47.6 (d, 2JPC = 25 Hz), 32.8 (d, JPC = 11 Hz), 32.6, 28.0, 27.8, 23.9, 23.8, 19.2, 18.1; HRMS calcd for C23H32NOP: 393.2222; Found: 393.2220; LRMS (EI): m/z [%]: 394, 393 [5, 12, M+], 380, 279, 378 [4, 27, 100, M+ − Me]; anal. calcd for C25H32NOP: C, 76.31; H, 8.20; N, 3.56; Found: C, 76.62; H, 8.34, N, 3.66.  Table 3.6 COSY Correlation for Compound 3.9c. C P O N1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 19 21 20 22 23 24 25 18  proton no. 1H δ  (ppm)(mult. J(Hz))a,b,c COSY correlation d H2 H2: 6.91–6.86 (m) H3 H3 H3: 6.79–6.73 (m) H2; H4 H4 H4: 7.07–7.00 (m) H3 H5 H5: 7.07–7.00 (m) H7 3.37–3.28 (m) H8/H9 H8e 1.21 (d, 7) H7 H9e 1.20 (d, 7) H7 H12/H16 H12/H16: 6.79–6.73 (m) H13/H15 H13/H15 H13/H15: 6.99–6.95 (m) H12/H16; H14 H14 H14: 6.95–6.93 (m) H13/H15 H18e 1.70 (s) H19e 1.68 (s) H21 4.25–4.18 (m) H21’; H22 H21’ 4.01–3.94 (m) H21; H22 H22 3.90–3.81 (m) H21; H21’ H23 1.76–1.59 (m) H24/H25 H24e 0.90 (d, 7) H23 H25e 0.81 (d, 7) H23 a Recorded at 400 MHz. b Assignments made based on HMQC, HMBC and COSY data. c H and H’ are assigned arbitrarily. d Only correlations which could be unambiguously assigned are recorded. e Arbitrarily assigned.  89 Table 3.7 NMR Data for Compound 3.9c. C P O N1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 19 21 20 22 23 24 25 18  carbon no. 13C (ppm)a (mult. J(Hz)) mult. 1H (ppm) (mult. J(Hz))b,c,d HMBC correlation 1 139.0 (d, 41) Q  H7: 3.37–3.28 (m); H5: 7.07–7.00 (m) 2 133.5 (d, 5) CH H2: 6.91–6.86 (m) H4: 7.07–7.00 (m) 3 125.0 (d, 2) CH H3: 6.79–6.73 (m) 4 128.8 CH H4: 7.07–7.00 (m) H2: 6.91–6.86 (m) 5 124.5 CH H5: 7.07–7.00 (m) H7: 3.37–3.28 (m); H3: 6.79–6.73 (m) 6 151.4 (d, 9) Q H8/H9: 1.21 (d, 7); 1.20 (d, 7); H7: 3.37–3.28 (m); H2: 6.91– 6.86; H4: 7.07–7.00 (m) 7 32.8 (d, 11) CH H7: 3.37–3.28 (m) H8/H9: 1.21 (d, 7); 1.20 (d, 7) 8e 23.9 CH3 H8: 1.20 (d, 7) H9: 1.21 (d, 7); H7: 3.37–3.28 (m) 9e 23.8 CH3 H9: 1.21 (d, 7) H8: 1.20 (d, 7); H7: 3.37–3.28 (m) 10 204.9 (d, 49) Q  H18/H19: 1.70 (s); 1.68 (s) 11 141.9 (d, 14) Q  H13/H15: 6.99–6.95 (m) 12e 128.5 CH H12/H16: 6.79–6.73 (m) H13/H15: 6.99–6.95 (m); H12/H16: 6.79–6.73 13/15 127.0 CH H13/H15: 6.99–6.95 (m) H13/H15: 6.99–6.95 (m) 14 126.3 CH H14: 6.95–6.93 (m) H12/H16: 6.79–6.73 16e 128.4 CH H12/H16: 6.79–6.73 (m) H13/H15: 6.99–6.95 (m); H12/H16: 6.79–6.73 17 47.6 (d, 25) Q  H18/H19: 1.70 (s); 1.68 (s) 18e 28.0 CH3 H18/H19: 1.70 (s); 1.68 (s) H18/H19: 1.70 (s); 1.68 (s) 19e 27.8 CH3 H18/H19: 1.70 (s); 1.68 (s) H18/H19: 1.70 (s); 1.68 (s) 20 170.4 (d, 6) Q H18/H19: 1.70 (s); 1.68 (s); H21: 4.25–4.18 (m); H21’: 4.01– 3.94 (m); H22: 3.90–3.81 (m) 21 70.0 CH2 H21: 4.25–4.18 (m) H21’: 4.01–3.94 (m) H23: 1.76–1.59 (m) 22 72.1 CH H22: 3.90–3.81 (m) H24/H25: 0.81 (d, 7); H23: 1.76–1.59 (m); H21’: 4.01–3.94 (m) 23 32.6 CH H23: 1.76–1.59 (m) H24/H25: 0.81 (d, 7); H21: 4.25–4.18 (m); H21’: 4.01–3.94 (m); H22: 3.90–3.81 (m) 24e 19.2 CH3 H24: 0.90 (d, 7) H25: 0.81 (d, 7); H22: 3.90–3.81 (m) 25e 18.1 CH3 H25: 0.81 (d, 7) H24: 0.90 (d, 7) a Recorded at 100 MHz. bRecorded at 400 MHz. c Assigments are based on HMQC data. d Only correlations which could be unambiguously assigned were recorded. e Arbitrarily assigned.  90 3.5.17 Synthesis of (S)-2-t-BuC6H4P=CPhC(Me)2(CNOCH(i-Pr)CH2) (3.9d) To a solution 2-t-BuC6H4P(SiMe3)2 (1.1g, 3.2 mmol) in THF (10 mL) was added MeLi in Et2O (1.5 M, 2.1 mL, 3.2 mmol). The reaction mixture was heated to 55 ºC for 1–2 h. The solution was cooled at −78 ºC and treated with a THF (5 ml) solution of PhCOCMe2(CNOCH(i- Pr)CH2) (855 mg, 3.3 mmol). After warming to room temperature, analysis of an aliquot removed from the reaction mixture by 31P{1H} NMR spectroscopy revealed a singlet resonance, which was assigned as a phosphaalkene (δ = 254). The reaction mixture was quenched with Me3SiCl (347 mg, 3.2 mmol), the solvent evaporated in vacuo and the product was extracted into hexanes (3 × 10 ml). The solvent was removed in vacuo and the phosphaalkene was purified by bulb-to-bulb distillation (0.01 mmHg) to afford phosphaalkene 3.9d (1.2 g, 83%) as a yellow oil. [α]D27 −64.5 (c 1.7, CH2Cl2). 31P{1H} NMR (121 MHz, CDCl3): δ 254; 1H NMR (400 MHz, CDCl3): δ 7.22–7.15 (m. 1H), 7.05–6.88 (m, 5H), 6.83–6.77 (m, 2H), 6.73–6.67 (m, 1H), 4.25–4.17 (m, 1H), 4.02–3.95 (m, 1H), 3.87–3.83 (m, 1H), 1.79–1.65 (m, 1H), 1.66 (d, JPH = 2 Hz, 3H), 1.63 (d, JPH = 2 Hz, 3H), 1.51 (s, 9H), 0.90 (d, 3JHH = 7 Hz, 3H), 0.82 (d, 3JHH = 7 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 196.7 (d, 1JPC = 50 Hz), 170.7 (d, 3JPC = 8 Hz), 153.1 (d, JPC = 9 Hz), 142.0 (d, JPC = 14 Hz), 139.6 (d, 1JPC = 52 Hz), 136.4, 128.6 (d, JPC = 8 Hz), 128.2, 126.9, 126.1, 125.2, 124.7, 72.1, 69.9, 47.3 (d, 2JPC = 26 Hz), 37.0, 32.5 (d, JPC = 10 Hz), 28.1 (d, JPC = 6 Hz) 27.9 (d, JPC = 3 Hz), 19.2, 18.0; HRMS calcd for C26H34NOP: 407.2378; Found: 407.2380; LRMS (EI): m/z [%]: 408, 407 [4, 7, M+], 394, 393, 392 [5, 37, 100, M+ – t-Bu], 275, 274 [7, 23, M+ – t-Bu(C6H4)]; anal. calcd for C26H34NOP: C, 76.63; H, 8.41; N, 3.44; Found: C, 76.34; H, 8.78, N, 3.61.   91 3.5.18 Synthesis of (S)-MesP=C(4-OMeC6H4)C(Me)2(CNOCH(i-Pr)CH2) (3.23a) To a solution of MesP(SiMe3)2 (5.4 g, 18 mmol) in THF (25 mL) was added methyllithium (1.6 M, 11.3 mL, 18 mmol). The reaction mixture was heated to 55 ºC for 1–2 h. 31P{1H} NMR analysis of an aliquot removed from the reaction mixture suggested quantitative formation of MesP(Li)(SiMe3) (δ = −187 ppm). The reaction mixture was cooled to −78 ºC and treated with a solution of oxazoline 3.8 (5.0 g, 18 mmol) in THF (15 mL). After warming to room temperature, analysis of an aliquot removed from the reaction mixture by 31P{1H} NMR spectroscopy revealed a singlet resonance, which is consistent with phosphaalkene (3.23a) [δ(31P) = 245]. The reaction mixture was quenched with Me3SiCl (1.97 g, 18 mmol), the solvent evaporated in vacuo, and the product was extracted into hexanes (1 × 20 mL, 2 × 10 mL). After filtration, the hexanes was removed in vacuo and the product was bulb-to-bulb distilled to give phosphaalkene 3.23a (3.8, 50%) as a yellow oil. [α]D19 −80.8 (c 1.1, CH2Cl2). 31P{1H} NMR (121 MHz, CDCl3): δ 245; 1H NMR (400 MHz, CDCl3): δ 6.73–6.47 (m, 6H), 4.23–4.16 (m, 1H), 3.98–3.94 (m, 1H), 3.90–3.82 (m, 1H), 3.66 (s, 3H), 2.25 (s, 3H), 2.20 (s, 3H), 2.12 (s, 3H), 1.77–1.69 (m, 1H), 1.67 (s, 3H), 1.62 (s, 3H), 0.91 (d, 3JHH = 7 Hz, 3H), 0.82 (d, 3JHH = 7 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 203.2 (d, 1JPC = 48 Hz), 170.8 (d, JPC = 8 Hz), 158.0, 140.0 (d, JPC = 6 Hz), 139.8 (d, JPC = 6 Hz), 137.9, 136.1 (d, 1JPC = 43 Hz), 135.4 (d, JPC = 15 Hz), 128.1 (d, JPC = 6 Hz), 127.9 (d, JPC = 9 Hz), 112.4, 72.0, 69.9, 55.3, 47.6 (d, JPC = 26 Hz), 32.6, 28.3 (d, JPC = 5 Hz), 28.1, 22.6 (d, JPC = 8 Hz), 22.5 (d, JPC = 8 Hz), 21.2, 19.2, 18.0; HRMS calcd for C26H34NO2P: 423.2327; Found: 423.2322; LRMS (EI): m/z 424, 423 [6, 8, M+], 410, 409, 408 [6, 30, 100, M+ – Me].  92 Table 3.8 COSY Correlation for Compound 3.23a. C P O N1 23 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 20 22 23 24 25 O Me 26  proton no. 1H δ  (ppm)(mult. J(Hz))a,b,c COSY correlation d H3/H5 6.61–6.58 (m) H7e 2.25 (s) H8 2.12 (s) H9e 2.20 (s) H12/H16 6.54–6.48 (m) H13/H15 H13/H15 6.72–6.67 (m) H12/H16 H17 3.66 (s) H19e 1.67 (s) H20e 1.62 (s) H22 4.23–4.16 (m) H22’/H23 H22’ 3.98–3.94 (m) H22/H23 H23 3.90–3.82 (m) H22/H22’ H24 1.77–1.69 (m) H25/H26 H25e 0.91 (d, 7) H24 H26e 0.82 (d, 7) H24 a Recorded at 400 MHz. b Assignments made based on HMQC, HMBC and COSY data. c H and H’ are assigned arbitrarily. d Only correlations which could be unambiguously assigned are recorded. e Arbitrarily assigned.  93 Table 3.9 NMR Data for Compound 3.23a. C P O N1 23 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 20 22 23 24 25 O Me 26  carbon no. 13C (ppm)a (mult. J(Hz)) mult. 1H (ppm) (mult. J(Hz))b,c,d HMBC correlation 1 136.1 (d, 43) Q 2e 140.0 (d, 6) Q  H7: 2.25 (s) 3/5 128.1 (d, 6) CH H3/H5: 6.61–6.58 (m) H7/H9: 2.20 (s); 2.25 (s); H8: 2.12 (s) 4 137.9 Q  H8: 2.12 (s) 6e 139.8 (d, 6) Q  H9: 2.20 (s) 7e 22.6 (d, 8) CH3 H7: 2.25 (s) 8 21.2 CH3 H8: 2.12 (s) 9e 22.5 (d, 8) CH3 H9: 2.20 (s) 10 203.2 (d, 48) Q  H19/H20: 1.62 (s); 1.67 (s) 11 135.4 (d, 15) Q  H12/H16: 6.54–6.48 (m) 12/16 112.4 CH H12/H16: 6.54–6.48 (m) H13/H15: 6.72–6.67 (m) 13/15 127.9 (d, 9) CH H13/H15: 6.72–6.67 (m) H12/H16: 6.54–6.48 (m) 14 158.0 Q H17: 3.66 (s); H12/H16: 6.54–6.48 (m); H13/H15: 6.72–6.67 (m) 17 55.3 CH3 H17: 3.66 (s) 18 47.6 (d, 26) Q 19e 28.1 CH3 H19: 1.62 (s) H20: 1.67 (s) 20e 28.3 (d, 5) CH3 H20: 1.67 (s) H19: 1.62 (s) 21 170.8 (d, 8) Q  H19/H20: 1.62 (s); 1.67 (s) 22 69.9 CH2 H22: 4.23–4.16 (m); H22’: 3.98–3.94 (m) 23 72.0 CH H23: 3.90–3.82 (m) 24 32.6 CH H24: 1.77–1.69 (m) H25/H26: 0.91 (d, 7); 0.82 (d, 7) 25e 19.2 CH3 H25: 0.91 (d, 7) H26: 0.82 (d, 7) 26e 18.0 CH3 H26: 0.82 (d, 7) H25: 0.91 (d, 7) a Recorded at 100 MHz. bRecorded at 400 MHz. c Assigments are based on HMQC data. d Only correlations which could be unambiguously assigned were recorded. e Arbitrarily assigned.   94 3.5.19 Synthesis of (S)-MesP=CPhC(-C4H8-)(CNOCH(i-Pr)CH2) (3.22a) To a solution of MesP(SiMe3)2 (935 mg, 3.15 mmol) in THF (10 mL) was added MeLi in Et2O (1.1 M, 2.8 mL, 3.15mmol). The reaction mixture was heated to 55 ºC for 1–2 h. An aliquot was removed for 31P{1H} NMR analysis of an aliquot removed from the reaction mixture revealed a single resonance (δ = −187) assigned as MesP(SiMe3)Li. The solution was cooled at −78 ºC and treated with a THF (5 ml) solution of PhCOC(-C4H8-)(CNOCH(i-Pr)CH2) (901 mg, 3.15 mmol). After warming to room temperature, analysis of an aliquot removed from the reaction mixture by 31P{1H} NMR spectroscopy revealed a singlet resonance, which was assigned as a phosphaalkene (δ = 243). The reaction mixture was quenched with Me3SiCl (342 mg, 3.2 mmol), the solvent evaporated in vacuo and the product was extracted into hexanes (3 × 10 ml). The solvent was removed in vacuo and the phosphaalkene (S)-MesP=CPhC(-C4H8- )(CNOCH(i-Pr)CH2) (3.22a) was an impure yellow oil. 31P{1H} NMR (121 MHz, THF): δ 243. The solvent was removed in vacuo and the phosphaalkene was purified by bulb-to-bulb distillation (0.01 mmHg). (820 mg, 50%). [α]D18 −41.0 (c 1.3, CH2Cl2). 31P{1H} NMR (121 MHz, CDCl3): δ 245; 1H NMR (400 MHz, CDCl3): δ 6.99–6.93 (m, 3H), 6.81–6.77 (m, 2H), 6.62–6.57 (m, 2H), 4.19–4.13 (m, 1H), 3.98–3.93 (m, 1H), 3.87–3.81 (m, 1H), 2.42–2.35 (m, 3H), 2.26 (s, 3H), 2.20 (s, 3H), 2.20–2.13 (m, 1H), 2.11 (s, 3H), 1.87– 1.80 (m, 4H), 1.74–1.69 (m, 1H), 0.90 (d, 3JHH = 7Hz, 3H), 0.81 (d, 3JHH = 7Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 200.8 (d, 1JPC = 47 Hz), 169.4 (d, JPC = 9Hz), 143.3 (d, JPC = 14 Hz), 140.1 (d, JPC = 7 Hz), 139.9 (d, JPC = 6 Hz), 137.9, 136.0 (d, JPC = 41 Hz), 128.1, 128.0, 126.9, 126.7, 126.6, 126.4, 72.2, 70.0, 59.3 (d, JPC = 23 Hz), 37.9 (d, JPC = 20 Hz), 37.6 (d, JPC = 20 Hz), 32.6, 24.0, 23.9, 22.6 (d, JPC = 10 Hz), 22.5 (d, JPC = 8 Hz), 21.2, 19.3, 18.1; HRMS calcd for:  95 C27H34PNO: 419.2387; Found: 419.2375; LRMS (EI): m/z [%] 419, 418 [45, 5, M+], 301, 300 [8, 33, M+ − Mes]. Table 3.10 COSY Correlation for Compound 3.22a. C P O N1 23 4 5 6 7 8 9 10 11 12 13 14 15 16 1718 19 21 20 22 23 24 25 26 27  proton no. 1H δ  (ppm)(mult. J(Hz))a,b,c COSY correlation d H3/H5 6.62–6.57 (m) H7e 2.26 (s) H8 2.11 (s) H9e 2.20 (s) H12/H16 6.81–6.77 (m) H13/H15 H13/H15 6.99–6.93 (m) H12/H14/H16 H14 6.99–6.93 (m) H12/H16 H18/H21 2.42–2.35 (m) 2.20–2.13 (m) H18/H21; H19/H20 H19/H20 1.87–1.80 (m) H18/H21 H23 4.19–4.13 (m) H23’/H24 H23’ 3.98–3.93 (m) H23/H24 H24 3.87–3.81 (m) H23/H23’ H25 1.74–1.69 (m) H26/H27 H26e 0.90 (d, 7) H25 H27e 0.81 (d, 7) H25 a Recorded at 400 MHz. b Assignments made based on HMQC, HMBC and COSY data. c H and H’ are assigned arbitrarily. d Only correlations which could be unambiguously assigned are recorded. e Arbitrarily assigned.  96  Table 3.11 NMR Data for Compound 3.22a. C P O N1 23 4 5 6 7 8 9 10 11 12 13 14 15 16 1718 19 21 20 22 23 24 25 26 27  carbon no. 13C (ppm)a (mult. J(Hz)) mult. 1H (ppm) (mult. J(Hz))b,c,d HMBC correlation 1 136.0 (d, 41) Q  H7/H9: 2.26 (s); 2.20 (s); 2e 140.1 (d, 7) Q  H7: 2.26 (s) 3e 128.0 CH H3/H5: 6.62–6.57 (m) H7: 2.26 (s); H8: 2.11 (s) 4 137.9 Q  H8: 2.11 (s) 5e 128.1 CH H3/H5: 6.62–6.57 (m) H9: 2.20 (s); H8: 2.11 (s) 6e 139.9 (d, 6) Q  H9: 2.20 (s) 7e 22.6 (d, 10) CH3 H7: 2.26 (s) 8 21.2 CH3 H8: 2.11 (s) 9e 22.5 (d, 8) CH3 H9: 2.20 (s) 10 200.8 (d, 47) Q  H12/H16: 6.81–6.77 (m) 11 143.3 (d, 14) Q  H13/H15: 6.99–6.93 (m) 12e 126.7 CH H12/H16: 6.81–6.77 (m) H14: 6.99–6.93 (m) 13/15 126.9 CH H13/H15: 6.99–6.93 (m) 14 126.4 CH H14: 6.99–6.93 (m) H12/H16: 6.81–6.77 (m) 16e 126.6 CH H12/H16: 6.81–6.77 (m) H14: 6.99–6.93 (m) 17 59.3 (d, 23) Q  H18/H21: 2.42–2.35 (m) 18e 37.9 (d, 16) CH2 H18/H21: 2.42–2.35 (m) 2.20–2.13 (m) H19/H20: 1.87–1.80 (m) 19e 24.0 CH2 H19/H20: 1.87–1.80 (m) H18/H21: 2.42–2.35 (m) 2.20– 2.13 (m); H19/H20: 1.87–1.80 (m) 20e 23.9 CH2 H19/H20: 1.87–1.80 (m) H18/H21: 2.42–2.35 (m) 2.20– 2.13 (m); H19/H20: 1.87–1.80 (m) 21e 37.6 (d, 20) CH2 H18/H21: 2.42–2.35 (m) 2.20–2.13 (m) H19/H20: 1.87–1.80 (m) 22 169.4 (d, 9) Q  H23: 4.19–4.13 (m); H23’: 3.98–3.93 (m); 3.87–3.81 (m) 23 70.0 CH2 H23: 4.19–4.13 (m); H23’: 3.98–3.93 (m) H25: 1.74–1.69 (m) 24 72.2 CH H24: 3.87–3.81 (m) H25: 1.74–1.69 (m); H26/H27: 0.81 (d, 7); 0.90 (d, 7); H23’: 3.98–3.93 (m) 25 32.6 CH H25: 1.74–1.69 (m) H26/H27: 0.81 (d, 7); 0.90 (d, 7); H23: 4.19–4.13 (m); H23’: 3.98–3.93 (m) 26e 19.3 CH3 H26: 0.90 (d, 7) H27: 0.81 (d, 7); H25: 1.74–1.69 (m) 27e 18.1 CH3 H27: 0.81 (d, 7) H26: 0.90 (d, 7); H25: 1.74–1.69 (m) a Recorded at 100 MHz. bRecorded at 400 MHz. c Assigments are based on HMQC data. d Only correlations which could be unambiguously assigned were recorded.e Arbitrarily assigned.  97 3.5.20 Synthesis of (S)-MesP=C(3,5-(CF3)2C6H4)C(-C4H8-)(CNOCH(i-Pr)CH2) (3.24a) To a solution of MesP(SiMe3)2 (945 mg, 3.15 mmol) in THF (10 mL) was added MeLi in Et2O (1.1 M, 2.8 mL, 3.15mmol). The reaction mixture was heated to 55 ºC for 1–2 h. An aliquot was removed for 31P{1H} NMR analysis of an aliquot removed from the reaction mixture revealed a single resonance (δ = −187) assigned as MesP(SiMe3)Li. The solution was cooled at −78 ºC and treated with a THF (5 ml) solution of 3,5-(CF3)2C6H4COC(-C4H8-)(CNOCH(i- Pr)CH2) (1329 mg, 3.15 mmol). After warming to room temperature, analysis of an aliquot removed from the reaction mixture by 31P{1H} NMR spectroscopy revealed a singlet resonance, which was assigned as a phosphaalkene (δ = 256). The reaction mixture was quenched with Me3SiCl (342 mg, 3.2 mmol), the solvent evaporated in vacuo and the product was extracted into hexanes (3 × 10 ml). The solvent was removed in vacuo and the phosphaalkene (S)-MesP=C-3,5- (CF3)2C6H4C(-C4H8-)(CNOCH(i-Pr)CH2) (3.24a) was an impure yellow oil. 31P{1H} NMR (121 MHz, THF): δ 256. The solvent was removed in vacuo and the phosphaalkene was purified by bulb-to-bulb distillation (0.01 mmHg) to give 3.24a (1.15 g, 67%) as a yellow oil. [α]D18 −56.4 (c 1.6, CH2Cl2). 