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Reactivity of rhodium-heteroatom bonds: from catalytic bond activation to new strategies for olefin functionalization van Rooy, Sara Emily 2007

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REACTIVITY OF RHODIUM-HETEROATOM BONDS: FROM CATALYTIC BOND ACTIVATION TO NEW STRATEGIES FOR OLEFIN FUNCTIONALIZATION by SARA EMILY VAN ROOY B.Sc., Dalhousie University, 2003  A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE  in  THE FACULTY OF GRADUATE STUDIES  (Chemistry)  THE UNIVERSITY OF BRITISH COLUMBIA October 2007 © Sara Emily Van Rooy, 2007  Abstract Rhodium complexes bearing multidentate nitrogen donor ligands were investigated for their ability to promote alkyne and olefin functionalization reactions. This thesis work is comprised of two projects in which rhodium-heteroatom reactivity is investigated: P-H bond activation reactions and olefin functionalizations via rhodaoxetane intermediates. [Tp*Rh(PPh3)2] [Tp* = hydrotris(3,5-dimethylpyrazolyl)borate] and [Tp*Rh(cod)]2 (cod = cyclooctadiene) were evaluated for their activity in alkyne hydrophosphinylation in comparison to known catalysts for this reaction. [Tp*Rh(PPh3)2] and [Tp*Rh(cod)]2 were both shown to effect hydrophosphinylation of 1-octyne with diphenylphosphine oxide with high regioselectivity but moderate yields in comparison with Wilkinson's catalyst [C1Rh(PPh3)3]. [Tp*Rh(PPh3)2] was further shown to effect hydrophosphinylation of a range of aromatic and aliphatic alkynes with diphenylphosphine oxide, in each case exclusively providing the E-linear vinylphosphine oxide product. 1 H and  31 P  NMR spectroscopy provided evidence that alkyne  hydrophosphinylation in the presence of pyrazolylborate rhodium complexes follows an analogous mechanism to that proposed for this reaction catalyzed by [C1Rh(PPh3)3] or [C1Rh(cod)]2. The 2-rhodaoxetane [(TPA)Rhmec2_,-4 u, 0-2-oxyethypr BPh4 - (TPA = tris[(2pyridal)methyl]amine) was investigated for its potential as an intermediate in proposed functionalization reactions of olefins. RTPA)Rh 111(K2 -C,0-2-oxyethyl)] + BPh4 - was prepared by two published methods with limited success. A third method involved the use of nitrous oxide to oxygenate [(1 2 -ethene)(K4 -TPA)Rh 1] + to RTPA)Rh 1110(-2 -C,0-2-  ii  oxyethyDr. Only a trace amount of [(TPA)Rh m oc2 -C,0-2-oxyethypr was observed in the 1 I-1 NMR spectrum of this reaction mixture. Initial test reactions of [(TPA)Rh ili oc2 _ C,0-2-oxyethypr combined with substrates (aniline, toluenesulfonamide, phenylboronic acid, or benzaldehyde) were inconclusive since the results were obscured by the impurity of the samples.  iii  Table of contents Abstract^  ii  Table of contents ^  iv  List of tables^  vii  List of figures ^  viii  List of schemes ^  ix  List of symbols and abbreviations ^  xi  Acknowledgements ^  Chapter 1 — Introduction ^  xiii 1  1.1 Metal-mediated olefin and alkyne functionalization ^ 1 1.2 Background of P-H bond activation reactions ^ 3 1.2.1 Scorpionate ligands ^ 3 1.2.2 Scorpionate complexes ^ 4 1.2.3 Isomerism of scorpionate complexes ^ 5 1.2.4 Reactivity of Tp RRII ILn complexes ^ 11 1.2.4.1 Stoichiometric reactions ^ 11 1.2.4.2 Catalytic reactions ^ 13 1.2.4.3 Mechanistic studies on hydrophosphinylation ^ 17 1.2.5 Conclusion ^ 19 1.3 Background of olefin functionalization reactions via rhodaoxetane intermediates ^ 19 1.3.1 Metallaoxetanes ^ 19 1.3.2 Oxidation of olefins ^ 20 1.3.3 Oxidation reactions with H202 as oxidant ^ 20 1.3.3.1 Rhodaoxetanes ^ 20 1.3.3.2 Mechanism of rhodaoxetane formation ^ 22 1.3.3.3 Reactivity of