31P{1H} NMR (121 MHz, CDCl3): δ 254; 1H NMR (400 MHz, CDCl3): δ 7.45–7.40 (m, 1H), 7.24–7.19 (m, 2H), 6.63–6.56 (m, 1H), 6.55–6.51 (m, 1H), 4.23–4.18 (m, 1H), 3.97–3.92 (m, 1H), 3.88–3.78 (m, 1H), 2.48–2.33 (m, 3H), 2.22 (s, 3H), 2.13 (s, 3H), 2.12–2.09 (m, 1H), 2.08 (s, 3H), 1.89–1.80 (m, 4H), 1.67–1.58 (m, 1H), 0.89 (d, 3JHH = 7Hz, 3H), 0.79 (d, 3JHH = 7Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 196.9 (d, 1JPC = 50 Hz), 168.6 (d, JPC = 9 Hz), 144.9 (d, JPC = 14 Hz), 139.8 (d, JPC = 6 Hz), 139.5 (d, JPC = 5 Hz), 138.9, 134.7 (d, JPC = 42 Hz), 130.4 (q, JFC = 33Hz), 128.4, 128.4, 127.1–126.8 (m), 123.4 (q, 1JFC = 272 Hz), 120.0-119.7 (m),  98 72.3, 70.4, 58.8 (d, 2JPC = 21Hz), 37.6 (d, JPC = 15 Hz), 37.3 (d, JPC = 20 Hz), 32.8, 37.3 (d, JPC = 20 Hz), 24.0, 23.9, 22.2 (d, JPC = 9Hz), 22.1 (d, JPC = 8Hz), 21.0, 19.0, 18.1; HRMS calcd for C29H32NOPF6: 555.2126; Found: 555.2127; LRMS (EI): m/z [%] 557, 556, 555 [8, 29, 84, M+], 528, 527, 526 [5, 25, 72, M+ − Et], 513, 512 [5, 15, M+ − i-Pr], 488, 487, 486 [3, 7, 8, M+ − CF3], 437, 436 [7, 29, M+ − Mes], 406, 405, 404 [18, 26, 100, M+ − C9H12P]. Table 3.12 COSY Correlation for Compound 3.24a. C P O N1 3 5 8 9 10 11 13 14 15 17 18 19 21 22 23 25 26 27 F3C CF3 28 29 2 20 4 6 7 12 16 24  proton no. 1H δ  (ppm)(mult. J(Hz))a,b,c COSY correlation d H3e 6.59 (s) H5 H5e 6.53 (s) H3 H7e 2.22 (s) H8 2.08 (s) H9e 2.13 (s) H12/H16 7.20 (m) H14 H14 7.42 (m) H12/H16 H20/H23 2.48–2.33 (m); 2.12–2.09 (m) H20/H23 H21/H22 H21/H22 1.89–1.80 (m) H20/H23 H25 4.23–4.18 (m) H25’; H26 H25’ 3.97–3.92 (m) H25; H26 H26 3.88–3.78 (m) H25; H25’ H27 1.67–1.58 (m) H28/H29 H28e 0.89 (d, 7) H27 H29e 0.79 (d, 7) H27 a Recorded at 400 MHz. b Assignments made based on HMQC, HMBC and COSY data. c H and H’ are assigned arbitrarily. d Only correlations which could be unambiguously assigned are recorded.e Arbitrarily assigned.  99 Table 3.13 NMR Data for Compound 3.24a. C P O N1 3 5 8 9 10 11 13 14 15 17 18 19 21 22 23 25 26 27 F3C CF3 28 29 2 20 4 6 7 12 16 24  carbon no. 13C (ppm)a (mult. J(Hz)) mult. 1H (ppm) (mult. J(Hz))b,c,d HMBC correlation 1 134.7 (d, 42) Q  H3/H5: 6.59 (s); 6.53 (s) 2e 139.8 (d,6) Q  H7: 2.22 (s) 3/5 128.4 CH H3/H5: 6.59 (s): 6.53 H7/H9: 2.22 (s); 2.13 (s); H8: 2.08 (s); H3/H5: 6.59 (s); 6.53 (s) 4 138.9 Q  H8: 2.08 (s) 6e 139.5 (d, 5) Q  H9: 2.13 (s) 7e 22.2(d, 9) CH3 H7: 2.22 (s) H3/H5: 6.59 (s); 6.53 (s) 8 21.0 CH3 H8: 2.08 (s) H3/H5: 6.59 (s); 6.53 (s) 9e 22.1(d, 8) CH3 H9: 2.13 (s) H3/H5: 6.59 (s); 6.53 (s) 10 196.9 (d, 50) Q  H12/H16: 7.20 (m) 11 144.9 (d, 14) Q  H20/H23: 2.48–2.33 (m); 12/16 127.1–126.8 (m) CH H12/H16: 7.20 (m) H12/H16: 7.20 (m); H14: 7.42 (m) 13/15 130.4 (q, 33) Q 14 120.1–119.8 (m)  CH H14: 7.42 (m) H12/H16: 7.20 (m) 17/18 123.4 (q, 272) CF3  H12/H16: 7.20 (m); H14: 7.42 (m) 19 58.8 (d, 21) Q  H21/H22: 1.89–1.80 (m); H20/H23: 2.48–2.33 (m) 20e 37.6 (d,15) CH2 H20/H23: 2.48–2.33 (m); 2.12–2.09 (m) H20/H23: 2.48–2.33 (m); 21e 24.0 CH2 H21/H22: 1.89–1.80 (m) H21/H22: 1.89–1.80 (m); H20/H23: 2.48–2.33 (m); 2.12– 2.09 (m) 22e 23.9 CH2 H21/H22: 1.89–1.80 (m) H21/H22: 1.89–1.80 (m); H20/H23: 2.48–2.33 (m); 2.12– 2.09 (m) 23e 37.3 (d,20) CH2 H20/H23: 2.48–2.33 (m); 2.12–2.09 (m) H20/H23: 2.48–2.33 (m); 24 169.9 (d, 8) Q  H25: 4.23–4.18 (m); H25’: 3.97–3.92 (m); H26: 3.88–3.78 (m) 25 70.4 CH2 H25: 4.23–4.18 (m);  H25’: 3.97–3.92 (m) H27: 1.67–1.58 (m) 26 72.3 CH H26: 3.88–3.78 (m) H28/H29: 0.89 (d, 7); 0.79 (d, 7); H27: 1.67–1.58 (m) 27 32.8 CH H27: 1.67–1.58 (m) H28/H29: 0.89 (d, 7); 0.79 (d, 7); H25/H25’: 4.23–4.18 (m); 3.97– 3.92 (m) 28e 19.0 CH3 H28: 0.89 (d, 7) H29: 0.79 (d, 7); H27: 1.67–1.58 (m) 29e 18.1 CH3 H29: 0.79 (d, 7) H28: 0.89 (d, 7); H27: 1.67–1.58 (m) a Recorded at 100 MHz. bRecorded at 400 MHz. c Assigments are based on HMQC data. d Only correlations which could be unambiguously assigned were recorded. e Arbitrarily assigned.  100 3.5.21 X-ray Crystallography All single crystals were immersed in oil and mounted on a glass fiber. Data were collected on a Bruker X8 APEX diffractometer with graphite- monochromated Mo Kα radiation. All structures were solved by direct methods and subsequent Fourier difference techniques. All non-hydrogen atoms were refined anisotropically with hydrogen atoms being included in calculated positions but not refined. All data sets were corrected Lorentz and polarization effects. All calculations were performed using SHELXTL159 crystallographic software package from Bruker-AXS. Additional crystal data and details of the data collection and structure refinement are given in Table 3.14.  101  Table 3.14 X-ray Data Collection and Refinement Details.a  3.6a and 3.6b 3.9a formula 2 × C31H37N1O1P2 C25H32NOP fw 1003.11 393.49 cryst syst Triclinic Hexagonal space group P1 P61 color Colorless Colorless a (Å) 8.196(1) 8.697(1) b (Å) 10.656(1) 8.697(1) c (Å) 15.571(2) 50.627(8) α (deg) 101.997(9) 90 β (deg) 91.31(1) 90 γ (deg) 96.89(1) 120 V (Å3) 1319.4(3) 3316(6) T (K) 173 173 Z 1 6 µ(Mo Kα) (cm-1) 0.190 0.139 cryst size (mm3) 0.25 × 0.25 × 0.1 0.6 × 0.4 × 0.3 calcd density (Mg m-3) 1.262 1.182 2θ(max) (deg) 56.8 56.4 no. of reflns 21909 55634 no. of unique data 11052 5413 R(int) 0.0422 0.0704 refln/param ratio 17.08 20.82 R1b 0.0431; I > 2σ(I) 0.0471; I > 2σ(I) wR2 (all data)c 0.1174 0.1010 GOF 1.005 1.082 a Adapted with permission from Angew. Chem. Int. Ed., 2008, 47, 8064-8067. © 2008 Wiley- VCH Verlag GmbH & Co. KGaA. b R1 = Σ||Fo|-|Fc|/Σ|Fo|. c wR2(F2[all data]) = {Σ[w(Fo2 – Fc2)2/Σ[w(Fo2)2]}1/2 Data has been removed for copyright reasons. The data described X-ray data for compound 3.9a it is found in Table 1 of the original source’s supporting information. Julien Dugal-Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064- 8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.  102 CHAPTER 4 Group 9 Complexes of Enantiomerically Pure Phosphaalkene–Oxazolines: A Catalyst for Rhodium Catalyzed Allylic Alkylation*  4.1 Introduction In Chapter 3, the synthesis and the properties of enantiomerically pure phosphaalkene- oxazolines (PhAk–Ox) were presented. This chapter discusses the coordination chemistry of PhAk–Ox’s to late transition metals. To gain insight into the coordination chemistry of the PhAk–Ox ligands, metal complexes were generated and characterized using NMR and X-ray crystallography. The isolated PhAk–Ox complexes were then probed for catalytic activity. Due to the novelty of PhAk–Ox ligands, only isolated metal complexes were used to investigate the catalytic potential of these ligands. Our concerns for using complexes generated in situ were that these might lead to inconsistent results, false negatives, and/or false positives. For this reason all the ligands presented in this chapter were purified. A recent paper published by Ozawa and coworkers is discussed because it is relevant to the work described in this chapter. After our initial disclosure of the PhAk–Ox ligands, Ozawa and coworkers reported another chiral phosphaalkene, based on the Josiphos motif (Scheme 4.1).190 In contrast to our synthesis of PhAk–Ox’s, Ozawa and coworkers did not incorporate chiral pool materials into the ligand, but instead used a diastereoselective synthetic approach. The linchpin of their strategy revolved around using a method developed by Kagan utilizing a chiral auxiliary to direct the α-lithiation of ferrocene-derivative 4.1 to one diastereomer.191  * Versions of sections of this chapter have been published or will be published. Julien Dugal- Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. Julien Dugal-Tessier, Gregory R. Dake and Derek P. Gates, to be submitted.  103 Subsequent transformations yielded aldehyde 4.2 with high enantiomeric purity. Phosphaalkenes of type 4.3 were synthesized using a phospha-Peterson reaction of Mes*P(SiMe3)Li with an aldehyde in synthetically useful yields. The use of the bulky Mes* as a P-substituent is usually required to make isolable phosphaalkenes derived from aldehydes. Phosphaalkene 4.3 was mixed with [Pd(C3H5)Cl]2 dimer and upon the later addition of AgOTf palladium allyl complex 4.4 was obtained. Analogously to previously obtained results from the Ozawa and coworkers (Chapter 1.4.5.1), the complex was used in the hydroamination of 1,3-dienes in up to 21% ee (Scheme 4.1). These results became an initial benchmark for comparing catalytic activity. Fe O O OMe Fe CHO PPhR Mes*P(SiMe3)Li Fe C PPhR P H Mes* 4.3 R = Ph, or Naph Fe C P Ph2 P H Mes* Pd OTf 4.4 NHPh 4.4 (5 mol %) 31% yield (21% ee) PhNH2 4.1 4.2 1) t-BuLi 2) PhRPCl 3) p-TsOH•nH2O  Scheme 4.1 Synthesis of 1-Phosphaethenyl-2-phosphanylferrocenes and Its Catalytic Activitity.  In this chapter, the coordination of the PhAk–Ox ligand to Group 9 metals, iridium(I) and rhodium(I), is reported. The PhAk–Ox rhodium complexes were also active in asymmetric allylic alkylation with yields and enantioselectivities that were unprecedented for phosphaalkene ligands at the time.   104 4.2 Results and Discussion 4.2.1 Synthesis of Iridium Complexes Commercially available metal precursors were added to phosphaalkene 3.9a in a NMR tube. Iridium(I) initially gave promising results and was thus investigated in more detail. Mixing of phosphaalkene 3.9a with [IrCl(cod)]2 in dichloromethane generated a chemical species whose spectral properties revealed two resonances, δ = 197 and δ = 190 by 31P{1H} NMR spectroscopy. We speculated that the presence of two signals in the NMR spectrum was due to the chloride counter-ion being found in both the inner- and outer-sphere of the cationic iridium center. These signals converged to a single resonance [δ(31P) = 197] upon the addition of AgOTf, AgBF4 or NaBPh4 as a source of more weakly coordinating anions (Scheme 4.2). The AgCl or NaCl salts were filtered through diatomaceous earth and X-ray quality crystals of [4.5]OTf (72% yield) were obtained by layering the reaction mixture with hexanes. Complex [4.5]OTf was characterized by NMR spectroscopy (Figure 4.1), elemental analysis, and X-ray crystallography (Figure 4.2). [IrCl(cod)]2 NaX or AgX X C O NP Ir C O NP 3.9a [4.5] NaX= NaBPh4, AgX=AgOTf or AgBF4 Scheme 4.2 Iridium Cyclooctadiene Complexes of Ligand 3.9a.   105  Figure 4.1 31P{1H}NMR (121 MHz, THF) Spectrum of [4.5]OTf.  The molecular structure of complex [4.5]OTf is shown in Figure 4.2 and important metrical parameters are given in the figure caption. Refinement and solution details are given in Table 4.4. To the best of our knowledge, previously reported examples of structurally characterized phosphaalkene iridium complexes are limited to a single example of an Ir(III)DPCB complex.192 The P=C bond length decreases upon coordination [1.663(5) Å in [4.5]OTf compared with 1.679(2) Å in 3.9a]. The C–P=C dihedral angle increases upon coordination to iridium [114.3(2)º in [4.5]OTf compared with 105.3(1)º in 3.9a]. The P–Mes bond length also decreases upon coordination to iridium [1.806(5) Å in [4.5]OTf compared with 1.826(2) Å in 3.9a]. The shortening of the P=C and the P–Mes bond lengths as well as the increase of the C–P=C dihedral angle has also been observed with other phosphaalkene complexes, such as in MesP=CPh(2-Py) complexes of palladium(II) and platinum(II) (Chapter 2.2.2). We speculate that these structural changes in bond lengths and bond angles upon coordination are the result of a reorganization at phosphorus closer to the idealized sp2 hybridized geometry. Upon coordination the p character of the lone pair increases, resulting in an  106 increase of the observed C–P=C dihedral angle. Subsequently, the s character of both σ bonds increases, resulting in the observed shortening of the P=C and P–Mes bond. The P=C bond geometry becomes closer to an idealized sp2 hybridization [C–P=C (θ) = 120º] upon coordination. The dihedral angle between the P=C bond and the best plane of the Mes group does not change upon coordination [77.5º in [4.5]OTf compared to 78.6º in 3.9a]. Interestingly, the dihedral angle between the P=C bond and the best plane of the C-aryl group becomes more acute upon coordination [64.8º in [4.5]OTf compared with 80.4º in 3.9a]. This observation could indicate that π conjugation between the C-aryl group and the P=C bond is more important in the complexes than in the proligand. However, crystal-packing effects might play a role in the observed orientation of the C-aryl group.  107    Figure 4.2 Molecular Structure of [4.5]OTf (50% Probability Ellipsoids). All hydrogen atoms and the counter ion (OTf) are omitted for clarity. Selected bond lengths [Å] and angles [deg]: C1–P4 = 1.806(5), C10–P4 = 1.663(5), C10–C11 = 1.490(7), C10–C17 = 1.546(6), C17–C20 = 1.514(7), C20–N1 = 1.290(6), C20–O1 = 1.335(5), N1–Ir1 = 2.077(4), P4– Ir1 = 2.212(1), C26–Ir1 = 2.141(4), C27–Ir1 = 2.134(5), C30–Ir1 = 2.217(5), C31–Ir1 = 2.244(4); C17–C10–P4 = 118.5(4), C11–C10–P4 = 120.9(3), C20–C17–C10 = 111.3(4), N1– C20–O1 = 115.8(5), N1–C20–C17 = 129.4(4), O1–C20–C17 = 114.7(4), C20–N1–Ir1 = 129.1(3), C10–P4–C1 = 114.3(2), C10–P4–Ir1 = 121.0(2), C26–Ir1–P4 = 92.8(1), C27–Ir1–P4 = 95.6(2), N1–Ir1–C30 = 91.7(2), N1–Ir1–C31 = 96.4(2), C24–C23–C25 = 112.8(5). Reproduced with permission from Angew. Chem. Int. Ed., 2008, 47, 8064-8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.  The Ir–P bond length in [4.5]OTf [Ir(1)–P(4) = 2.212(1) Å] is shorter than in other structurally characterized low-valent phosphorus complexes such as phosphinine–iridium(I) complexes [ca. 2.4 Å],193 phosphaferrocene–iridium complexes [av 2.298(2) Å],194 and iridium(III)-DPCB complexes [av 2.53(2) Å].192 The observed Ir–P [Ir(1)–P(4) = 2.212(1) Å] and Ir–N [Ir(1)–N(1) = 2.077(4) Å] bond lengths in [4.5]OTf are shorter than the ones found in the analogous PHOX–Ir(cod) complex [Ir–P = 2.266(3) Å, Ir–N = 2.119(7) Å].195 These   Figure 4.2 has been removed for copyright reasons. The figure depicted the solid state molecular structure of [4.5]OTf with selected metrical parameters and is found as Figure 2 in the original source. Julien Dugal-Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.  108 observations are consistent with stronger electron withdrawing properties of phosphaalkenes compared with phosphines. Iridium complexes are active in a variety of achiral and asymmetric catalytic reactions.196 Interestingly, there is no precedence for phosphaalkene ligands being utilized in any iridium catalyzed reactions. Applying the cod complex [4.5]OTf in preliminary screening reactions such as hydrogenation and allylic alkylation did not yield fruitful results. Further investigation of other iridium PhAk–Ox complexes as well as other iridium catalyzed reactions was not done. Iridium catalyzed reactions with PhAk–Ox ligands is still an area of interest.  4.2.2 Synthesis of Rhodium Complexes Successful coordination of the PhAk–Ox ligand 3.9a to iridium(I) led us to investigate its rhodium(I)-based coordination chemistry. Complex [4.6]OTf was synthesized analogously to the iridium(I) complex [4.5]OTf (Scheme 4.3). Mixing phosphaalkene 3.9a with [RhCl(cod)]2 generated a chemical species whose spectral properties revealed two resonances by 31P{1H} NMR spectroscopy [δ = 229 (1JRhP = 187 Hz) and δ = 217 (1JRhP = 179 Hz)]. We speculated that the presence of two signals in the NMR spectrum was due to the chloride counter-ion being found in both the inner- and outer-sphere of the cationic rhodium center. Exchange of the chloride counterion with trifluoromethanesulfonate by treatment with AgOTf generated a chemical species with a single resonance [δ = 216 (1JRhP = 179 Hz)] (Figure 4.3). X-ray quality crystals of [4.6]OTf (89% yield) were obtained by layering a solution of the complex in CH2Cl2 with hexanes (Figure 4.4).   109 [RhCl(cod)]2 NaX or AgX X C O NP Rh C O NP 3.9a [4.6]X NaX=NaBArF, AgX=AgOTf Scheme 4.3 Rhodium Cyclooctadiene Complexes of Ligands 3.9a.   Figure 4.3 31P{1H} NMR (121 MHz, CDCl3) Spectrum of [4.6]OTf.  The molecular structure of complex [4.6]OTf is shown in Figure 4.4, and important metrical parameters are given in the figure caption. Refinement and solution details are given in Table 4.4. Intriguingly, the metrical parameters of the phosphaalkene ligand moiety are indistinguishable from the one in the iridium complex [4.5]OTf. The P=C [1.664(2) Å] and P–  110 Mes [1.804(2) Å] bond lengths decrease upon coordination when compared to the free ligand 3.9a [P=C = 1.679(2) Å, P–Mes = 1.826(2) Å respectively]. The C–P=C dihedral angle also increases upon coordination with rhodium [113.6(1)º in [4.6]OTf when compared with 105.3(1)º in 3.9a]. These observations are consistent with a similar structural rearrangement in the PhAk– Ox ligand 3.9a upon coordination to both rhodium and iridium. The dihedral angle between the P=C bond and the best plane of the Mes group in [4.6]OTf (77.0º) does not change upon coordination (78.6º in 3.9a), but is more acute than the one found in a [(DPCB)Rh(cod)]BF4 complex [90.04(9)º].128 The orthogonal orientation of the Mes* in the [(DPCB)Rh(cod)]BF4 complex is not surprising due to the large steric bulk of the Mes* compared with the Mes substituent. The dihedral angle between the P=C bond and the best plane of the C-aryl group in [4.6]OTf (64.9º) becomes more acute upon coordination (80.4º in 3.9a). These observations are similar to the ones noted upon coordination to iridium (Chapter 4.2.1).  111   Figure 4.4 Molecular Structure of [4.6]OTf (50% Probability Ellipsoids). All hydrogen atoms and the counter ion (OTf) are omitted for clarity. Selected bond lengths [Å] and angles [º]: C1–P1 = 1.804(2), C10–P1 = 1.664(2), C10–C11 = 1.483(3), C10–C17 = 1.553(3), C17–C20 = 1.523(3), C20–O1 = 1.346(3), C20–N1 = 1.283(3), N1–Rh1 = 2.090(2), P1–Rh1 = 2.2013(5), C26–Rh1 = 2.148(2), C29–Rh1 = 2.285(2), C30–Rh1 = 2.234(2), C33– Rh1 = 2.152(2); C11–C10–P1 = 120.9(2), C17–C10–P1 = 118.8(2), C20–C17–C10 = 110.8(2), N1–C20–O1 = 115.9(2), N1–C20–C17 = 129.6(2), C20–N1–Rh1 = 129.3(1), C10–P1–C1 = 113.6(1), C10–P1–Rh1 = 121.6(1), N1–Rh1–P1 = 92.84(6), C26–Rh1–P1 = 92.84(6), C33–Rh1– P1 = 95.20(6), N1–Rh1–C29 = 96.95(7), N1–Rh1–C30 = 92.10(7), C24–C23–C25 = 111.4(2).  Phosphaalkenes and other low-valent phosphorus rhodium(I) complexes have also been structurally characterized offering a useful comparison of the coordination chemistry of the PhAk–Ox ligand. The Rh–P bond length in [4.6]OTf [Rh(1)–P(1) = 2.2013(2) Å] is shorter than those of Rh(I) complexes of DPCB and Mes*P=C–(2-Py)–C=PMes* [ca. 2.23 Å],127,128 and are shorter than the ones typically found for phosphines [ca. 2.27 Å].197 Presumably, this reflects the donor/acceptor properties of phosphaalkenes. The Rh–N bond length in [4.6]OTf [Rh(1)–N(1) = 2.090(2) Å] is longer than the one in [Mes*P=C–(2-py)–C=PMes*]RhCl [2.053(3) Å],127 but shorter than those of phosphine–oxazolines [ca. 2.11 Å].198 These observations reinforce the better accepting properties of phosphaalkene-ligands compared to phosphines.  112  4.2.3 Catalytic Activity of Rhodium Complexes Rhodium complexes have been used in a variety of different asymmetric catalytic reactions.199 Studies towards the use of rhodium in metal catalyzed allylic alkylation have not been investigated to the extent of other metals such as palladium, molybdenum, and iridium.132,200 Preliminary studies of the complex [4.6]OTf in rhodium catalyzed allylic alkylation revealed encouraging results. Under certain allylic alkylation conditions, rhodium has a unique property that the nucleophile adds preferentially to the same position as the leaving group (Figure 4.5).199 For example, branched allyl acetates will give branched malonate products. These observations are consistent with rhodium catalyzed allylic alkylation proceeding with a σ-allyl intermediate (III) and not a π-allyl intermediate. Mechanistically, rhodium catalyzed allylic alkylation can be rationalized as two SN2’ reactions: the first during the ionization step (II →III) and the second during the nucleophilic addition step (III→IV).199,201 We were interested in investigating rhodium catalyzed allylic alkylation because electron withdrawing ligands are commonly used. In addition, the number of examples of enantioselective rhodium catalyzed allylic alkylation is limited.202-204  113 LnRh I X X LnRh I LnRh III Nu Nu LnRh I Nu –X– complexation ionizationnucleophilic addition R R RR R R R I III IIIV Ln RhIII RhIIILn  Figure 4.5 Postulated Mechanism of Rhodium Catalyzed Allylic Alkylation.  Rhodium catalyzed allylic alkylation was tested with 1-phenylallyl acetate, dimethyl malonate and NaH in THF to give 46% yield in 11% ee. The experiments presented in Scheme 4.4 are key results of the optimization studies performed in order to increase yields and enantioselectivities. Different solvents were screened such as toluene, tetrahydrofuran and dichloromethane by using NaH as the base. The highest enantioselectivities were obtained with dichloromethane as a solvent, although still in low yield and enantioselectivities (Scheme 4.4, entry 1). Solvents were not re-investigated again and CH2Cl2 was used for all future reactions. Different bases were investigated and Cs2CO3 gave better yields with similar enantioselectivities (Scheme 4.4, entry 2). In order to accelerate the ionization step, the acetate group was replaced with a carbonate leaving group. Higher yields were obtained with the carbonate leaving group with similar enantioselectivities (Scheme 4.4, entry 3). Generating [4.6]OTf in situ resulted in lower yields and enantioselectivities. The nature of the metal counter ion such as using [4.6]BArF  114 had no noticeable effect on the enantioselectivities. These results were encouraging since they served as a useful starting point for further studies and that low enantioselectivities were better than zero. X 5 mol % [4.6]OTf CH2(CO2Me)2 base, CH2Cl2 20 ºC, 16 h CH(CO2Me)2 (1)  X = OAc,            base = NaH (2)  X = OAc,            base = Cs2CO3 (3)  X = OCO2Et,      base = Cs2CO3 30% (22% ee) CO 2 47% (26% ee)  CO 2 77% (20% ee)  CO2 X C O NP Rh [4.6]X Scheme 4.4 Rhodium Catalyzed Allylic Alkylation Using Rhodium Complex [4.6]OTf.  The screening of solvents and bases yielded no major increases in enantioselectivities. At this point, modification of the ligand framework was also investigated as a means of improving catalytic performance. A more electron rich PhAk–Ox ligand might accelerate the ionization step by making the metal more electron rich. Complex [4.7]OTf [δ(31P) = 216 (1JRhP = 180 Hz)] with a para-methoxy group at the C-aryl substituents was synthesized from 3.23a (87%) (Scheme 4.5). Unfortunately, complex [4.7]OTf did not improve yields or enantioselectivities. OCO2Et 5 mol % [4.7]OTf CH2(CO2Me)2 Cs2CO3, CH2Cl2 20 ºC, 16 h CH(CO2Me)2  63% (17% ee) [RhCl(cod)]2 AgOTf –OTf C O NP Rh C O NP MeO MeO 3.14a [4.7]X  Scheme 4.5 Synthesis of [4.7]OTf and its Activity in Allylic Alkylation.   115 At this point, we speculated that the P-Mes group might have too much local symmetry around the phosphorus to obtain high enantioselectivities. A depiction of the ligand roughly depicts the coordination of the PhAk–Ox ligand bound to rhodium (Figure 4.6). We suspected that the two methyl substituents at the 2,6 positions of the P-Mes group project the same steric bulk in the two quadrants around the phosphorus atom. We hypothesized that a ligand with only one substituted ortho position would sterically differentiate the two quadrants around the phosphorus atoms. Rh Rh small large medium medium large medium small small N Rh P C O R R H N Rh P C O R H L S M M  Figure 4.6 Pictographic Representation of PhAk–Ox Ligands Coordinated to Rhodium.  Thus, complexes [4.8]OTf [δ(31P) = 219 (1JRhP = 180 Hz)] and [4.9]OTf [δ(31P) = 227 (1JRhP = 181 Hz)] were synthesized from 3.9c (46% yield) and 3.9d (68% yield) respectively (Scheme 4.6). The use of complex [4.8]OTf in allylic alkylation resulted in similar yields and an increase in enantioselectivities (Scheme 4.6, entry 1). Surprisingly, increasing the bulk of the 2- position of the P-aryl group with a tert-butyl group ([4.9]OTf) had little effect on the yields but was detrimental to the enantioselectivities (Scheme 4.6, entry 2).  116 [RhCl(cod)]2 AgX X C O NP R Rh C O NP R 3.9c R = i-Pr 3.9d R = t-Bu [4.8]X R = i-Pr [4.9]X R = t-Bu X = OTf or BF4 OCO2Et 5 mol % [X]OTf CH2(CO2Me)2 Cs2CO3, CH2Cl2 20 ºC, 16 h CH(CO2Me)2 (1)  X =  4.8  75% (33% ee) (2)  X =  4.9  73% (10% ee) Scheme 4.6 Rhodium Complexes of Phosphaalkene Ligand 3.9c and 3.9d.  Due to the unique substitution pattern of the mono-ortho substituted P-aryl group a solid state molecular structure was important. I was unable to obtain X-ray quality crystals of [4.8]OTf but [4.8]BF4 was successfully structurally characterized (Figure 4.7). Interestingly, the 2-i-Pr group of the P-aryl substituent was on the same side as the oxazoline i-Pr group in the solid state molecular structure of [4.8]BF4. This result was unexpected since steric interactions between both i-Pr groups were anticipated. This brief study calls for a deeper investigation of the structure-conformation effects. The P=C bond length in [4.8]BF4 [1.665(5) Å] is similar to the ones observed for the iridium [1.663(5) Å] and the rhodium [1.664(2) Å] complexes [4.5]OTf and [4.6]OTf respectively. The dihedral angles between the P=C bond and the best plane of P- aryl group, and the best plane of the C-phenyl group are 83.6º and 76.6º respectively. Both of these dihedral angles are greater than the ones found in the rhodium complex [4.6]OTf [77.0º and 64.9º respectively].  117  Figure 4.7 Molecular Structure of [4.8]BF4 (25% Probability Ellipsoids). All hydrogen atoms and the counter ion (BF4) are omitted for clarity. Selected bond lengths [Å] and bond angles [º]: C1–P1 = 1.819(6), C10–P1 = 1.665(5), C10–C17 = 1.564(7), C10–C11 = 1.461(8), C17–C20 = 1.517(7), C20–O1 = 1.341(6), C20–N1 = 1.267(7), N1–Rh1 = 2.087(5), P1–Rh1 = 2.234(2), C26–Rh1 = 2.222(7), C29–Rh1 = 2.130, C30–Rh1 = 2.105(7), C33–Rh1 = 2.264(7); C17–C10–P1 = 116.4(4), C11–C10–P1 = 123.6(4), C20–C17–C10 = 107.8(4), N1– C20–O1 = 117.4(5), N1–C20–C17 = 126.1(5), O1–C20–C17 = 116.4(5), C20–N1–Rh1 = 126.8(4), C10–P1–C1 = 112.2(3), C10–P1–Rh1 = 117.3(2), N1–Rh1–P1 = 84.9(1), N1–Rh1– C26 = 92.6(3), N1–Rh1–C33 = 95.1(3), C29–Rh1–P1 = 95.5(3), C30–Rh1–P1 = 93.5(3), C24– C23–C25 = 117.5(7).  The Rh–P bond length found in [4.8]BF4 [Rh(1)–P(1) = 2.234(2) Å] is longer than the one found in complex [4.6]OTf [2.2013(5) Å], and similar to the ones found in DPCB and Mes*P=C–(2-Py)–C=PMes* [ca. 2.23 Å].127,128 The Rh–N bond length in [4.8]BF4 [2.087(5) Å] is similar to the one found in [4.6]OTf [2.090(2) Å]. We suspect that the longer Rh–P bond length in [4.8]BF4 is due to steric interactions between the 2-i-Pr of the P-aryl group and the rhodium cod ligand. The similar Rh–N bond length indicate similar electronic properties between [4.8]BF4 and [4.6]OTf. During the process of ligand optimization, we performed experiments to ascertain the mechanism of allylic alkylation in more detail. With electron withdrawing ligands, examples of  118 stereospecific rhodium catalyzed allylic alkylation have been reported.201,205-211 A stereospecific pathway is possible if the equilibration of the σ-allyl intermediate is slow and nucleophilic addition is fast (Figure 4.8).199 If this pathway is in effect, obtaining both high enantioselectivities and complete conversion of the allyl carbonate is unfeasible. LnRh III R R R Ln RhIII Ln RhIII slow slow R OLG R OLG RhI RhI Nu Nu fast fast Nu Nu  Figure 4.8 Postulated Mechanism of Stereospecific Pathway of Rhodium Catalyzed Allylic Alkylation.212  Investigation of the enantioselectivities as a function of yields with a N,O- bis(trimethylsilyl)acetamide (BSA)/ potassium acetate (KOAc) system revealed that the enantioselectivities are constant at the beginning and decrease at higher conversions (Scheme 4.7, entry 1-3). Importantly, the allyl carbonate isolated from the reaction mixture had enantiomeric excess, which led us to deduce that a kinetic resolution was taking place. The addition of halide sources to try and induce a faster equilibration of the σ-allyl intermediate was unsuccessful.213,214 During the course of these studies the first report of a rhodium catalyzed kinetic resolution of allyl carbonates was published.215 We decided not to investigate rhodium catalyzed allylic alkylation in more detail, as we believed that we could optimize the ligand structure to obtain high enantioselectivities. We focused our attention instead on screening alternative reactions.   