TPA-rhodaoxetane ^ 24 1.3.3.4 'N3'-rhodaoxetanes ^ 26 1.3.4 Oxidation reactions with 02 as oxidant ^ 28 1.3.4.1 The Wacker reaction ^ 28 1.3.4.2 Rhodadioxolane chemistry^ 31 1.3.5 Oxidation of organometallics with N20 ^ 33 1.3.6 Conclusion ^ 34  Chapter 2 — Hydrophosphinylation catalyzed by pyrazolylborate rhodium complexes ^  2.1 Introduction ^ 2.2 Research hypotheses and goals ^ iv  35 35 35  2.3 Results and discussion ^ 36 2.3.1 Catalytic hydrophosphinylation of alkynes ^ 36 2.3.1.1 Catalyst comparison ^ 36 2.3.1.2 [Tp*Rh(PPh3)2] catalyzed alkyne hydrophosphinylation — substrate scope ^ 39 2.3.1.3 Hydrophosphinylation in the absence of catalyst ^ 42 2.3.1.4 Background reaction of diphenylphosphine oxide with triphenylphosphine ^ 42 2.3.2 Crystallographic studies ^ 43 2.3.2.1 Effect of catalyst decomposition on hydrophosphinylation^ 46 2.3.3 Other P-H bond activation reactions ^ 47 2.3.3.1 Reactions of [TpRh(cod)] with diphenylphosphine ^ 48 2.3.3.2 Reactions of [TpRh(cod)] with dialkylphosphites ^ 48 2.3.4 Mechanism of P-H bond activation reactions ^ 53 2.4 Conclusions ^ 54 2.5 Experimental procedures ^ 55 2.5.1 General methods ^ 55 2.5.1.1 Preparation of [Tp*Rh(PPh3)2] III^ 56 2.5.1.2 Preparation of [Tp*Rh(cod)] IV ^ 56 2.5.1.3 Preparation of (E)-1-(diphenylphosphiny1)-1-octene 3 ^ 57 2.5.1.4 General small-scale hydrophosphinylation procedure ^ 57 2.5.1.5 Preparation of (E)-1-(diphenylphosphiny1)-3,3-dimethyl-l-butene 8 ^ 58 2.5.1.6 Preparation of (E)-1-(diphenylphosphiny1)-2-phenylethene 9 ^ 58 2.5.1.7 Preparation of (E)-1-(diphenylphosphiny1)-2-(4-methoxyphenypethene 10 ^ 59 2.5.1.8 Preparation of (E)-3-(diphenylphosphiny1)-3-hexene 11 ^ 59 2.5.1.9 Background reaction procedure ^ 60 2.5.1.10 Background reaction of diphenylphosphine oxide with triphenylphosphine ^ 61 2.5.1.11 Preparation of [TpRh(cod)] VIII ^ 61 2.5.1.12 Preparation of complex IX^ 62 2.5.1.13 Preparation of complex X ^ 62  Chapter 3 — Direct functionalization of olefins via 2-rhodaoxetanes ^ 63 3.1 Introduction ^ 63 3.2 Research goals ^ 64 3.2.1 Catalysis involving a 2-rhodaoxetane intermediate ^ 64 3.2.2 Regioselectivity of olefin functionalization reactions via 2-rhodaoxetanes ^ 66 3.2.3 Oxidation via TPA-rhodaoxetane ^ 68 3.2.4 Aminohydroxylation and arylhydroxylation via TPA-rhodaoxetane ^ 68 3.3 Results and discussion ^ 71 3.3.1 Preparation of TPA ^ 71 3.3.2 Preparation of [(1 2 -ethene)(K4 -TPA)Rh ir BPh4 - ^ 71 3.3.3 Preparation of TPA-rhodaoxetane ^ 72 3.3.3.1 Preparation of TPA-rhodaoxetane by hydrogen peroxide oxidation ^ 72  3.3.3.2 Background reaction of TPA with hydrogen peroxide ^ 73 3.3.3.3 Preparation of TPA-rhodaoxetane by nitrous oxide oxidation ^ 74 3.3.4 Reactions of TPA-rhodaoxetane ^ 74 3.3.4.1 Background reaction of benzaldehyde with hydrogen peroxide ^ 75 3.4 Summary ^ 76 3.5 Experimental procedures ^ 76 3.5.1 General methods ^ 76 3.5.1.1 Preparation of tris[(2-pyridyl)methyl]amine (TPA) 21 ^ 77 3.5.1.2 Preparation of [(1 2 -ethene)(K4 -TPA)Rh1 + BPh4 - XII ^ 78 3.5.1.3 Preparation of KTPA)Rh ili(K4 -C,0-oxyethyl)] + BPh4 XIII (by oxidation of [(i 2 -ethene)(K 4 -TPA)Rh ir BPh4" XII with H202) ^ 79 3.5.1.4 Preparation of RTPA)Rh 1i (K4 -C,0-oxyethyl)] ÷ BPh4 XIII (by oxidation of [(r1 2 -ethene)(K4 -TPA)Rh ir BP114 - XII with N20) ^ 79 3.5.1.5 Background reaction of TPA 21 with H202 ^ 80 3.5.1.6 Background reaction of benzaldehyde 22 with H202 ^ 80 3.5.1.7 Reaction of RTPA)Rh iliec4 -C,0-oxyethypr BPh4 - XIII with aniline 23 ^ 81 3.5.1.8 Reaction of [(TPA)Rh ili0c4 -C,0-oxyethypr BPh4 - XIII with toluenesulfonamide 24 ^ 81 3.5.1.9 Reaction of KTPA)Rh ili(K4 -C,0-oxyethyl)] + BPh4 - XIII with phenylboronic acid 25 ^ 82 3.5.1.10 Reaction of [(TPA)Rh 111(x4 -C,0-oxyethyl)] ÷ BP114 - XIII with benzaldehyde 22 ^ 83  Chapter 4 — Summary, conclusions and future work ^  84  4.1 Summary ^ 84 4.1.1 Hydrophosphinylation catalyzed by pyrazolylborate rhodium complexes ^ 84 4.1.2 Direct functionalization of olefins via 2-rhodaoxetanes ^ 85 4.2 Future Work ^ 85 4.2.1 P-H bond activation reactions catalyzed by pyrazolylborate rhodium Complexes^ 86 4.2.2 Functionalization reactions of olefins via 2-rhodaoxetanes ^ 86 4.2.2.1 Enantioselectivity of olefin functionalization reactions via 2-rhodaoxetanes ^ 86  References ^  88  Appendix I — NMR spectra ^  95  vi  List of tables Table 2-1 Catalyst comparison ^  37  Table 2-2 Alkyne substrate scope for hydrophosphinylation catalyzed by [Tp*Rh(PPh3) 2 ] ^  vii  40  List of figures Figure 1-1 Functionalized products derived from terminal olefins and alkynes ^ 2 Figure 1-2 General scorpionate ligand structure ^  3  Figure 1-3 Examples of K2 - and x3 -Tp RRhil, complexes ^  4  Figure 1-4 Conformational isomers of tris(pyrazolyl)borate rhodium complexes ^ 7 Figure 1-5 Polypyrazolylborate rhodium complexes with varied substituents at positions 3 and 5 on the pyrazolyl rings ^  9  Figure 1-6 Oxidative addition products of ethylpropiolate and benzaldehyde to [Tp*Rh(PPh3)2] ^  13  Figure 1-7 Products of P-H bond activation reactions ^  16  Figure 1-8 General 2-metallaoxetane structure ^  19  Figure 1-9 TPA-rhodaoxetane ^  21  Figure 1-10 Tris[(2-pyridal)methyl]amine (TPA) ^  22  Figure 1-11 Structure of 'N3'-rhodaoxetanes ^  26  Figure 2-1 Molecular structure of complex VI ^  44  Figure 2-2 Molecular structure of complex VII ^  45  Figure 2-3 Structures of proposed complexes IX and X ^  52  Figure 2-4 Structure of compound VI ^  52  Figure 3-1 RTPA)Rh ill(K2 -C,0-2-oxyethyl)] + BPh4 - XIII ^  64  viii  List of schemes Scheme 1-1 Isomerism of a tris(pyrazolyl)borate rhodium complex ^ 5 Scheme 1-2 Orthometalation of [Tp*Rh(PPh3)2] ^  13  Scheme 1-3 Alkyne hydrothiolation ^  14  Scheme 1-4 Alkyne hydrophosphinylation ^  16  Scheme 1-5 Horner-Wadsworth-Emmons olefination reaction ^ 17 Scheme 1-6 Mechanism of hydrophosphinylation catalyzed by either [C1Rh(cod)]2 or C1Rh(PPh3)3, as proposed by Han ^  18  Scheme 1-7 Preparation of the first isolable rhodaoxetane ^ 20 Scheme 1-8 Preparation of RTPA)Rh 111 ((2 -C,0-2-oxyethyl)] + , TPA-rhodaoxetane ^ 22 Scheme 1-9 Mechanism of oxidation of RTPA)Rhkethene)] by H202 ^ 23 Scheme 1-10 Cis and trans approaches of H202 attack ^  24  Scheme 1-11 Reactivity of TPA-rhodaoxetane ^  25  Scheme 1-12 Acetonitrile insertion of TPA-rhodaoxetane and subsequent rearrangements ^  26  Scheme 1-13 Theoretical catalysis of acetaldehyde from ethene via 'N3'-rhodaoxetane ^ 27 Scheme 1-14 Formation of a formylmethyl-hydroxide rhodium complex ^ 28 Scheme 1-15 Catalytic oxygenation reactions ^  28  Scheme 1-16 The Wacker reaction ^  29  Scheme 1-17 Wacker-Tsuji oxidation ^  29  Scheme 1-18 Mechanism of the Wacker reaction ^  31  Scheme 1-19 Preparation of a 3-rhoda-1,2-dioxolane ^  32  Scheme 1-20 Rearrangement of 3-rhoda-1,2-dioxolanes ^  33  ix  Scheme 1-21 Oxygen insertion into metal complexes by N 2 O^ 33 Scheme 1-22 Oxygen insertion into an organonickel complex by N2O ^ 34 Scheme 2-1 Synthesis of complex VI ^  44  Scheme 2-2 Synthesis of complex VII ^  45  Scheme 2-3 Isomerism of [HRhf[P(OPH)20]2H}2] ^  51  Scheme 2-4 Tautomerism of hydrogen phosphonates ^  51  Scheme 2-5 Generalized mechanism of P-H activation reactions catalyzed by rhodium complexes ^  54  Scheme 