119 OCO2Et 5 mol % [4.6]OTf CH2(CO2Me)2 BSA/KOAc, CH2Cl2 CH(CO2Me)2 (1)  17% (65% ee,16 h) (2)  37% (66% ee, 40 h) (3)  66% (47% ee, 72 h) Scheme 4.7 Kinetic Resolution of Allyl Carbonates Using [4.6]OTf.  4.2.4 Spectroscopic Data of Rhodium and Iridium Complexes A small set of rhodium PhAk–Ox complexes was generated in the process of investigating the rhodium catalyzed allylic alkylation. This allowed us to qualitatively probe the effect of rhodium and iridium complexation. Table 4.1 shows the NMR spectral properties of the P=C bond in the free ligand and the ligand after coordination. An upfield shift is observed in both the 31P{1H} NMR and the 13C{1H} NMR spectra when the phosphaalkene ligand coordinates to iridium or rhodium. A similar 31P{1H} NMR chemical shift (ca. Δδ(31P) = −28) is observed for all the PhAk–Ox ligands upon coordination to rhodium. Furthermore, the value of Rh-P scalar coupling is similar for all the rhodium complexes varying between 179-181 Hz. These observations indicate that all the PhAk–Ox ligands bind similarly to rhodium and that they undergo similar structural rearrangement upon coordination. A similar upfield shift is also observed upon rhodium coordination to a DPCB ligand [∆δ(31P) = −18].127,128 No change in the NMR spectra was observed between complex [4.6]OTf (Table 4.1, entry 2) and the more electron donating C-aryl (R1 = 4-MeOC6H4-) complex [4.7]OTf (Table 4.1, entry 4). A downfield 31P{1H} NMR shift [∆δ(31P) = −7] was observed in DPCB⋅PtMe2 complexes upon introduction of a para-methoxy group.99 This suggests that there is minimal to no conjugation between the P=C bond and the C-aryl group in the rhodium complexes as observed for the proligands (see, Chapter 3).  120 Table 4.1 31P{1H} and 13C{1H} NMR Shifts of Rhodium and Iridium Complexes. X R1 C O NP Ar M [4.5]  M = Ir, Ar = Mes, R1 = Ph [4.6]  M = Rh, Ar = Mes, R1 = Ph [4.7]  M = Rh, Ar = Mes, R1 = 4-MeOC6H4 [4.8]  M = Rh, Ar = 2-i-PrC6H4, R 1 = Ph [4.9]  M = Rh, Ar = 2-t-BuC6H4, R 1 = Ph  31P{1H} NMR δ (1JRhP) 13C{1H} NMR δ (1JPC) of P=C entry proligand/complex proligand ligand ∆δa proligand ligand 1 3.9a/[4.5]OTf 244 197 −47 203.3 (48) 175.5 (58) 2 3.9a/[4.6]OTf 244 216 (179) −28 203.3 (48) 180.8 (46) 3 3.9a/[4.6]BArf 244 217 (180) −27 203.3 (48) 4 3.23a/[4.7]OTf 245 216 (180) −29 203.2 (47) 181.1 (45) 5 3.9c/[4.8]OTf 245 219 (180) −26 204.9 (49) 6 3.9c/[4.8]BF4 245 218 (181) −27 204.9 (49) 182.2 (44) 7 3.9d/[4.9]OTf 254 227 (181) −27 196.7 (50) 8 3.9d/[4.9]BF4 254 227 (181) −27 196.7 (50) a ∆δ is the change in the 31P{1H} NMR upon coordination ( i.e. entry 1: ∆δ = 197 − 244 = −47)  Even though the solid state molecular structures for the iridium complex [4.5]OTf and rhodium complex [4.6]OTf are similar, their NMR spectra differ. The 31P{1H} and 13C{1H} NMR spectra of the P=C bond atoms of the iridium complex [4.5]OTf (Table 4.1, entry 1) reveal upfield chemical shifts compared with the ones observed for rhodium complex [4.6]OTf (Table 4.1, entry 2). We speculate that this upfield shift is a consequence of the different donor/acceptor properties of iridium and rhodium. A similar effect was observed in the 31P{1H} NMR between palladium(II) [δ(31P) = 230] and platinum(II) [δ(31P) = 206] complexes of MesP=CPh(2-Py) (Chapter 2).  121 An increase in the value of P–C scalar coupling constant of the P=C bond is observed by 13C{1H} NMR spectroscopy upon coordination of 3.9a to iridium complex (Table 4.1, entry 1). This observation is consistent with an increase in s character of the σ component of the P=C bond upon coordination. A similar increase in the value of the P–C scalar coupling constant of the P=C bond is also observed in other related phosphaalkenes upon complexation [(1JPC = 52 Hz) for MesP=CPh(2-py)·PdCl2 compared with (1JPC = 40 Hz) for MesP=CPh(2-py)]. The value of the P-C scaler coupling constant of the P=C bond is slightly smaller in the rhodium complexes than the proligands (Table 4.1, entry 2,4 and 6). This is presumably due to the coordination of phosphorus to the spin active rhodium. The NMR data is consistent with the X-ray crystallography data and indicate that a change in hybridization occurs at phosphorus upon coordination of the PhAk–Ox ligands.  4.3 Conclusion  In summary, phosphaalkene–oxazolines coordinated to rhodium and iridium were synthesized and their properties discussed. Analysis by both X-ray crystallography and NMR spectroscopy were performed on representative complexes. The data indicate that the phosphorus atom in phosphaalkene–oxazolines undergoes a structural rearrangement closer to an idealized sp2 hybridized geometry. The shorter P–metal bonds in phosphaalkene-oxazoline (P-sp2) complexes indicate that these ligands are more electron withdrawing than analogous phosphine ligands (P-sp3). Coordination of the PhAk–Ox ligand does not increase π-conjugation between the C-aryl group and the P=C bond. Similarly to the proligand, π-conjugation between the C-aryl substituent and the P=C bond is minimal in the metal complexes. The rhodium PhAk–Ox complexes are active in allylic alkylation of 1-phenylallyl acetate with dimethyl malonate  122 generating moderate yields and enantioselectivities. Further investigation found that the rhodium catalyzed allylic alkylation using PhAk–Ox complexes was likely undergoing a stereospecific pathway and this resulted in the kinetic resolution of branched allyl carbonates. These results provide evidence that the PhAk–Ox ligands have the potential to generate high enantioselectivities in asymmetric transformations. Furthermore, allylic alkylation and enantioselectivities and that these ligands can be used in asymmetric catalysis.  4.4 Experimental Section 4.4.1 General Procedures All manipulations of air- and/or water- sensitive compounds were performed under a nitrogen atmosphere using standard Schlenk or glovebox techniques. Hexanes, dichloromethane (CH2Cl2) and toluene were deoxygenated with nitrogen and dried by passing through a column containing activated alumina. Tetrahydrofuran (THF) was dried over sodium and benzophenone. Metal precursors [IrCl(cod)]2, [RhCl(cod)]2, silver tetrafluoroborate (AgBF4) and sodium tetraphenylborate (NaBPh4) were purchased from Strem and used as received. Silver trifluoromethanesulfonate (AgOTf), sodium hydride (NaH), cesium carbonate (Cs2CO3), N,O- bis(trimethylsilyl)acetamide (BSA) and potassium acetate (KOAc) were purchased from Aldrich and used as received. Sodium BArF was purchased from Matrix Scientific and used as received. 1-Phenylallyl acetate and ethyl (1-phenylallyl) carbonate were prepared according to literature precedent.216-218 Phosphaalkenes were prepared according to previous work. 1H, 31P{1H}, 13C{1H} NMR spectra were recorded at 25 ºC on Bruker Avance 300 or 400 MHz spectrometers. 85% H3PO4 was used as an external standard (δ = 0.0 for 31P). 1H NMR spectra were referenced to residual protonated solvent and 13C{1H} NMR were referenced to the deuterated solvent.  123 Elemental analyses were performed in the University of British Columbia Chemistry Microanalysis Facility. Mass spectra were recorded on a Kratos MS 50 instrument in EI mode (70 eV).  4.4.2 Synthesis of MesP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Ir(C8H12)•OTf ([4.5]OTf) Phosphaalkene MesP=CPhC(Me)2(CNOCH(i-Pr)CH2) (115mg, 0.29 mmol), [(cod)IrCl]2 (105 mg, 0.16 mmol) and AgOTf (86 mg, 0.33 mmol) were dissolved in CH2Cl2 (3.0 ml) and stirred for 30 minutes. The reaction mixture was filtered through diatomaceous earth. Cooling of the reaction mixture to −30 ºC with slow addition of hexanes (1 ml) gave red crystals (X-ray quality). The mother liquor was decanted, and the crystals were washed with hexanes (2 × 3 mL) and dried in vacuo for 16 h to give [4.5]OTf (175 mg, 72%) as red crystals. 31P{1H} NMR (121 MHz, CH2Cl2): δ 197; 1H NMR (400 MHz, CDCl3): δ 7.27–7.00 (m, 4H), 6.84 (br s, 1H), 6.64 (br s, 1H), 6.56 (br s, 1H), 6.18 (br s, 1H), 5.25–5.16 (m, 1H), 4.93– 4.87 (m, 1H), 4.58–4.49 (m, 2H), 3.27–3.16 (m, 2H), 2.72–2.61 (m, 1H), 2.61–2.53 (m, 1H), 2.56 (s, 3H), 2.50–2.41 (m, 1H), 2.40–2.34 (m, 1H), 2.33–2.28 (m, 1H), 2.27–2.20 (m, 1H), 2.26 (s, 3H), 2.25 (s, 3H), 2.20–2.08 (m, 1H), 2.19 (s, 3H), 1.97–1.83 (m, 1H), 1.74–1.62 (m, 1H), 1.23 (s, 3H), 1.06 (d, 3JHH=7 Hz, 3H), 0.96 (d, 3JHH = 7Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 176.9 (d, 3JPC = 12 Hz), 175.5 (d, 1JPC = 58 Hz), 142.7 (d, JPC = 2 Hz), 141.5 (d, JPC = 8 Hz), 140.6 (d, JPC = 3Hz), 138.9 (d, JPC = 9 Hz), 129.0 (d, JPC = 6 Hz), 128.9 (d, JPC = 5 Hz), 128.6, 128.3, 128.0, 127.9, 125.3 (d, JPC = 14 Hz), 123.1 (d, 1JPC = 42 Hz), 121.0 (q, 1JFC = 322 Hz), 102.5 (d, 2JPC = 10 Hz), 98.4 (d, 2JPC = 15 Hz), 71.1, 70.6, 67.2, 61.0, 48.8 (d, JPC = 8 Hz), 37.7 (d, JPC = 16 Hz), 36.3 (d, JPC = 5 Hz), 34.1, 33.2, 29.3, 27.1, 25.2 (d, JPC = 8 Hz), 23.1 (d, JPC  Paragraph has been removed for copyright reasons. The paragraph describes the experimental procedure for [4.5]OTf found in the 10th paragraph of the original source’s supporting information. Julien Dugal-Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.  124 = 9 Hz), 22.7 (d, JPC = 5 Hz), 21.4, 18.4, 14.7; anal. calcd for C35H46Cl2F3Ir NO4PSIr: C, 45.30; H, 5.00; N, 1.51; Found: C, 45.24; H, 4.92; N,1.50. Table 4.2 COSY Correlation for Compound [4.5]OTf 1 23 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 20 22 2324 25 C P O N Ir OTf 27 28 30 33 3426 29  proton no. 1H δ  (ppm)(mult. J(Hz))a,b,c COSY correlation d H3e 6.84 (br s) H5 H5e 6.64 (br s) H3 H7e 2.56 (s) H8 2.19 (s) H9e 2.25 (s) H12e 6.56 (br s) H13 H13e 7.01–6.98 (m) H13/H14 H14 7.21–7.18 (m) H15 H15e 7.26–7.24 (m) H14/H16 H16e 7.15–7.10 (m) H15 H18e 2.26 (s) H19e 1.23 (s) H21 4.93–4.87 (m) H21’/H22 H21’ 4.58–4.49 (m) H21/H22 H22 4.58–4.49 (m) H21/H22 H23 2.33–2.28 (m) H24/H25 H24e 1.06 (d, 7) H23 H25e 0.96 (d, 7) H23 H26e 3.27–3.16 (m) H27e 3.27–3.16 (m) H28e 2.50–2.41; 2.40–2.34 H29e 2.27–2.20; 1.97–1.93 H30e 6.18 (br s) H30 H31e 5.25–5.16 (m) H31 H32e 2.72–2.61; 2.61–2.53 H33e 2.20–2.08; 1.74–1.62 a Recorded at 400 MHz. b Assignments made based on HMQC, HMBC and COSY data. c H and H’ are assigned arbitrarily. d Only correlations which could be unambiguously assigned are recorded. e Arbitrarily assigned.      125 Table 4.3 NMR Data for Compound [4.5]OTf. carbon no. 13C (ppm)a (mult. J(Hz)) mult. 1H (ppm)(mult. J(Hz))b,c,d HMBC correlation 1 123.1 (d, 42) Q  H7/H9: 2.56 (s); 2.25 (s); H3/H5: 6.84 (br s); 6.64 (br s) 2 141.5 (d, 8) Q  H7: 2.56 (s) 3e 129.0 (d, 6) CH H3: 6.84 (br s) H8: 2.19 (s); H7: 2.56 (s) 4 142.7 (d, 2) Q  H8: 2.19 (s) 5e 128.9 (d, 5) CH H5: 6.64 (br s) H8: 2.19 (s); H9: 2.25 (s) 6e 140.6 (d, 3) Q  H9: 2.25 (s) 7e 23.1 (d, 9) CH3 H7 2.56 (s) H3: 6.84 (br s) 8 21.4 CH3 H8: 2.19 (s) H3/H5: 6.84 (br s); 6.64 (br s) 9e 22.7 (d, 5) CH3 H9: 2.25 (s) H5: 6.64 (br s) 10 175.5 (d, 58) Q  H18/H19: 1.23 (s); 2.26 (s) 11 138.9 (d, 9) Q  H13/H15: 7.26–7.24; 7.01–6.98 12e 128.0 CH H12: 6.56 (br s) H16: 7.15–7.10 13e 128.3 CH H13: 7.01–6.98 (m) H15: 7.26–7.24 14 125.3 (d, 14) CH H14: 7.21–7.18 (m) H12/H16: 6.56 (br s); 7.15–7.10 15e 127.9 CH H15: 7.26–7.24 (m) H13: 7.01–6.98 16e 128.6 CH H16: 7.15–7.10 (m) H12: 6.56 (br s) 17 48.8 (d, 8) Q  H18/H19: 1.23 (s); 2.26 (s) 18e 37.7 (d, 16) CH3 H18: 2.26 (s) H19: 1.23 (s) 19e 25.2 (d, 8) CH3 H19: 1.23 (s) H18: 2.26 (s) 20 176.9 (d, 12) Q  H18/H19: 1.23 (s); 2.26 (s); H22/H21’: 4.58–4.49 (m) 21 70.6 CH2 H21: 4.93–4.87 (m) H21’: 4.58–4.49 (m) 22 71.1 CH H22: 4.58–4.49 (m) H24/H25: 0.96 (d, 7); 1.06 (d, 7); H21: 4.93–4.87 (m) 23 33.2 CH H23: 2.33–2.28 (m) H24/H25: 0.96 (d, 7); 1.06 (d, 7); H21: 4.93–4.87 (m); H21’: 4.58–4.49 (m) 24e 18.1 CH3 H24: 1.06 (d, 7) H24: 0.96 (d, 7) 25e 14.7 CH3 H25: 0.96 (d, 7) H25: 1.06 (d, 7) 26e 61.0 CH H26/H27: 3.27–3.16 H33:1.74–1.62; H32: 2.72–2.61; 27e 67.2 CH H26/H27: 3.27–3.16  H33: 2.20–2.08; 1.74–1.62; H28: 2.50–2.41 28e 36.3 (d, 5) CH2 H28; 2.50–2.41; 2.40–2.34 H29: 2.27–2.20; 1.97–1.93 29e 27.1 CH2 H29: 2.27–2.20; 1.97–1.93 H30/H31: 6.18 (br s); 5.25–5.16 (m); H28: 2.50–2.41 30e 98.4 (d, 15) CH H30/H31: 5.25–5.16 (m) H29: 2.27–2.20; 1.97–1.93 31e 102.5 (d, 10) CH H30/H31: 6.18 (br s) H29: 1.97–1.93; 2.27–2.20; H32: 2.72–2.61; 2.61–2.53 32e 34.1 CH2 H32: 2.72–2.61; 2.61–2.53 H30/H31: 5.25–5.16 (m); 6.18 (br s); H26/H27: 3.27– 3.16 33e 29.3 CH2 H33: 2.20–2.08; 1.74–1.62 H31: 6.18 (br s); H26/H27 3.27–3.16; H32: 2.72–2.61; 2.61–2.53; 34 121 (q, 322) CF3 a Recorded at 100 MHz. bRecorded at 400 MHz. c Assigments are based on HMQC data. d Only correlations which could be unambiguously assigned were recorded.e Arbitrarily assigned.  126 4.4.3 Synthesis of [MesP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Ir(C8H12)•X ([4.5]X) Crude [4.5]BF4 was synthesized analogously to [4.5]OTf but AgBF4 was added instead of AgOTf. 31P{1H} NMR (162 MHz, CH2Cl2): δ 197. Crude [4.5]BPh4 was synthesized analogously to [4.5]OTf but NaBPh4 was added instead of AgOTf. 31P{1H} NMR (121 MHz, CH2Cl2): δ 197.  4.4.4 Synthesis of [MesP=CPhC(Me)2(CONCH(i-Pr)CH2)]Rh(C8H12)•OTf ([4.6]OTf) To a solution of MesP=CPhCMe2(CONCH(i-Pr)CH2) (135 mg, 0.45 mmol) and [RhCl(cod)]2 (102 mg, 0.21 mmol) in CH2Cl2 (1.5 mL) was added AgOTf (107 mg, 0.42 mmol) and stirred for 5 min. The solution was filtered through diatomaceous earth. Cooling of the reaction mixture to −30 ºC with slow addition of hexanes (3 mL) gave X-ray quality crystals overnight. The mother liquor was decanted, and the crystals were washed with hexanes (3 × 2 mL) and dried in vacuo to give [4.6]OTf (281 mg, 89%) as orange crystals. 31P{1H} NMR (CDCl3, 121 MHz): δ 216 (d, 1JRhP = 179 Hz); 1H NMR (CDCl3, 400 MHz): δ 7.27–7.22 (m, 1H), 7.17–7.10 (m, 2H), 7.01–6.95 (m, 1H), 6.84–6.81 (br s, 1H), 6.62– 6.59 (br s, 1H), 6.53–5.48 (m, 1H), 6.22–6.15 (m, 1H), 5.44–5.35 (m, 1H), 4.81–4.75 (m, 1H), 4.48–4.43 (m, 1H), 4.29–4.23 (m, 1H), 3.60–3.53 (m, 1H), 2.86–2.74 (m, 1H), 2.68–2.54 (m, 2H), 2.56 (s, 3H), 2.53–2.43 (m, 1H), 2.38–2.32 (m, 1H), 2.35 (s, 3H), 2.28–2.21 (m, 2H), 2.22 (s, 3H), 2.16 (s, 3H), 2.13–1.96 (m, 1H), 1.20 (s, 3H), 1.07 (d, 3JHH = 7 Hz, 3H), 1.00 (d, 3JHH = 7 Hz, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 180.8 (d, 1JPC = 46 Hz), 176.4 (d, 3JPC = 14 Hz), 142.5, 141.4 (d, JPC = 9 Hz), 140.2, 139.2 (d, JPC = 10 Hz), 129.1 (d, JPC = 8 Hz), 129.0 (d, JPC = 7 Hz), 128.5, 128.4, 128.4, 127.9, 125.4 (d, JPC = 14 Hz), 124.3 (dd, 1JPC = 28 Hz, 2JRhC = 5 Hz),  127 121.0 (q, 1JFC = 319 Hz), 110.9 (dd, 2JPC = 8 Hz, 1JRhC = 7 Hz), 106.3 (dd, 2JPC = 12 Hz, 1JRhC = 7 Hz), 81.9 (d, 1JRhC = 11 Hz), 76.0 (d, 1JRhC = 11 Hz), 71.0, 70.1, 48.0 (d, 2JPC = 10 Hz), 38.9 (d, JPC = 16 Hz), 35.4 (d, JPC = 4 Hz), 33.0, 32.1, 29.2, 26.7, 24.9 (d, JPC = 7 Hz), 23.3 (d, JPC = 10 Hz), 22.6 (d, JPC = 4 Hz), 21.4, 18.5, 15.1; anal. calcd for C34H44NO4PRhSF3: C, 54.18; H, 5.88; N, 1.86; Found: C, 53.99; H, 5.82; N, 1.85.  