3-1 Reactivity of 2-metallaoxetanes ^  63  Scheme 3-2 Oxidation, aminohydroxylation and arylhydroxylation of ethylene, via a 2-metallaoxetane intermediate ^  64  Scheme 3-3 Proposed catalytic cycles involving a 2-rhodaoxetane intermediate ^ 65 Scheme 3-4 Possible regioisomers of 2-rhodaoxetanes formed from a mono-substituted olefin ^  67  Scheme 3-5 Possible outcomes of the proposed functionalization reactions with monosubstituted olefins ^  67  Scheme 3-6 Mechanisms for the reactions of TPA-rhodaoxetane XIII with acetone, amines and organometallics ^ Scheme 3-7 Rh-catalyzed 1,4-addition reaction ^  70 70  Scheme 4-1 Possible outcomes of the proposed functionalization reactions with either 1,1- or 1,2-disubstituted olefins ^  87  List of symbols and abbreviations A^angstroms (10 0 meters) ° or deg^degrees degrees Celsius 8^chemical shift microliter v^frequency acac^acetylacetonato Ar^aryl Bp*^dihydrobis(3,5-dimethylpyrazolyl)borate br^broad Bu^butyl Bz^benzyl Bzbpa^N-benzyl-N,N-di(pyridylmethyl)amine calcd^calculated cm^centimeters cod^cyclooctadiene COSY^correlation spectroscopy Cp^cyclopentadienyl Cp*^pentamethylcyclopentadienyl D, d^deuterium 2D^two-dimensional d^doublet DCE^1,2-dichloroethane DCM^dichloromethane dd^doublet of doublets ddd^doublet of double doublets ddq^doublet of double quartets DFT^density functional theory E^entgegen EI^electron impact Eq.^equation equiv.^equivalents Et^ethyl g^gram GC^gas chromatography  GCMS^gas chromatography-mass spectroscopy h^hours, Planck's constant HRMS^high resolution mass spectroscopy Hz^hertz i-Pr^isopropyl IR^infrared J^coupling constant kcal^kilocalorie L^liter, ligand M^molar (mol L -1 ) m^multiplet Me^methyl mg^milligram MHz^mega hertz min^minutes mL^milliliter mmol^millimole mol^mole m/z^mass/charge n^normal nbd^norbornadienyl NMR^nuclear magnetic resonance Ph^phenyl ppm^parts per million pz^pyrazolyl pz*^3,5-dimethylpyrazoly1 q^quartet rt^room temperature s^singlet t^tertiary t^triplet TfO^trifluoromethanesulfonate THE^tetrahydrofuran TLC^thin layer chromatography Tp^hydrotris(pyrazolyl)borate Tp*^hydrotris(3,5-dimethylpyrazolyl)borate TPA^tris[(2-pyridyl)methyl]amine UV^ultra violet VT^variable temperature Z^zusammen  Acknowledgements Many people have been generous with their expertise, time, advice and encouragement. I could not have completed this project without their support, for which I am truly grateful. First of all, I would like to thank my supervisor, Dr. Jennifer A. Love. Her ideas and her wealth of knowledge are ever-inspiring. She is a kind, patient and supportive leader to our group and has been a mentor to me throughout my graduate studies. It has been a great experience participating in the launch of her research program. I would like to thank the members of the Love research group: Paul Bichler, Jeffery Bird, Heather Buckley, Changsheng Cao, Alex Dauth, Lauren Fraser, Bal Kang, Anthony Sabarre, Shiva Shoai, Alex Sun, Tongen Wang and Jun Yang. They have provided valuable feedback, encouragement and camaraderie, which has greatly enhanced my experience at UBC. I have really appreciated all the advice and assistance from Lauren Fraser, our group's first graduate (and a great friend). I especially want to thank Shiva Shoai for being such a great friend and being the person above all who really welcomed me to the UBC Chemistry crowd and to Vancouver in general. Thank you to all of the UBC Chemistry department's faculty, support staff and administrative staff. In particular, the NMR staff have been an invaluable resource. Thanks as well to the UBC librarians, especially Kevin Lindstrom. Many