4.4.5 Synthesis of [MesP=CPhC(Me)2(CONCH(i-Pr)CH2)]Rh(C8H12)•BArF ([4.6]BArF) To a solution of MesP=CPhC(Me)2(CONCH(i-Pr)CH2) (17 mg, 0.056 mmol) and [RhCl(cod)]2 (14 mg, 0.028 mmol) in CH2Cl2 (1.0 mL) was added NaBArF (50 mg, 0.056 mmol) and stirred for 1 h. The solution was filtered through diatomaceous earth. The solvent was slowly evaporated to give orange crystals. The crystals were washed with hexanes (3 × 1 mL) and dried in vacuo to give [4.6]BArF (50 mg, 61%) as orange crystals. 31P{1H} NMR (121 MHz, CDCl3): δ 217 (d, 1JRhP = 180 Hz); 1H NMR (300 MHz, CDCl3): δ 7.77–7.70 (m, 8H), 7.57–7.53 (m, 1H), 7.27–7.21 (m, 1H), 7.18–7.06 (m, 2H), 7.03– 6.95 (m, 1H), 6.83–6.80 (m, 1H), 6.62–6.58 (m, 1H), 6.53–6.47 (m, 1H), 5.65–5.56 (m, 1H), 5.27–5.15 (m, 1H), 4.53–4.46 (m, 1H), 4.35–4.28 (m, 1H), 3.93–3.85 (m, 1H), 3.79–3.68 (m 1H), 3.68–3.60 (m, 1H), 2.71–2.45 (m, 3H), 2.53 (s, 3H), 2.39–2.30 (m, 1H), 2.27–2.15 (m, 2H), 2.24 (s, 3H), 2.20 (s, 3H), 2.14 (s, 3H), 2.11–1.90 (m, 3H), 1.19 (s, 3H), 1.00 (d, 3JHH = 7 Hz, 3H), 0.96 (d, 3JHH = 7 Hz, 3H).   128 4.4.6 Synthesis of [MesP=C(4-OMeC6H4)C(Me)2(CNOCH(i- Pr)CH2)]Rh(C8H12)•OTf ([4.7]OTf) To a solution of MesP=C(4-OMeC6H4)C(Me)2(CNOCH(i-Pr)CH2) (106 mg, 0.25 mmol) and [RhCl(cod)]2 (49 mg, 0.099 mmol) in CH2Cl2 (1 mL) was added AgOTf (54 mg, 0.21 mmol) and stirred for 1 h. The solution was filtered through diatomaceous earth. The solvent was slowly evaporated to give orange crystals. The crystals were washed with hexanes (3 × 1 mL) and dried in vacuo to give [4.7]OTf (135 mg, 87%) as an orange solid. 31P{1H} NMR (121 MHz, CDCl3): δ 216 (d, 1JRhP = 180 Hz); 1H NMR (400 MHz, CDCl3): δ 7.11–7.03 (m, 1H), 6.85–6.82 (m, 1H), 6.81–6.75 (m, 1H), 6.63 (br s, 1H), 6.52–6.46 (m, 1H), 6.44–6.38 (m, 1H), 6.19–6.13 (m, 1H), 5.42–5.34 (m, 1H), 4.80–4.75 (m, 1H), 4.46– 4.42 (m, 1H), 4.28–4.23 (m, 1H), 3.71 (s, 3H), 3.66–3.60 (m, 1H), 3.57–3.50 (m, 1H), 2.85–2.73 (m, 1H), 2.66–2.55 (m, 2H), 2.57 (s, 3H), 2.52–2.43 (m, 1H), 2.38–2.33 (m, 1H), 2.35 (s, 3H), 2.30–2.17 (m, 2H), 2.19 (s, 3H), 2.18 (s, 3H), 2.14–1.96 (m, 2H), 1.21 (s, 3H), 1.07 (d, 3JHH = 7 Hz, 3H), 0.99 (d, 3JHH = 7 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 181.1 (d, 1JPC = 45 Hz), 176.5 (d, 3JPC = 15 Hz), 159.6, 142.3, 141.5 (d, JPC = 9 Hz), 140.1, 131.5 (d, JPC = 11 Hz), 130.0 (d, JPC = 13 Hz), 129.2 (d, JPC = 8 Hz), 129.1 (d, JPC = 5 Hz), 126.5 (d, JPC = 11 Hz), 124.5 (dd, 1JPC = 28 Hz, 2JRhC = 5 Hz), 121.0 (q, 1JFC = 320 Hz), 113.7, 113.4, 110.5 (dd, 2JPC = 8 Hz, 1JRhC = 7 Hz), 107.9 (dd, 2JPC = 12 Hz, 1JRhC = 7 Hz), 86.7 (d, 1JRhC = 11 Hz), 75.9 (d, 1JRhC = 11 Hz), 70.9, 70.1, 55.4, 48.2 (d, JPC = 11 Hz), 39.1 (d, JPC = 16 Hz), 35.4 (d, JPC = 4 Hz), 32.9, 32.1, 29.2, 26.8, 24.0 (d, JPC = 7 Hz), 23.3 (d, JPC = 10 Hz), 22.5 (d, JPC = 4 Hz), 21.4, 18.6, 15.2.   129 4.4.7 Synthesis of [2-i-PrPhP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Rh(C8H12)•OTf ([4.8]OTf) To a solution of 2-i-PrPhP=CPhC(Me)2(CNOCH(i-Pr)CH2) (80 mg, 0.20 mmol) and [RhCl(cod)]2 (47 mg, 0.097 mmol) in CH2Cl2 (1 mL) was added AgOTf (54 mg, 0.21 mmol) and the solution was stirred for 1 h. The reaction mixture was filtered through diatomaceous earth. The solvent was evaporated to give an orange oil. The oil was triturated with pentane (1 mL), and the solid was washed with pentane (2 × 1 mL). The orange solid was dried in vacuo (100 ºC, 0.01 mmHg) to yield [4.8]OTf (34 mg, 46%) as an orange solid. 31P{1H} NMR (121 MHz, CDCl3): δ 219 (d, 1JRhP = 180 Hz); 1H NMR (300 MHz, CDCl3): δ 7.27–6.86 (m, 8H), 6.58–6.51 (m, 1H), 6.14–6.02 (m, 1H), 5.50–5.39 (m, 1H), 4.87– 4.79 (m, 1H), 4.49–4.42 (m, 1H), 4.32–4.25 (m, 1H), 4.01–3.90 (m, 1H), 3.62–3.53 (m, 1H), 3.52–3.41 (m, 1H), 2.85–2.67 (m, 1H), 2.66–2.47 (m, 3H), 2.40–2.23 (m, 3H), 2.20–1.99 (m, 2H), 1.39 (d, 3JHH = 7 Hz, 3H), 1.21 (d, 3JHH = 7 Hz, 3H), 1.17 (s, 3H), 1.07 (d, 3JHH = 7 Hz, 6H); anal. for C34H44F3NO4PRhS: C, 54.18; H, 5.88; N, 1.86; Found: C, 53.30; H, 5.77; N, 1.93.  4.4.8 Synthesis of [2-i-PrPhP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Rh(C8H12)•BF4 ([4.8]BF4) To a solution of 2-i-PrPhP=CPhC(Me)2(CNOCH(i-Pr)CH2) (51 mg, 0.13 mmol) and [RhCl(cod)]2 (22 mg, 0.044 mmol) in CH2Cl2 (1 mL) was added AgBF4 (36 mg, 0.18 mmol) and the solution was stirred for 1 h. The reaction mixture was filtered through diatomaceous earth. Cooling of the reaction mixture to −30 ºC gave X-ray quality crystals after 7 d. The mother liquor was decanted, and the crystals were washed with hexanes (3 × 1 mL) and dried in vacuo (20 ºC, 0.01 mmHg) to give [4.8]BF4 (59 mg, 96%) as orange crystals.  130 31P{1H} NMR (121 MHz, CDCl3): δ 218 (d, 1JRhP = 181 Hz); 1H NMR (CDCl3, 400 MHz): δ 7.28–6.85 (m, 8H), 6.56–6.53 (m, 1H), 6.12–6.03 (m, 1H), 5.51–5.41 (m, 1H), 4.84– 4.72 (m, 1H), 4.49–4.41 (m, 1H), 4.30–4.23 (m, 1H), 4.01–3.92 (m, 1H), 3.61–3.52 (m, 1H), 3.52–3.42 (m, 1H), 2.83–2.71 (m, 1H) 2.66–2.42 (m, 3H), 2.37 (s, 3H), 2.34–2.25 (m, 3H), 2.20–1.95 (m, 2H), 1.39 (d, 3JHH = 7 Hz, 3H), 1.21 (d, 3JHH = 7 Hz, 3H), 1.17 (s, 3H), 1.07 (d, 3JHH = 7 Hz, 6H).  4.4.9 Synthesis of [2-t-BuPhP=CPhC(Me)2(CNOCH(i-Pr)CH2)]Rh(C8H12)•OTf ([4.9]OTf) To a solution of 2-t-BuPhP=CPhC(Me)2(CNOCH(i-Pr)CH2) (22 mg, 0.045 mmol) and [RhCl(cod)]2 (10 mg, 0.020 mmol) in CH2Cl2 (1 mL) was added AgOTf (10 mg, 0.039 mmol) and the solution was stirred for 1 h. The reaction mixture was filtered through diatomaceous earth, and the solvent was allowed to evaporate to give an orange solid. The solid was washed with hexanes (3 × 1 mL) and dried in vacuo to yield [4.9]OTf (21 mg, 68%) as orange crystals. 31P{1H} NMR (121 MHz, CDCl3): δ 227 (d, 1JRhP = 181 Hz); 1H NMR (300 MHz, CDCl3): δ 7.37–7.32 (m, 1H), 7.26–7.05 (m, 6H), 7.02–6.96 (m, 1H), 6.71–6.66 (m, 1H), 5.98– 5.90 (m, 1H), 5.47–5.39 (m, 1H), 4.84–4.77 (m, 1H), 4.49–4.44 (m, 1H), 4.24–4.18 (m, 1H), 4.01–3.94 (m, 1H), 3.47–3.41 (m, 1H), 2.83–2.71 (m, 1H), 2.64–2.48 (m, 2H), 2.46–2.38 (m, 1H), 2.33 (s, 3H), 2.32–2.23 (m, 3H), 2.13–2.05 (m, 1H), 2.02–1.93 (m, 1H), 1.54 (s, 9H), 1.14 (s, 3H), 1.07 (d, 3JHH = 7 Hz, 3H), 0.99 (d, 3JHH = 7 Hz, 3H).  131 4.4.10 Synthesis of [2-t-BuPhP=CPhC(Me)2(CNOCH(i- Pr)CH2)]Rh(C8H12)•BF4 ([4.9]BF4) To a solution of 2-t-BuPhP=CPhC(Me)2(CNOCH(i-Pr)CH2) (52 mg, 0.13 mmol) and [RhCl(cod)]2 (24 mg, 0.049 mmol) in CH2Cl2 (1 mL) was added AgBF4 (25 mg, 0.13 mmol) and the solution was stirred for 1 h. The reaction mixture was filtered through diatomaceous earth, and the solvent was allowed to evaporate to give an orange solid. The solid was washed with hexanes (3 × 1 mL) and dried in vacuo to yield [4.9]BF4 (56 mg, 82%) as orange crystals. 31P{1H} NMR (162 MHz, CDCl3): δ 227 (d, 1JRhP = 181 Hz); 1H NMR (400 MHz, CDCl3): δ 7.36–7.31 (m, 1H), 7.25–7.05 (m, 6H), 7.02–6.97 (m, 1H), 6.71–6.66 (m, 1H), 5.94– 5.88 (m, 1H), 5.45–5.37 (m, 1H), 4.80–4.74 (m, 1H), 4.48–4.44 (m, 1H), 4.21–4.16 (m, 1H), 4.02–3.94 (m, 1H), 3.47–3.41 (m, 1H), 2.84–2.72 (m, 1H), 2.63–2.49 (m, 2H), 2.46–2.38 (m, 1H), 2.33 (s, 3H), 2.31–2.22 (m, 3H), 2.13–2.04 (m, 1H), 2.01–1.91 (m, 1H), 1.53 (s, 9H), 1.13 (s, 3H), 1.07 (d, 3JHH = 7 Hz, 3H), 0.99 (d, 3JHH = 7 Hz, 3H).  4.4.11 Representative Example of Rhodium Catalyzed Allylic Alkylation Rhodium complex [4.6]OTf (10 mg, 0.013 mmol) and Cs2CO3 (86 mg, 0.27 mmol) were dissolved in CH2Cl2 (1 mL) to which was added ethyl (1-phenyl allyl) carbonate (55 mg, 0.27 mmol) and dimethylmalonate (40 mg, 0.27 mmol) and stirred overnight (16 h). The reaction mixture was quenched with saturated NH4Cl (5 mL) and extracted with Et2O (3 × 5 mL). The combined organic extracts were washed with brine (5 mL), and dried over sodium sulfate. The sodium sulfate was filtered followed by the removal of the solvent in vacuo. The crude oil was purified by column chromatography using silica gel (hexanes/EtOAc, 95:5) to give dimethyl 2- (1-phenylallyl)malonate (51 mg, 77%) as a colorless oil. Spectral data matched literature.219 The  132 enantiomeric excess was determined by SFC analysis (210 nm, 20 ºC) tR 16.7 min (minor); tR 25.4 (major) [Chiralcel AD-H, CO2/i-PrOH 99:1, 100 bar, 2 mL/min] to be 20%.  4.4.12 X-ray Crystallography All single crystals were immersed in oil and mounted on a glass fiber. Data were collected on a Bruker X8 APEX diffractometer with graphite- monochromated Mo Kα radiation. All structures were solved by direct methods and subsequent Fourier difference techniques. All non-hydrogen atoms were refined anisotropically with hydrogen atoms being included in calculated positions but not refined. All data sets were corrected Lorentz and polarization effects. All calculations were performed using SHELXTL crystallographic software package from Bruker-AXS.159 Additional crystal data and details of the data collection and structure refinement are given in Table 4.4.  133  Table 4.4 Data Collection and Refinement Details of Complexes [4.5]OTf, [4.6]OTf, and [4.8]BF4.a  [4.5]OTf [4.6]OTf [4.8]BF4 formula C34H44F3IrNO4PS C34H44F3NO4PRhS C33H44BF4NOPRh fw 842.93 753.64 691.38 cryst syst orthorhombic orthorhombic trigonal space group P21,21,21 P21,21,21 P31 color red orange red a (Å) 10.1380(9) 10.1815(3) 10.8370(5) b (Å) 17.7797(17) 17.8547(4) 10.8370 c (Å) 18.8811(18) 18.8208(4) 23.557(1) α (deg) 90.00 90.00 90.00 β (deg) 90.00 90.00 90.00 γ (deg) 90.00 90.00 120.00 V (Å3) 3403.3(5) 3421.4(2) 3 T (K) 173 173 173 Z 4 4 3 µ(Mo Kα) (cm-1) 4.086 0.661 0.635 cryst size (mm3) 0.3×0.2×0.1 0.5×0.4×0.2 0.6×0.1×0.1 calcd density (Mg m-3) 1.645 1.463 1.438 2θ(max) (deg) 56.0 55.82 48.51 no. of reflns 52028 25431 30634 no. of unique data 8189 8166 7507 R(int) 0.0616 0.0337 0.0278 refln/param ratio 19.83 19.77 18.96 R1b 0.0609; I > 2σ(I) 0.0415; I > 2σ(I) 0.0306; I > 2σ(I) wR2 (all data)c 0.0634 0.0545 0.1343 GOF 1.028 1.038 1.061 a Adapted with permission from Angew. Chem. Int. Ed., 2008, 47, 8064-8067. © 2008 Wiley- VCH Verlag GmbH & Co. KGaA. b R1 = Σ||Fo|-|Fc|/Σ|Fo|. c wR2(F2[all data]) = {Σ[w(Fo2 – Fc2)2/Σ[w(Fo2)2]}1/2  Data removed for Copyright Reasons. Data is found in Table 1 of the original source’s supporting information. Julien Dugal- Tessier, Gregory. R. Dake and Derek P. Gates. Chiral Ligand Design: A Bidentate Ligand Incorporating an Acyclic Phosphaalkene. Angewandte Chemie, International Edition, 2008, 47, 8064-8067. © 2008 Wiley- VCH Verlag GmbH & Co. KGaA.  134 CHAPTER 5 Chiral Phosphaalkene–Oxazoline Ligands for the Palladium-Catalyzed Asymmetric Allylic Alkylation Reactions* 5.1 Introduction This chapter reports a breakthrough in the evolution of low-coordinate phosphorus ligands for catalysis, namely, the application of enantiomerically pure phosphaalkene-oxazolines (PhAk–Ox) in the Pd-catalyzed asymmetric allylic alkylation. Palladium complexes of PhAk–Ox ligands were also structurally characterized. The results demonstrate that the PhAk–Ox ligand class gives synthetically useful yields and high enantiomeric excesses (ee’s) using a range of functionalized β-dicarbonyl nucleophiles in allylic alkylation reactions. The Pd-catalyzed alkylation of allylic substrates using PhAk–Ox’s was selected to assess the potential of the PhAk–Ox ligands in asymmetric catalysis. These ligands bear a rough resemblance to the highly successful Pfaltz–Helmchen P(sp3),N(sp2) phosphinooxazoline (PHOX) ligands.220-222 The successful implementation of PhAk–Ox in catalytic asymmetric allylic alkylation provides an entry point to broader application in asymmetric catalysis. Moreover, these experiments also provide a benchmark for the development of later generations versions of the PhAk–Ox ligand system.   * A version this chapter has been published. Julien Dugal-Tessier, Gregory R. Dake and Derek P. Gates. Chiral Phosphaalkene–Oxazoline Ligands for the Palladium-Catalyzed Asymmetric Allylic Alkylation. Organic Letters, 2010, 12, 4667-4669.  135 O NAr2P R phosphinooxazoline (PHOX) P C O N Ar R phosphaalkene-oxazoline (PhAk-Ox) Figure 5.1 Structure of PHOX and PhAk–Ox Proligands.  The mechanistic details of asymmetric palladium-catalyzed allylic alkylation have been investigated (Scheme 5.1).132,200,223,224 The catalytic cycle starts with a Pd(0) complex (I) that coordinates an olefin (II). Ionization then leads to palladium π-allyl complex (III). This complex (III), depending on the conditions, the ligand, and the metal can undergo a π-σ-π interconversion. Nucleophilic attack at both termini of the palladium allyl complex anti to the metal generates isomeric olefin complexes (IV). Decomplexation of the metal regenerates the palladium(0) catalyst (I). All the steps in the cycle, except decomplexation, have the potential to be the enantiodescriminating step and more than one step can be involved in the observed enantioselectivity.132   136 Pd L L R X R X Pd LL R Pd LL R PdL2 X R Pd LL Nu R Nu or R Nu Pd LL Pd LL R Nu or R Nu -X Complexation ionizationnucleophilic addition decomplexation R' R'R' R' R' R' R' R' I III IIIV R'  Scheme 5.1 Postulated Generalized Mechanism for Allylic Alkylation.132  One mode of enantiodescrimination has been the desymmetrization of a meso palladium allyl system (Scheme 5.2). Once the symmetric palladium allyl complex (VI) is formed, nucleophilic attack of one terminus has to be much faster than attack at the other terminus leading to enantioenriched product (VII).225 The desymmetrization of meso-allyl complexes has been very successful with the PHOX ligand set and therefore is a good benchmark to measure the reactivity of the PhAk–Ox ligands. LG Pd L L * Nu Nu Nu [PdL2*] Nu LG VIIVIV fast slow  Scheme 5.2 Desymmetrization of π-Allyl Systems.225   137 Detailed studies of the enantiodescriminating step of the PHOX ligands in the desymmetrization of the palladium allyl system have been performed. It was observed that attack of the nucleophile is predominantly trans to the more π acidic phosphorus in the exo conformation (Scheme 5.3).226-228 Enantioselectivities are affected by the ratio of exo and endo isomers, relative rate of interconversion between isomers and the relative rate of nucleophilic attack of isomers.229-233 Studies by Bunt234 seem to indicate that a greater electronic differentiation between the phosphorus π-accepting properties and the nitrogen σ donation properties lead to higher enantioselectivity. Phosphaalkenes are better π acceptors than phosphines and should therefore be a suitable ligand for this reaction. O N Pd P i-Pr Ph Ph Ph exo Nu 9 : 1 O N Pd P i-Pr Ph Ph Ph endo Nu Ph Nu Ph Ph Nu Ph Scheme 5.3 Rationale for the Enantiodescriminating Step.225  5.2 Results and Discussion 5.2.1 Synthesis of Complex [5.1]OTf and 5.2 The Pd-catalyzed allylic alkylation necessitated the synthesis of the PhAk–Ox-palladium allyl complex [5.1]OTf from the reaction of [(C3H5)PdCl]2, AgOTf and 3.9a in CH2Cl2. Complex [5.1]OTf was chosen because palladium allyls are part of the catalytic cycle and is a common  138 starting metal complex for palladium catalyzed allylic alkylation.200 Complex [5.1]OTf was isolated in high yield from phosphaalkene 3.9a. The 31P{1H} NMR spectra revealed two resonances at δ = 208 and 209, which are consistent with the presence of the exo and endo isomer (Scheme 5.4). Unable to obtain a solid-state molecular structure of [5.1]OTf, complex 5.2 [δ(31P) = 192] was obtained upon reaction of 3.9a with Pd(cod)Cl2 in 63% isolated yield. A solid state molecular structure of palladium(II) complex 5.2 was obtained upon layering hexanes on a saturated solution of CH2Cl2 (Figure 5.2). Metrical parameters are similar to other metal PhAk– Ox complexes (Ir complex [4.5]OTf and Rh complex [4.6]OTf). The Pd–P bond length is shorter in 5.2 [2.186(1) Å] than analogous PHOX·PdCl2 [2.217(3) Å],235 but longer than [MesP=CPh(2- py)]·PdCl2 (2.5) [2.1749(7) Å]. The Pd–N bond length in 5.2 [2.022(2) Å] is similar than PHOX·PdCl2 [2.034(8) Å],235 but shorter than 2.5 [2.076(2) Å]. Ph C P Mes O N 3.9a Ph C P Mes O N Pd [5.1]OTf OTf CH2Cl2 1. [(C3H5)PdCl]2 2. AgOTfPd(cod)Cl2 CH2Cl2 Ph C P Mes O N Pd ClCl 87%63% 5.2 Scheme 5.4 Synthesis of Palladium Complexes of 3.9a.  139  Figure 5.2 Molecular Structure of 5.2 (50% Probability Ellipsoids). All hydrogen atoms and the solvent (CH2Cl2) are omitted for clarity. Selected bond length (Å) and angles (deg): C1–P1 = 1.796(2), C10–P1 = 1.661(2), C10–C11 = 1.479(3), C10–C17 = 1.545(3), C17–C20 = 1.510(3), C20–N1 = 1.278(3), C20–O1 = 1.332(3), N1–Pd1 = 2.022(2), P1–Pd1 = 2.186(1), Cl1–Pd1 = 2.2727(13), Cl2–Pd1 = 2.3404(12); C17–C10–P1 = 118.30(16), C11–C10–P1 =120.99(16), C20–C17–C10 = 109.82(17), N1–C20–O1 = 116.3(2), N1–C20–C17 = 128.4(2), O1–C20–C17 = 115.34 (18), C20–N1–Pd1 = 129.12(17), C10–P1–C1 = 114.8(1), C10–P1–Pd1 = 118.94(9), C1–P1–Pd1 = 126.16(8), P1–Pd1–Cl1 = 90.27(3), N1–Pd1–Cl2 = 91.37(7). Reproduced with permission from Org. Lett., 2010, 12, 4667-4669. © 2010 American Chemical Society.   5.2.2 Catalytic Activity of Palladium Complexes [5.1]OTf and [5.7]OTf The Pd-complex [5.1]OTf showed considerable potential in allylic alkylation. For example, the reaction between racemic 1,3-diphenyl-2-propenyl ethyl carbonate and dimethyl malonate in the presence of [5.1]OTf (5 mol %) afforded the substituted malonate (5.9) with a very promising 83% ee, albeit in modest isolated yield (35%) (Table 5.1, entry 1). Efforts to  140 optimize the performance of [5.1]OTf by employing different base systems resulted in a major breakthrough with N,O-bis(trimethylsilyl)acetamide (BSA) and potassium acetate which improved the isolated yield of 5.9 to 70% while maintaining enantioselectivity (85% ee) (Table 5.1, entry 3). Table 5.1 Initial Results Using PhAk–Ox Pd Complexes [5.1]X and [5.7]X in Asymmetric Allylic Alkylation.a Ph Ph LG base CH2Cl2 (20 ºC) Ph Ph CH(CO2Me)2 H2C(CO2Me)2+ Ph C P Mes O N R R Pd [5.1]X (R = H) [5.7]X (R = Me)5 mol % X 5.9 entry LG catalyst baseb % yieldc % eed,e 1 OCO2Et [5.1]OTf NaH 35 83 2 OCO2Et [5.1]OTf Cs2CO3 36 50 3 OCO2Et [5.1]OTf BSA/KOAc 70 85 4 OCO2Et [5.7]OTf BSA/KOAc 74 91 5 OCO2Et [5.7]BF4 BSA/KOAc 52 70 6 OAc [5.7]OTf BSA/KOAc 83 92 a Adapted with permission from Org. Lett., 2010, 12, 4667-4669. © 2010 American Chemical Society. b NaH (1 equiv); Cs2CO3 (1 equiv); BSA (1 equiv)/KOAc (0.01 equiv). c Isolated yields. d ee was determined using chiral SFC-HPLC. e ee’s are ±3% and best out of 2 run  In an effort to further improve the enantioselectivity of this process, modifications to the ligand skeleton were undertaken. In the PHOX ligand series, it was found that the addition of a gem-dialkyl moiety at C5 of the 4-i-Pr–Ox results in higher enantioselectivities because it has similar sterics properties as the 4-t-Bu–Ox.236-238 The presence of gem-dialkyl groups influences the positioning of the i-Pr methyl moieties with respect to the metal center, thus increasing the enantioselectivity. Synthesis of C5 dimethyl allyl complex 5.7[OTf] is shown in Scheme 5.5. Large quantities of the amino alcohol (5.3) could be obtained in four steps from L-valine following a route developed by Denmark (Scheme 5.5).239 Condensation with isobutyric acid generated  141 oxazolines 5.4 and Claisen-type condensation gave ketone 5.5. Phospha-olefination using the phospha-Peterson reaction generated proligand 5.6. The palladium allyl complex [5.7]OTf, was then prepared following analogous procedures to those outlined above. Complex [5.7]OTf showed only one resonance by 31P{1H} NMR δ = 212, which suggest that only one of the isomer is formed. NH3 +Cl- MeO O (CF3CO)2O, Et3N, CH2Cl2, 0 ºC H N MeO O CF3 O MeMgI in Et2O THF, 0 ºC H N HO CF3 O 1M NaOH EtOH, reflux O OH xylenes Dean–Stark O N Ph C O O N sec-BuLi, TMEDA THF, -78 ºC; then PhCO2Et 1)MesP(SiMe3)Li THF, -78 ºC 2)Me3SiCl THF, –78 ºC Ph C P O N Mes HO NH2 O SOCl2, MeOH quant. 82% 63% 92% NH2 HO Ph C P Mes O N Pd [5.7]OTf OTf CH2Cl2 1) [(C3H5)PdCl]2 2) AgOTf 5.3 L-valine 5.4 5.5 5.6 60% 57% 65% 73%  Scheme 5.5 Synthesis of Phosphaalkene 5.6 and Complex [5.7]OTf.  Attempts to ascertain the orientation of the i-Pr methyl moieties in [5.7]OTf through X- ray diffraction were unsuccessful since suitable crystals could not be obtained. Thus, PdCl2 complex 5.8 (Scheme 5.6) was prepared [δ(31P) = 191] and analyzed crystallographically to reveal three conformational forms in the asymmetric unit (Figure 5.3). In the solid-state, two of the three isomers (b and c, 60%) have the methyl groups on the isopropyl moiety projecting towards the Pd atom in 5.8. This contrasts with 5.2 in which the methyl groups on the isopropyl unit are oriented away from the Pd atom in the solid-state (Figure 5.2). Metrical parameters of 5.8 are very similar to 5.2 except for the Mes–P=C angle which is more acute [111.7(1)º for 5.8  142 compared with 114.8(2)º for 5.2]. The more acute angle is most likely due to steric interactions between an ortho-methyl of the Mes group and the oxazoline isopropyl group. Ph C P Mes O N 5.6 Pd(cod)Cl2 CH2Cl2 Ph C P Mes O N Pd ClCl 68% 5.8 Scheme 5.6 Synthesis of complex 5.8.  Importantly, the use of the modified catalyst [5.7]OTf led to improved performance in allylic alkylation. Malonate 5.9 was obtained in high enantioselectivity (91%; cf. 85% for [5.1]OTf) and good yield (74%; cf. 70% with [5.1]OTf) (Table 5.1, entry 4). Changing the catalyst counterion to [BF4]– gave poorer results (Table 5.1, entry 5). In the midst of these optimization experiments, it was observed that product mixtures were often contaminated with 1,3-diphenyl-2-propenyl ethyl ether. This undesired side-product results from the addition of ethoxide (formed from EtOCO2–) to the putative π-allyl intermediate. This has been observed previously and is avoided by employing acetate as the leaving group.240,241 To our delight, racemic 1,3-diphenyl-2-propenyl acetate reacted readily with dimethyl malonate using catalyst [5.7]OTf to afford 5.9 in 83% yield and 92% ee (Table, 1 entry 6), an improvement over the analogous carbonate (74%, 91% ee). Modification of the ligand framework generated a PhAk– Ox ligand that gave synthetically useful yields and enantioselectivities.   143   Figure 5.3 Molecular Structures Showing the Three Conformations of 5.8 in the Solid State: (a) 40%, (b) 37%, (c) 23% (50% probability ellipsoids). All hydrogen atoms are omitted for clarity. Selected bond length (Å) and angles (deg) for 5.8a: C1–P1 = 1.800(2), C10–C11 = 1.480(4), C10–C17 = 1.511(8), C10–P1 = 1.669(3), C20–C17 = 1.484(6), N1–C20 = 1.275(5), C20–O1 = 1.340(4), N1–Pd1 = 2.013(5), P1–Pd1 = 2.1793(7), Cl1–Pd1 = 2.3497(6), Cl2–Pd1 = 2.2835(6); C17–C10–P1 = 118.5(3), C11–C10–P1 = 118.5(2), C20–C17–C10 = 115.4(4), N1–C20–O1 = 115.4(4), N1–C20–C17 = 128.6(4), O1–C20–C17 = 116.0(4), C20–N1–Pd1 = 128.4(4), C10–P1–C1 = 111.7(1), C10–P1–Pd1 = 118.34(9), C1–P1– Pd1 = 129.4(9), P1–Pd1–Cl2 = 88.67(2), N1–Pd1–Cl1 = 91.3(2). Reproduced with permission from Org. Lett., 2010, 12, 4667-4669. © 2010 American Chemical Society.  144  5.2.3 Scope of Palladium Catalyzed Allylic Substitution with [5.7]OTf The encouraging results described in the preceding section led us to investigate the scope of nucleophiles in allylic alkylations with 1,3-diphenyl-2-propenyl acetate catalyzed by [5.7]OTf. The enantioselectivities and the isolated yields are summarized in Figure 5.4 and generally show [5.7]OTf to be an effective catalyst. A few points merit comment. The dibenzyl malonate 5.11 was formed in lower yield and enantioselectivity relative to its dimethyl (5.9) or diethyl (5.10) congeners. Diketone 5.13, formed by the addition of acetylacetone to 1,3- diphenyl-2-propenyl acetate, was produced in 88% ee but only in 40% yield. Importantly, β- dicarbonyl compounds that contain ether or alkene functions are also well tolerated in reactions catalyzed by [5.7]OTf, giving alkylated malonates 5.14–5.17 in good yields with excellent enantioselectivities. CMe(CO2Me)2 PhPh CH(CO2Bn)2 PhPh CH(CO2Et)2 PhPh PhPh PhPh CO2Me CO2Me PhPh CO2Me CO2Me 5.12 73% (91% ee) 5.11 76% (79% ee) 5.10 81% (91% ee) 5.13 40% (88% ee) 5.16 85% (89% ee) 5.17 95% (92% ee) Ph Ph OAc Nu-H BSA/KOAc CH2Cl2 (20 ºC) Ph Ph Nuc OO + Ph C P Mes O N Me Me Pd [5.7]OTf OTf5 mol % PhPh BnO CO2Me CO2Me PhPh TBSO CO2Me CO2Me 5.14 73% (89% ee) 5.15 74% (89% ee) Figure 5.4 Preliminary Investigation of the Scope of Enantioselective Allylic Alkylation Using PhAk–Ox Catalyst [5.7]OTf Indicating Functional Group Tolerance.   145 Acyclic dialkenes 5.16 and 5.17 can be further synthetically manipulated using catalytic amounts (5 mol %) of the Grubbs II catalyst, [(IMes)(PCy3)RuCl2(=CHPh)].242 The ring-closing metathesis of 5.16 and 5.17 proceeded smoothly to produce cyclopentene 5.18 and cyclohexene 5.19 in good yields (Scheme 5.7). Importantly, HPLC analysis of the starting materials and products in this sequence demonstrated that no erosion of the stereochemical configuration took place. Grubbs II Ph n 5.18, n = 1, 85% (89% ee) 5.19, n = 2, 87% (90% ee) PhPh CO2Me CO2Me CH2Cl2 CO2Me CO2Me 5.16, n = 1, 89% ee 5.17, n = 2, 90% ee n H H  Scheme 5.7 Ring Closing Metathesis of 5.16 and 5.17.  5.3 Summary This work demonstrates the first application of a chiral phosphaalkene (PhAk) derived ligand that supports metal-catalyzed processes for organic chemistry in high yields and enantioselectivities. The modular nature within the ligand design bodes well for utility and optimization in other applications involving metal catalysis.  5.4 Experimental Section 5.4.1 General Procedures    All manipulations of air- and/or water- sensitive compounds were performed under a nitrogen atmosphere using standard Schlenk or glovebox techniques. Hexanes and dichloromethane (CH2Cl2) were deoxygenated with nitrogen and dried by passing through a  146 column containing activated alumina. Tetrahydrofuran (THF) was dried over sodium and benzophenone. 230-400 mesh silica was used (Silicycle). Isobutyric acid, ethyl benzoate, chlorotrimethylsilane (TMSCl), xylenes, dimethyl malonate, diethyl malonate, dibenzyl malonate, acetylacetone, the Grubbs II catalyst and N,O-bis(trimethylsilyl) acetamide (BSA) were purchased from Aldrich and used as received. Dichloro(1,5-cyclooctadiene)palladium(II), PdCl2(cod),150 and allylpalladium(II) chloride dimer, [(C3H5)PdCl]2,243 were prepared according to literature. N,N,N’,N’-tetramethylethylenediamine (TMEDA) was purchased from Aldrich and distilled over sodium prior to use. Potassium acetate (KOAc) was purchased from Aldrich and dried at 60 °C in vacuo before use. sec-Butyllithium and methyllithium were purchased from Aldrich and titrated using N-benzylbenzamide.186 1H, 31P, 13C{1H} NMR spectra were recorded at 25 °C on Bruker Avance 300 or 400 MHz spectrometers. 85% H3PO4 was used as an external standard (δ = 0.0 for 31P). 1H NMR spectra were referenced to residual protonated solvent and 13C NMR were referenced to the deuterated solvent. Elemental analyses were performed in the University of British Columbia Chemistry Microanalysis Facility. Mass spectra were recorded on a Kratos MS 50 instrument in EI mode (70 eV). Melting points are uncorrected. The optical rotations were measured at a concentration in g/100 mL and their values (average of 10 measurement) were obtained on a Jasco P-1010 polarimeter. Enantiomeric excess were determined using a Thar SFC equipped with a photodiode array. 5.4.2 Synthesis of (S)-2,4-diisopropyl-5,5-dimethyl-4,5-dihydrooxazole (5.4) A modified literature procedure was used.162 To a solution of (S)-3-amino-2,4- dimethylpentan-2-ol (25.0 g, 190 mmol) in xylenes (0.5 M) was added isobutyric acid (17.6 mL, 190 mmol) and the mixture was heated to reflux using a Dean-Stark apparatus for 36 h. The reaction mixture was cooled and extracted with 10% aqueous hydrochloric acid solution and the  147 aqueous layer was neutralized with 40% aqueous sodium hydroxide. The aqueous layer was extracted with Et2O (3 × 60 mL) and the combined organic extracts were dried using sodium sulfate. The solvent was removed by rotary evaporation in vacuo, and the oxazoline was purified by bulb-to-bulb distillation to afford (S)-2,4-diisopropyl-5,5-dimethyl-4,5-dihydrooxazole (20.8 g, 60%) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 3.24 (d, JHH = 7 Hz, 1H), 2,56 (sept, JHH = 7 Hz, 1H), 1.85–1.69 (m, 1H), 1.39 (s, 3H), 1.29 (s, 3H), 1.17 (d, JHH = 7 Hz, 3H), 1.16 (d, JHH = 7 Hz, 3H), 1.03 (d, JHH = 7 Hz, 3H), 0.98 (d, JHH = 7 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 169.8, 85.3, 79.2, 28.9, 28.8, 28.4, 21.1, 20.8, 19.8,19.4; IR (neat): 2966, 2875, 1640, 1543, 1469, 1370, 1160 cm-1; HRMS (ESI) calcd for [C11H21NO + H]+ 184.1701; Found 184.1698; [α]D22 –55.1 (c 1.03, CH2Cl2) 5.4.3 Synthesis of (S)-2-(4-isopropyl-5,5-dimethyl-4,5-dihydrooxazol-2-yl)-2- methyl-1-phenylpropan-1-one (5.5)   To a solution of (S)-2,4-diisopropyl-5,5-dimethyl-4,5-dihydrooxazole (18.6 g, 101 mmol) in THF (350 mL) at −78 °C was sequentially added TMEDA (15 mL, 101 mmol) and sec-BuLi (75 mL, 101 mmol, 1.35 M). After the solution was stirred for 1 h at −78 °C, ethyl benzoate (16 mL, 111 mmol) was added dropwise to the reaction mixture. The reaction mixture was warmed to rt and stirred for 30 min. Water (30 mL) and saturated aqueous ammonium chloride solution (30 mL) were carefully added to the reaction mixture. The aqueous layer was extracted with diethyl ether (3 × 200 mL). The organic fractions were combined, dried using sodium sulfate, and concentrated by rotary evaporation in vacuo. The residue was purified by fractional bulb-to-  148 bulb distillation under reduced pressure to afford PhCOCMe2(CNOCH(i-Pr)CMe2) (15.2g, 57%) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 8.02–7.97 (m, 2H), 7.50–7.43 (m, 1H), 7.40–7.33 (m, 2H), 3.26 (d, JHH = 8 Hz, 1H), 1.82–1.68 (m, 1H), 1.58 (s, 3H), 1.56 (s, 3H), 1.16 (s, 3H), 1.09 (d, JHH = 7 Hz, 3H), 1.06 (s, 3H), 0.95 (d, JHH = 7 Hz); 13C{1H} NMR (75 MHz, CDCl3): δ 199.1, 167.7, 135.9, 132.4, 128.9, 128.1, 86.6, 80.2, 48.3, 29.2, 29.0, 24.7, 24.5, 21.3, 21.0, 20.6; IR (neat): 2974, 1691, 1656 cm-1; HRMS (ESI) calcd for [C18H25NO2 + H]+ 288.1964; Found 288.1967; [α]D22 –48.8 (c 1.1, CH2Cl2). 