thanks go to my neighbors, friends, and family, who have given me so much support: Caroline, Jason and Milan Crowe (and Papi); Tabea and Paulina Dauth; Sandy and Micha Hamouz; Claire and Mila Plumb; Amanda and Larry Richer; Emily Simpson and Robyn Williams; Brian Rempel and Dana Kotovych; Shiva Shoai and Rob  Thomson; Lauren Fraser; Kim Van Rooy; and Joshua Knauer. Hundreds of hours of entertainment were provided to my daughter Maggie, enabling me to spend precious time writing this thesis. Thanks to my long-distance family and friends who have provided lots of support and encouragement over the phone and by email. I especially want to mention my parents, Kim and Bill, my sister Naomi, and my best friend Tara. Most importantly I want to thank my life partner, Joshua Knauer, and my daughter Maggie. I dedicate this work to you both.  xiv  1 Introduction 1.1 Metal-mediated olefin and alkyne functionalization Simple olefins and alkynes are inexpensive and readily available as products of the petroleum industry. The development of reactions that transform simple olefins and alkynes into functionalized products is of fundamental importance to synthetic chemistry. The most straightforward approach for preparing these functionalized products involves the introduction of functional groups directly to unactivated carbon-carbon 7r-bonds. Metal catalysts have been used to achieve this goal in research laboratories and in industry. 1-11 Olefins and alkynes can be converted to ketones, aldehydes, and many other products, which can be further functionalized to a broad array of useful small molecules to be used as building blocks in synthesis. Figure 1-1 shows a variety of available products from functionalization reactions of terminal olefins or alkynes. 9-12  1  ^  hydration^R OH  R"*  HO OH dihydroxylation^ ^/ )  R  epoxidation  0  R  hydroalkoxylation^  ROR' 0^0  vinylic oxidation^Rj-L  H R 0^0  hydroformylation  R  )( 1-1 R  HO OH  allylic oxidation  hydrocarboxylation or hydroesterification  R  hydroamination  R  COOR'  0  R COOR'  NR 1 R2 )^NR1R2  NR 1 R2 oxidative amination^R  ^  NR 1 R 2  R  0^0 hydration^IR)^ 0  R —  Rj-L  H  carbonylation^RACOOR'^COOR' R'■ NR'^R'^ N^ N 1R)-^RNR' hydroamination^ R R" I ' H^ R SR' 1'SR'^ R^SR' .0 R ^.Fr.,0  hydrothiolation^R te hydrophosphinylation R  e,p'  R'2^R.2  R^  - ' O'PR 2  Figure 1 1 Functionalized products derived from terminal olefins and alkynes -  The study of these known processes as well as the development of new coupling reactions remains a highly active research area. The development of new, catalytic  2  methods for the selective functionalization of olefins and alkynes is a focus for the Love group. The approach taken in this thesis work involves studying the reactivity of Rh-P and Rh-0 bonds for two classes of carbon-carbon n-bond functionalization reactions: P-H bond activation reactions and olefin functionalizations via rhodaoxetane intermediates. These reaction classes both involve rhodium complexes with multidentate nitrogen donor ligands; however, they are mechanistically distinct. The research presented in this thesis on Rh-P and Rh-0 reactivity will thus be addressed in two separate chapters. This chapter provides the background information for these two subprojects.  1.2 Background of P-H bond activation reactions 1.2.1 Scorpionate ligands The hydrotris(pyrazolyl)borate anion (Tp) and its use in coordination chemistry were first introduced by Trofimenko in 1966. 13 Since that time Tp and many of its derivatives (Tp R, R = H, alkyl, aryl, substituted aryl, halide, etc.) have been utilized as ligands for numerous coordination complexes. 