5.4.4 Synthesis of MesP=CPhCMe2(CNOCH(i-Pr)CMe2) (5.6) To a solution of MesP(SiMe3)275 (8.25 g, 27.8 mmol) in THF (50 mL) was added MeLi in Et2O (1.5 M, 18.5 mL, 27.8 mmol). The mixture was heated to 55 °C for 2 h. An aliquot removed for analysis by 31P{1H} NMR spectroscopy revealed a single resonance at −187 ppm, attributable to MesP(SiMe3)Li. The reaction mixture was cooled to −78 ºC after which a solution of PhCOCMe2(CNOCH(i-Pr)CMe2) (8.0 g, 27.8 mmol) in THF (10 mL) was added dropwise. 31P{1H} NMR spectroscopy of an aliquot indicated one resonance, assigned as a phosphaalkene. The solution was quenched by the addition of TMSCl (5.8 g, 27.8 mmol). The solvent was removed in vacuo to give a yellow solid. This material was washed with hexanes (3 × 20 mL) and the washes were filtered through a cannula filter. The solvent was removed in vacuo and the phosphaalkene was bulb-to-bulb distilled under vacuum (0.04 mmHg) to yield a yellow oil that solidified upon standing to yield 5.6 (7.65 g, 65%) as a yellow solid. 31P{1H} NMR (121 MHz, CDCl3): δ 245 ppm; 1H NMR (400 MHz, CDCl3): δ 6.99–6.93 (m, 3H), 6.86–6.82 (m, 2H), 6.60–6.56 (m, 2H), 3.22 (d, JHH = 8 Hz, 1H), 2.27 (s, 3H), 2.23 (s,  149 3H), 2.10 (s, 3H), 1.78–1.68 (m, 1H), 1.65 (s, 3H), 1.60 (s, 3H), 1.40 (s, 3H), 1.29 (s, 3H), 1.00 (d, JHH = 7 Hz, 3H), 0.96 (d, JHH = 7 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 203.2 (d, JPC = 48 Hz), 168.6 (d, JPC = 8 Hz), 143.0 (d, JPC = 14 Hz), 140.0 (d, JPC = 7 Hz), 139.9 (d, JPC = 6 Hz), 137.8, 136.3 (d, JPC = 41 Hz), 128.0 (d, JPC = 5 Hz), 127.0, 126.9, 126.8, 126.3, 86.1, 80.4, 47.2 (d, JPC = 25 Hz), 29.7, 29.4, 28.3 (d, JPC = 14 Hz), 28.1 (d, JPC = 11 Hz), 22.6 (d, JPC = 9 Hz), 22.5 (d, JPC = 8 Hz), 21.6, 21.5, 21.1, 20.8; HRMS calcd for C27H36NOP: 421.2535; Found: 421.2534; LRMS (EI): m/z [%]: 422, 421 [3,9, M+], 407, 406 [29, 100, M+ − Me], 311, 310 [9, 43, M+ − C7H13N], 303, 302 [2, 7, M+ − Mes], 91 [15, C7H7+]; mp 41–44 °C; [α]D27 –70.0 (c 4.4, CH2Cl2). 5.4.5 Synthesis MesP=CPhCMe2(CNOCH(i-Pr)CH2)PdCl2 (5.2) To a solution of 3.9a(228 mg, 0.57 mmol) in CH2Cl2 (1.5 mL) was added PdCl2(cod) (154 mg, 0.53 mmol). The solution was stirred until all the solids were dissolved. The reaction mixture was layered with pentane and cooled at −26 °C overnight. The supernatant was removed and the solids (X-ray quality crystals) were washed with hexanes (3 × 2 mL) and dried in vacuo for 16 h to generate crystals of 5.2 (219 mg, 63%). 31P{1H} NMR (121 MHz, CDCl3): δ 192; 1H NMR (300 MHz, CDCl3): δ 7.27–7.03 (m, 4H), 6.76–6.70 (m, 1H), 6.66–6.57 (m, 2H), 5.42–5.32 (m, 1H), 4.49–4.46 (m, 2H), 2.90–2.82 (m, 1H), 2.55 (d, JHH = 2 Hz, 3H), 2.39 (d, JHH = 2 Hz, 3H), 2.17 (s, 3H), 2.13 (s, 3H), 1.16 (s, 3H), 1.02 (d, JHH = 7 Hz, 3H), 0.96 (d, JHH = 7 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 177.7 (d, JPC = 55 Hz), 173.7 (d, JPC = 16 Hz), 143.0 (d, JPC = 3 Hz), 142.6 (d, JPC = 3 Hz), 141.0 (d, JPC = 7 Hz), 137.8 (d, JPC = 10 Hz), 129.0 (d, JPC = 1 Hz), 128.6, 128.5, 128.4, 128.2, 128.0 (d, JPC = 16 Hz), 125.4 (d, JPC = 16 Hz), 123.0 (d, JPC = 47 Hz), 70.4, 69.9, 47.4 (d, JPC = 7 Hz), 35.2 (d, JPC = 17 Hz), 30.5, 24.9 (d, JPC = 8 Hz), 23.7 (d, JPC = 9 Hz), 23.5 (d, JPC = 5 Hz), 21.5, 18.5, 14.7;  150 anal. calcd for C25H32NOPPdCl2⋅CH2Cl2: C, 47.62; H, 5.23; N, 2.14; Found: C, 47.58; H, 5.26; N, 2.15. 5.4.6 Synthesis of MesP=CPhCMe2(CNOCH(i-Pr)CMe2)PdCl2 (5.8) To a solution of 5.6 (50 mg, 0.12 mmol) in CH2Cl2 (1 mL) was added PdCl2(cod) (34 mg, 0.12 mmol). The reaction mixture was layered with hexanes and cooled at −26 °C overnight. The yellow crystals were washed with hexanes (3 × 1 mL) to yield 5.8 (48 mg, 68%) as a yellow solid. X-ray quality crystals were obtained by recrystallization of 5.8 (14 mg) by slow evaporation of CH2Cl2. 31P{1H} NMR (121 MHz, CDCl3): δ 191 ppm; 1H NMR (400 MHz, CDCl3): δ 7.25–7.22 (m, 1H), 7.19–7.13 (m, 2H), 7.08–7.02 (m, 1H), 6.76–6.73 (m, 1H), 6.65–6.60 (m, 2H), 5.07 (d, JHH = 2 Hz, 1H), 2.59 (d, JHH = 2 Hz, 3H), 2.41 (d, JHH = 2 Hz, 3H), 2.23–2.13 (m, 1H), 2.15 (s, 3H), 2.13 (s, 3H), 1.63 (d, JHH = 7 Hz, 3H), 1.57 (s, 3H), 1.47 (s, 3H), 1.15 (s, 3H), 0.99 (d, JHH = 6 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 176.6 (d, JPC = 55 Hz), 172.9 (d, JPC = 16 Hz, 143.0 (d, JPC = 4 Hz), 142.8 (d, JPC = 2 Hz), 141.2 (d, JPC = 8 Hz), 128.8 (d, JPC = 2 Hz), 128.7, 128.7 (d, JPC = 2 Hz), 128.6, 128.5, 128.3, 128.1, 125.4 (d, JPC = 15 Hz), 123.2 (d, JPC = 45 Hz), 90.7, 76.4, 47.7 (d, JPC = 8 Hz), 34.0 (d, JPC = 18 Hz), 29.4, 27.9, 25.1 (d, JPC = 8 Hz), 24.0 (d, JPC = 10 Hz), 23.5 (d, JPC = 5 Hz), 22.2, 21.6, 20.8, 17.1; anal. calcd for C27H36Cl2NOPPd: C, 54.15; H, 6.06; N, 2.34; Found: C, 53.83; H, 6.10; N, 2.43. 5.4.7 Synthesis of MesP=CPhCMe2(CNOCH(i-Pr)CH2)PdC3H5⋅OTf ([5.1]OTf) A solution of [PdCl(C3H5)]2 (49 mg, 0.13 mmol) and 3.9a (107 mg, 0.27 mmol) in CH2Cl2 (1 mL) was stirred for 1 h. AgOTf (70 mg, 0.27 mmol) was added and the reaction  151 mixture stirred for 1 h. The reaction mixture was filtered through diatomaceous earth, and the solvent was allowed to evaporate to give a yellow oil. The oil was triturated with hexanes (1.5 mL) and the resulting solid washed with hexanes (2 × 2 mL). The solid was dried under vacuum (0.01 mmHg) for 4 h to yield [5.1]OTf as a yellow solid (162 mg, 87%). 31P{1H} NMR (121 MHz, CDCl3): δ 209, 208 ppm; 1H NMR (400 MHz, CDCl3): δ 7.18– 7.09 (m, 3H), 7.02–6.80 (m, 2H), 6.75–6.65 (m, 2H), 5.95–5.78 (br s, 1H), 5.18–4.95 (br s, 1H), 4.74–4.62 (m, 2H), 4.46–4.38 (m, 1H), 4.36–3.80 (br s, 1H), 3.55–3.10 (br s, 2H), 2.41 (s, 3H), 2.36 (s, 3H), 2.23–2.18 (m, 1H), 2.16 (s, 3H), 1.80 (s, 3H), 1.41 (s, 3H), 1.04 (d, JHH = 7 Hz, 3H), 0.93–0.84 (br s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 188.9 (d, JPC = 32 Hz), 175.5 (d, JPC = 8 Hz), 142.1, 140.5–140.1 (br s), 139.9–139.5 (br s), 138.3 (d, JPC = 12 Hz), 122.4–122.1 (br s), 121.2 (q, JFC = 321 Hz), 76.7, 69.3, 55.9, 48.7, 48.6, 32.6–32.0 (br s), 31.6–31.3 (br s), 28.2–27.8 (br s), 23.2 (d, JPC = 8 Hz), 23.0 (d, JPC = 8 Hz), 21.3, 18.6, 15.0. anal. calcd for C29H37NO4F3PPdS: C, 50.48; H, 5.40; N, 2.03; Found: C, 50.93; H, 5.64; N, 2.19. 5.4.8 Synthesis of MesP=CPhCMe2(CNOCH(i-Pr)CMe2)PdC3H5⋅OTf ([5.7]OTf)   A solution of [PdCl(C3H5)]2 (50 mg, 0.14 mmol) and 5.6 (118 mg, 0.28 mmol) in CH2Cl2 (1 mL) was stirred for 1 h, then AgOTf (73 mg, 0.28 mmol) was added and the mixture stirred for 1 h. The solution was filtered through diatomaceous earth, and the solvent was allowed to evaporate. The resulting oil was triturated with hexanes (1.5 mL) and the solid washed with hexanes (2 × 2 mL). The solid was dried under vacuum (0.01 mmHg) for 4 h to yield a yellow solid (147 mg, 73%).  152 31P{1H} NMR (121 MHz, CDCl3): δ 212 ppm; 1H NMR (300 MHz, CDCl3): δ 7.23–7.13 (m, 3H), 7.08–6.97 (m, 1H), 6.77–6.71 (m, 3H), 5.95–5.80 (br s, 1H), 5.13–5.05 (m, 1H), 4.35– 3.95 (br s, 1H), 4.01 (d, JHH = 2 Hz, 1H), 3.60–2.90 (br s, 2 H), 2.41 (s, 3H), 2.40 (s, 3H), 2.22– 2.15 (m, 1H), 2.19 (s, 3H), 1.92 (s, 3H), 1.63 (s, 3H), 1.58 (s, 3H), 1.29 (s, 3H), 1.25 (d, JHH = 7 Hz, 3H), 0.98 (d, JHH = 7 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 189.2 (d, JPC = 34 Hz), 174.9 (d, JPC = 8 Hz), 142.3, 140.0 (d, JPC = 4 Hz), 138.6, 138.5, 129.1 (d, JPC = 7 Hz), 128.9 (d, JPC = 8 Hz), 128.6, 128.1, 127.3 (br s), 126.1 (br s), 122.5 (d, JPC = 6 Hz), 121.2 (q, JFC = 321 Hz), 89.7, 84.1, 55.4 (d, JPC = 5 Hz), 48.4 (d, JPC = 8 Hz), 34.4 (d, JPC = 17 Hz), 29.6, 28.4, 26.2 (d, JPC = 8 Hz), 23.4 (d, JPC = 9 Hz), 22.8 (d, JPC = 8 Hz), 21.8, 21.3, 20.6, 16.9; anal. calcd for C31H41F3NO4PSPd: C, 51.85; H, 5.75; N, 1.95; Found: C, 52.25; H, 5.93; N, 1.98.  5.4.9 Representative Procedure for Allylic Alkylation. Synthesis of (S,E)- dimethyl 2-(1,3-diphenylallyl)malonate (5.9)  To a solution of [5.7]OTf (10 mg, 0.014 mmol), potassium acetate (2 mg) in CH2Cl2 (1.5 mL) was added 1,3-diphenyl-2-propenyl acetate (71 mg, 0.28 mmol). Dimethyl malonate (87 mg, 0.66 mmol) and BSA (122 mg, 0.60 mmol) were added dropwise in consecutive additions. The reaction mixture was stirred at 20 °C for 16 h. The reactions were quenched by the addition of a saturated NH4Cl solution (5 mL). The reaction mixture was extracted with Et2O (3 × 10 mL) and the combined organic fractions were washed with brine (10 mL) and dried over Na2SO4. The solvent was removed in vacuo by rotary evaporation and purified by flash chromatography (hexanes/EtOAc, 9:1) on silica gel to give 5.9 (75 mg, 83%) as a clear colorless oil. The spectroscopic data matched that in the literature.221 The enantiomeric excess was determined by SFC analysis (254 nm, 20 °C) tR 13.7 min (S); tR 14.5 min (R) [Chiralcel AS-H, CO2/i-PrOH  153 99:1, 100 bar, 2 mL/min] to be 92%. [α]D25 −18.6 (c 1.03, CHCl3); lit. [α]D20 –22.6 (c 1.8, CHCl3). 5.4.10 Synthesis of (S,E)-diethyl 2-(1,3-diphenylallyl)malonate (5.10) The representative procedure was followed using (E)-1,3-diphenylallyl acetate (70 mg, 0.28 mmol), diethylmalonate (93 mg, 0.58 mmol) and BSA (111 mg, 0.54 mmol) in CH2Cl2 (1.5 mL) for 48 h. Purified by flash column chromatography (hexanes/EtOAc, 9:1) to give 5.10 (80 mg, 81%). The enantiomeric excess was determined by SFC analysis (254 nm, 20 ºC) tR 22.2 min (S); tR 23.9 min (R) [Chiralcel AS-H, CO2, 100, 100 bar, 1.5 mL/min] to be 91%. [α]D25 −24.4 (c 1.32, CHCl3); lit. [α]D20 –17.2 (c 1.02, CHCl3) The spectroscopic data matched that in the literature.244 5.4.11 Synthesis of (S,E)-dibenzyl 2-(1,3-diphenylallyl)malonate (5.11)   The representative procedure was followed using 1,3-diphenyl-2-propenyl acetate (70 mg, 0.28 mmol), dibenzyl malonate (163 mg, 0.57 mmol) and BSA (111 mg, 0.54 mmol) in CH2Cl2 (1.5 mL) for 48 h. Purified by flash column chromatography (hexanes/EtOAc, 9:1) to give 5.11 (101 mg, 76%). The enantiomeric excess was determined by SFC analysis (254 nm, 20 ºC) tR 15.5 min (R); tR 20.1 min (S) [Chiralcel AD-H, CO2/i-PrOH, 92:8, 150 bar, 3 mL/min] to be 79%. [α]D25 −12.6 (c 1.3, CHCl3); lit. [α]D25 −4.5 (c 1.07, CHCl3) The spectroscopic data matched that in the literature.244 5.4.12 Synthesis (R,E)-dimethyl 2-(1,3diphenylallyl)-2-methylmalonate (5.12)  The representative procedure was followed using 1,3-diphenyl-2-propenyl acetate (60 mg, 0.24 mmol), dimethyl methyl malonate (96 mg, 0.66 mmol) and BSA (122 mg, 0.60 mmol) in CH2Cl2  154 (1.5 mL) for 48 h. Purified by flash column chromatography (hexanes/EtOAc, 85:15) to give 5.12 (59 mg, 73%). The enantiomeric excess was determined by SFC analysis (254 nm, 20 ºC) tR 10.8 min (R); tR 12.6 min (S) [Chiralcel AS-H, CO2/i-PrOH 97:3, 100 bar, 2mL/min] to be 91%. [α]D25 +22.5 (c 1.0, CHCl3), lit. [α]D +44.0 (c 0.4, CHCl3) The spectroscopic data matched that in the chemical literature.245 5.4.13 Synthesis (S,E)-3-(1,3-diphenylallyl)pentane-2,4-dione (5.13) The representative procedure was followed using 1,3-diphenyl-2-propenyl acetate (35 mg, 0.14 mmol), acetylacetone (56 mg, 0.56 mmol) and BSA (110 mg, 0.54 mmol) in CH2Cl2 (1.5 mL) for 48 h. Purified by flash column chromatography (hexanes/EtOAc, 9:1) to give 5.13 (16 mg, 40%). The enantiomeric excess was determined by SFC analysis (254 nm, 20 ºC) tR 25.1 min (S); tR 27.7 min (R) [Chiralcel OJ-H, CO2/i-PrOH, 99:1, 100 bar, 2 mL/min] to be 88%. [α]D27 +16.2 (c 3.5, EtOH); lit. [α]D23 +14.9 (c 1.8, EtOH) The spectroscopic data matched that in the chemical literature.246 5.4.14 Synthesis of (E)-dimethyl 2-(2-(benzyloxy)ethyl)-2-(1,3- diphenylallyl)malonate (5.14) The representative procedure was followed using 1,3-diphenyl-2-propenyl acetate (70 mg, 0.28 mmol), CH(CH2CH2CH2OBn)(CO2Me)2247 (155 mg, 0.58 mmol) and BSA (110 mg, 0.54 mmol) for 48 h. The product was purified by flash chromatography (hexanes/EtOAc/CH2Cl2, 85:7.5:7.5) to yield 5.14 (92 mg, 72%) as a colorless oil. The enantiomeric excess was determined by SFC analysis (254 nm, 20 ºC) tR 7.4 min (major); tR 8.1 min (minor) [Chiralcel AD-H, CO2/i-PrOH 92:8, 150 bar, 3mL/min] to be 89%.  155 1H NMR (400 MHz, CDCl3): δ 7.34–7.15 (m, 15H), 6.73 (dd, JHH = 16 Hz, JHH = 9 Hz, 1H), 6.33 (d, JHH = 16 Hz, 1H), 4.39 (s, 2H), 4.18 (d, JHH = 9 Hz, 1H), 3.70 (s, 3H), 3.58 (s, 3H), 3.59–3.44 (m, 2H), 2.25–2.10 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ 171.1, 170.8, 139.3, 138.4, 137.6, 132.5, 129.5, 129.4, 128.6, 128.5, 128.0, 127.8, 127.5, 126.6, 73.2, 67.0, 61.2, 54.7, 52.5, 52.4, 35.2; IR (neat): 3030, 2951, 2861, 1726, 1600, 1496, 1454, 1434, 1204; HRMS calcd for C29H30O5: 458.2093; Found: 458.2097; LRMS (EI): m/z [%]: 459, 458 [3, 10, M+], 367 [4, M+ − C7H7], 350 [5, M+ − C7H8O], 194, 193[19, 100, M+ − C14H17O5], 92, 91 [9, 97, C7H7+]; [α]D23 +49.4 (c 1.03, CHCl3). 5.4.15 Synthesis of (E)-dimethyl 2-(2-((tert-butyldimethylsilyl)oxy)ethyl)-2- (1,3-diphenylallyl)malonate (5.15) The representative procedure was followed using 1,3-diphenyl-2-propenyl acetate (70 mg, 0.28 mmol), CH(CH2CH2CH2OTBS)(CO2Me)2248 (168 mg, 0.58 mmol) and BSA (110 mg, 0.54 mmol) for 48 h. The product was purified by flash chromatography (hexanes/C6H6/EtOAc 5:5:1) to yield 5.15 (100 mg, 74%) as a colorless oil. The enantiomeric excess was determined by SFC analysis (254 nm, 20 ºC) tR 5.2 min (major); tR 5.8 min (minor) [Chiralcel AD-H, CO2/i- PrOH 96:4, 150 bar, 3mL/min] to be 89%. 1H NMR (400 MHz, CDCl3): δ 7.32–7.13 (m, 10H), 6.72 (dd, JHH = 16 Hz, JHH = 9 Hz, 1H), 6.33 (d, JHH = 16 Hz, 1H), 4.14 (d, JHH = 9 Hz, 1H), 3.69 (s, 3H), 3.69–3.65 (m, 1H), 3.63 (s, 3H), 3.58–3.50 (m, 1H), 2.15–1.96 (m, 2H), 0.82 (s, 9H), −0.03 (s, 3H), −0.04 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 171.0, 170.8, 139.4, 137.6, 132.5, 129.6, 129.4, 128.6, 128.6, 127.5, 126.6, 61.2, 60.1, 54.8, 52.4, 52.3, 37.9, 26.2, 18.6, -5.1; IR (thin film): 3030, 2953, 2857, 1729, 1601, 1496, 1435, 1253, 1205; HRMS calcd for C28H38O5Si: 482.2489; Found: 482.2488; LRMS  156 (EI): m/z [%]: 483, 482 [2,4, M+], 426, 425 [8, 26, M+ − t-Bu], 194, 193 [20, 100, M+ − C13H25O5Si], 116, 115 [8, 64, M+ − C6H15Si], 91 [21, C7H7+]; [α]D23 +47.8 (c 2.54, CHCl3). 5.4.16 Synthesis of (R,E)-dimethyl 2-allyl-2-(1,3-diphenylallyl)malonate (5.16) The representative procedure was followed using 1,3-diphenyl-2-propenyl acetate (70 mg, 0.28 mmol), CH(CH2CH=CH2)(CO2Me)2249 (100 mg, 0.58 mmol) and BSA (110 mg, 0.54 mmol) for 48 h. The product was purified by flash chromatography (hexanes/EtOAc/CH2Cl2, 8:1:1) to yield 5.16 as a colorless oil (87 mg, 85%). The enantiomeric excess was determined by SFC analysis (254 nm, 20 ºC) tR 17.1 min (major); tR 19.5 min (minor) [Chiralcel AD-H, CO2/i- PrOH 97:3, 100 bar, 2mL/min] to be 89%. 1H NMR (400 MHz, CDCl3): δ 7.37–7.17 (m, 10H), 6.76 (dd, JHH = 16 Hz, JHH = 9 Hz, 1H), 6.39 (d, JHH = 16 Hz, 1H), 5.85–5.73 (m, 1H), 5.07 (s, 1H), 5.04 (d, JHH = 7 Hz), 4.21 (d, JHH = 9 Hz), 3.75 (s, 3H), 3.67 (s, 3H), 2.68 (dd, JHH = 14 Hz, 7 Hz, 1H), 2.53 (dd, JHH = 14 Hz, 8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 170.8, 170.7, 139.6, 137.8, 133.6, 132.5, 129.8, 129.5, 128.7, 128.6, 127.5, 126.6, 118.7, 63.6, 54.1, 52.5, 39.6; IR (thin film): 3028, 2952, 1726, 1640, 1600, 1495, 1434, 1204, 1136 cm-1; HRMS for C23H24O4: 364.1675; Found: 364.1673; LRMS (EI): m/z [%]: 365, 364 [1, 5, M+], 323 [3, M+ − C3H5], 194, 193[17, 100, M+ − C8H11O4]; [α]D25 +30.8 (c 2.2, CHCl3). 5.4.17 Synthesis of (R,E)-dimethyl 2-(but-3-en-1-yl)-2- (1,3diphenylallyl)malonate (5.17)  The representative procedure was followed using 1,3-diphenyl-2-propenyl acetate (70 mg, 0.28 mmol), CH(CH2CH2CH=CH2)(CO2Me)2249 (108 mg, 0.58 mmol) and BSA (110 mg, 0.54 mmol)  157 for 48 h. The product was purified by flash chromatography (hexanes/EtOAc/CH2Cl2, 85:7.5:7.5) to yield 5.17 (101 mg, 95%) as a colorless oil. The enantiomeric excess was determined by SFC analysis (254 nm, 20 ºC) tR 15.1 min (R); tR 19.4 min (S) [Chiralcel AD-H, CO2/i-PrOH 97:3, 100 bar, 2mL/min] to be 92%.  1H NMR (400 MHz, CDCl3): δ 7.39–7.17 (m, 10H), 6.77 (dd, JHH = 16 Hz, JHH = 9 Hz, 1H), 6.41 (d, JHH = 16 Hz, 1H), 5.78–5.67 (m, 1H), 5.01–4.90 (m, 2H), 4.21 (d, JHH = 9 Hz, 1H), 3.76 (s, 3H), 3.70 (s, 3H), 2.17–1.83 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3): δ 171.2, 170.9, 139.7, 137.9, 137.8, 133.5, 129.8, 129.5, 128.7, 128.6, 127.5, 127.5, 126.6, 115.1, 63.0, 54.5, 52.3, 52.2, 34.5, 29.5; IR (thin film): 3028, 2951, 1725, 1642, 1600, 1496, 1450, 1434, 1201, 1135; HRMS for C24H26O4: 378.1831; Found: 378.1834; LRMS (EI): m/z [%]: 379, 378 [1, 4, M+], 277 (4, M+ − C5H9O2], 194, 193 [17, 100, M+ − C9H13O4]; [α]D25 +59.6 (c 0.56, CHCl3). 5.4.18 Synthesis of (R)-dimethyl 2-phenylcyclopent-3-ene-1,1-dicarboxylate (5.18) A solution of Grubbs II catalyst (5 mg, 0.006 mmol) and 5.16 (43 mg, 0.12 mmol) in CH2Cl2 (3 mL) was stirred for 16 h. The solution was directly purified by flash chromatography (hexanes/EtOAc, 95:5) to obtained 5.18 (26 mg, 85%) as a white solid. The enantiomeric excess was determined by SFC analysis (210 nm, 20 ºC) tR 7.1 min (R); tR 8.6 min (S) [Chiralcel OJ-H, CO2/i-PrOH, 97:3, 100 bar, 2 mL/min] to be 89%. mp 47−50; lit. 49–53; [α]D25 +311 (c 1.05, MeOH); lit. [α]D25 −377 (c 0.85, MeOH) (S)-enantiomer.250  158 5.4.19 Synthesis of (R)-dimethyl 2-phenylcyclohex-3-ene-1,1-dicarboxylate (5.19) A solution of Grubbs II catalyst (5 mg, 0.006 mmol) and 5.17 (45 mg, 0.12 mmol) in CH2Cl2 (3 mL) was stirred for 16 h. The solution was directly purified by flash chromatography (hexanes/EtOAc, 9:1) to obtained 5.19 (28mg, 87%) as a white solid. The enantiomeric excess was determined by SFC analysis (210 nm, 20 ºC) tR 7.6 min (S); tR 8.8 min (R) [Chiralcel OJ-H, CO2/i-PrOH, 97:3, 100 bar, 2 mL/min] to be 90%. mp 116-118 ºC; lit. 128-130 ºC;250 [α]D25 +336 (c 1.04, MeOH); lit. [α]D25 −477 (c 0.49, MeOH) (S) enantiomer.250 5.4.20 X-ray Crystallography  All single crystals were immersed in oil and mounted on a glass fiber. Data were collected on a Bruker X8 APEX diffractometer with graphite- monochromated Mo Kα radiation. All structures were solved by direct methods and subsequent Fourier difference techniques. All non-hydrogen atoms were refined anisotropically with hydrogen atoms being included in calculated positions but not refined. All data sets were corrected Lorentz and polarization effects. All calculations were performed using SHELXTL159 crystallographic software package from Bruker-AXS. Additional crystal data and details of the data collection and structure refinement are given in Table 5.2.  159  Table 5.2 Data Collection and Refinement Details for 5.2 and 5.8.a   5.2 5.8 formula C25H32Cl2NOPPd•CH2Cl2 C27H36Cl2N1O1P1Pd fw 655.71 598.84 cryst syst Triclinic Orthorhombic space group P1 P21,21,21 color Yellow Yellow a (Å) 8.428(1) 8.7130(2) b (Å) 8.919(1) 16.6610(4) c (Å) 9.803(2) 19.2860(5) α (deg) 93.261(1) 90.00 β (deg) 100.551(1) 90.00 γ (deg) 95.576(1) 90.00 V (Å3) 718.9(2) 2799.70(12) T (K) 173(2) 173(2) Z 1 4 µ(Mo Kα) (cm-1) 0.1093 0.0930 cryst size (mm3) 0.5 × 0.2 × 0.1 0.4 × 0.3 × 0.1 calcd density (Mg m-3) 1.525 1.421 2θ(max) (deg) 56.0 56.0 no. of reflns 21592 25502 no. of unique data 6376 6726 R(int) 0.0259 0.0312 refln/param ratio 20.3 18.63 R1b 0.0208; I > 2σ(I) 0.0264; I > 2σ(I) wR2 (all data)c 0.0463 0.0606 GOF 1.051 1.053 a Adapted with permission from Org. Lett., 2010, 12, 4667-4669. © 2010 American Chemical Society. b R1 = Σ||Fo|-|Fc||/Σ|Fo|. c wR2(F2[all data]) = {Σ[w(Fo2 – Fc2)2]/Σ[w(Fo2)2]}1/2  160 CHAPTER 6 Summary and Future Work 6.1 Summary   The work presented in this dissertation has expanded the use of phosphaalkene ligands in catalysis. The major contribution of this work was the design, the synthesis and the application of enantiomerically pure phosphaalkenes for transition metal catalysis. A smaller but important contribution was the incorporation of the smaller P-Mes group in phosphaalkenes as well as the application of P,N-chelate ligands in catalysis. The work presented has led to contributions to publications in general and subject specific peer-reviewed journals spanning the area of inorganic chemistry, organometallic chemistry and organic chemistry. The work published has also been presented in national and international conferences.   In Chapter 2, I demonstrated that a phosphaalkene Pd(II) complex bearing the smaller P- Mes substituent could be used in the Overman–Claisen rearrangement. This was also a rare example of a P,N-chelating phosphaalkene ligand used in catalysis. Linear allyl trichloroacetimidates containing aliphatic groups were good substrates for the Pd(II) catalyzed Overman–Claisen rearrangement using phosphaalkene complex 2.5. R1 O CCl3 HN 2.5 (5 mol %) CH2Cl2, 35 oC, 24 h R1 HN CCl3 O P C N Mes Pd Cl Cl 2.5 33-91% yield Scheme 6.1 Overman–Claisen Rearrangement with 2.5.   161 Chapter 3 outlined a modular route to enantiomerically pure phosphaalkene–oxazoline (PhAk–Ox). The synthetic route yielded a variety of different phosphaalkenes with different steric and electronic properties. The information gathered from these studies gave us more insight into the properties of the PhAk–Ox proligand set. Rare examples of a phosphaalkene containing a P-aryl ortho-position were also synthesized. Polymers of PhAk–Ox 3.25 were also obtained by thermal polymerization. R2 O R1 R1 O N H2N O ArP(SiMe3)Li R2 C P R1 R1 O NOH Ar PhAk–Ox (7 examples) Scheme 6.2 Synthesis of Enantiomerically Pure Phosphaalkene–Oxazoline.  In Chapter 4, I demonstrated that the PhAk–Ox proligands coordinate iridium(I) and rhodium(I). The data obtained from analysis of the complexes by X-ray crystallography and NMR spectroscopy are consistent with a change in geometry at P upon metal coordination. PhAk–Ox rhodium(I) complexes were applied in the allylic alkylation of branched allyl carbonates. Yields and enantioselectivities could not be optimized to synthetically acceptable levels but the investigation showed that the ligand structure could be modified and that these modifications had an effect on the enantioselectivities and yields.   162 [RhCl(cod)]2 AgOTf OTf R1 C O NP Ar Rh R1 C O NP Ar OCO2Et [Rh]OTf CH2CO2Me, base CHCO2Me enantioenriched Scheme 6.3 Synthesis of Rhodium Complexes and their Activity in Allylic Alkylation.  Chapter 5, I described the investigation of palladium catalyzed asymmetric allylic alkylation using PhAk–Ox proligands. The results obtained demonstrated that phosphaalkene ligands can give synthetically useful yields and enantioselectivities. The modular design in Chapter 3 permitted the addition of a gem-dimethyl group in the oxazoline core, which resulted in higher enantioselectivities. The use of the PhAk–Ox ligands in palladium catalyzed allylic alkylation reactions represents the highest enantioselectivities reported to date for phosphaalkene ligands. Importantly, this work represents an important proof that phosphaalkene ligands can be used in asymmetric catalysis and this paves the way for discovering reactions using these compounds. Ph Ph OAc base CH2Cl2 (20 ºC) Ph Ph CR(CO2Me)2 RHC(CO2Me)2+ Ph C P Mes O N Me Me Pd 5 mol % OTf 73-95% yield 79-92% ee Scheme 6.4 Palladium Catalyzed Allylic Alkylation Using a PhAk–Ox Ligand.  163 6.2 Future Work   Short-term future goals for this project are the synthesis of t-Bu oxazoline 6.1 (Figure 6.1). The observation of three conformations in the solid state molecular structure of 5.8 indicates that the presence of a t-Bu group might confer beneficial activity because all rotational conformation have the same steric properties. The incorporation of P-mono-ortho-aryl groups with either t-Bu oxazoline or t-Bu oxazoline equivalents might also be a beneficial modification. Resources into modifying the steric properties of the ligand at this point seem to be more valuable than modification of the electronic properties. C P Mes O N C P O N C P O N C P O N C P O N or or6.1 6.2 6.3 6.4 6.5 Figure 6.1 New Phosphaalkene Proligands.  Future work over a longer term is the synthesis of a larger library of PhAk–Ox proligands to allow facile investigation of ligand structure on the catalytic activity. Having a full set of systematic modifications could show very interesting trends, such as varying the P-aryl group systematically from Ph to Mes*. As well, generating this complete set also allows the investigation of the effect of sterics and electronic properties on the P=C bond and the ligand structure.  164 The investigation of the coordination chemistry of PhAk–Ox proligands with a wider range of metals would also give more insight into their bonding properties. More detailed spectroscopic investigation as well as computational methods, could give insight into a second generation of chiral phosphaalkene ligands. For example obtaining a solid state molecular structure of a PhAk–Ox palladium allyl complex could help identify improvements to the ligand structure in regards to allylic alkylation. A strategy to obtain a palladium allyl complex would be to generate the π-allyl complex with flanking phenyl groups [6.6] to impart the complex more crystallinity. Ph C P Mes O N Pd 6.6 X PhPh  Figure 6.2 Diphenyl Allyl Palladium PhAk–Ox Complex.  The following is a small sample of reactions that could be investigated for catalytic activity using the PhAk–Ox ligand. The palladium catalyzed asymmetric allylic alkylation of allyl alcohols (6A) is a logical extension of the work as well as it was previously performed with phosphaalkene ligands.133,134 Other reactions that have been performed with phosphaalkene P,N- ligands are the palladium and rhodium catalyzed conjugate addition of enones (6B).127,128 [3+2] cycloadditions of trimethylenemethane (6C)251,252 and the Stoltz modification of the Tsuji allylation (6D)253 would also be interesting palladium reactions to investigate the PhAk–Ox ligand since they are recently discovered enantioselective reactions with no general solution. Rhodium catalyzed isomerization is another reaction that is worth investigating (6E) since this reaction was shown to be effective with phosphaferrocene ligands.254,255 All these catalytic reactions could highlight and expand the use of phosphaalkene ligands.  165 OH + RNH2 Pd PhAk-Ox ! NHR 6A O + H2NCbz Pd or Rh PhAk-Ox ! O NHCbz 6B AcO TMS + R OH O O O R EWG Pd PhAk-Ox Pd PhAk-Ox ! ! R EWG 6C O 6D R ! O 6E Rh PhAk-Ox  Scheme 6.5 Catalytic Reactions to Investigate the Use of PhAk–Ox Proligands.   The proposed work illustrates a small sample of future directions that this project can take. There are many different areas of investigation involving phosphaalkene–oxazolines such as the modification of its structure, its coordination chemistry, its catalytic potential and its polymerization chemistry.  6.3 Concluding Remarks   This dissertation represents an initial investigation into the catalytic potential of the fascinating chemistry of phosphaalkene ligands. The overall goal of this project was to develop an enantiomerically pure ligand and discover new reactivity using this ligand. The work presented in this dissertation helped accomplished this goal by demonstrating the synthesis of chiral phosphaalkenes and by demonstrating their utility in asymmetric catalysis. Without a reliable route to access chiral phosphaalkenes their catalytic potential cannot be fully  166 investigated. Demonstrating the use of chiral phosphaalkene ligands in asymmetric catalysis serves as a proof of concept that these are interesting species for asymmetric catalysis. Increased visibility of this type of ligand can lead to a more active area of research, which will in turn generate new and interesting applications in the fields organic, organometallics and main group chemistry. 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