14 Tp R, shown in Figure 1-2, is an example of a scorpionate ligand; it is a tripodal donor where two of the binding groups are firmly bound to the metal center and the third binding group is more labile, like the claws and stinger of a scorpion. The stinger can be identical to the claws (i.e. homoscorpionate) or different (i.e. heteroscorpionate). Many other scorpionate ligand derivatives are known with various substituents at the 3, 4, and 5 positions on the pyrazolyl groups. 15  Tp : R = R' = H Tp*: R = R' = Me Tp me : R = Me, R' = H  Figure 1 2 General scorpionate ligand structure -  3  1.2.2 Scorpionate complexes Most Tp R-metal complexes are either octahedral, trigonal bipyramidal or square planar in geometry. The octahedral and trigonal bipyramidal complexes have Tp R bound facially (i.e. K 3 ) to the metal whereas in the square planar complexes, the Tp R ligand binds with only its pincers (i.e. K 2 ), and the stinger is uncoordinated. Some examples of K2 - and K3 -Tp RRh1L„ complexes are shown in Figure 1-3.  —N  PPh3 N^ ,B H 1■1^PPh3  ,,,B,^RH 11^N,NI  [K 2 -Tp*Rh(PPh3)2]  [K 2 -Tp*Rh(cod)]  NN"N',.  NON H—B'  N Rh....  k  F21-1  4  -  PEt3 [K 3 -Tp me Rh(nbd)]  [K 3 -Tp *Rh(C2H4)(PEt3)]  Figure 1 3 Examples of K2 - and K 3 -Tp RRIIILn complexes -  The Tp ligand has been compared to the cyclopentadienyl ligand (Cp) since they are isoelectronic structures. Both Tp and Cp are monoanionic and are 6-electron donors when facially bound to a metal. However, Tp is far bulkier than Cp (cone angle of 211° versus 140 0) 16 and Tp is a hard N donor, whereas Cp is soft. In solution, Tp R-metal complexes usually exhibit rapid exchange between coordinated and uncoordinated pyrazolyl groups, observed in their nuclear magnetic resonance (NMR) spectra as an averaging of these 1 1-1 signals. 17 This lability makes square planar Tp R-metal complexes ideal as catalyst candidates since the stinger group can assist in converting the complex  4  from square planar to octahedral, then readily fall off again as the complex reverts back to the active catalyst. Scorpionate complexes are known for many elements, including most of those in groups 1 to 13, phosphorus, most lanthanides, and some actinides. 14 Reactivity of Tp R-metal complexes includes photochemical and thermal stoichiometric transformations as well as catalytic reactions. 18  1.2.3 Isomerism of scorpionate complexes The lability of the stinger group in Tp R-metal complexes has been demonstrated in the NMR spectroscopy of these complexes. Chauby et al. obtained crystal structures of complexes [Tp*Rh(CN-neopenty1)2] (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate) and [Tp'Rh(nbd)2] (Tp' = HB(3-Mepz)3) that show ic2 - and K3 -binding, respectively. 17 However, in solution both of these complexes show an equivalence of their three pyrazolyl groups in their 1 H NMR spectra, suggesting a rapid exchange between pyrazolyl groups, as shown for a general TpRhI complex in Scheme 1-1.  11\ 13  N  .N—N.„.L N N  ;;  —  N  ^  Rh-L ^L  Scheme 1-1 Isomerism of a tris(pyrazolyl)borate rhodium complex Jones and Hessel report that complexes of the type Tp*Rh(CNR)2 (R = neopentyl, 2,6-xylyl, methyl) show fluxional behavior in their IR spectra as well as 1 H and 13 C NMR spectra. 19 They suggest that NMR spectroscopic evidence showing equivalence of the pyrazolyl signals is not sufficient to conclude that isomerism of ic 2 and K3 forms is occurring. An alternative explanation could be that the ic 3 isomer is the dominant form in solution and the observed equivalence of the pyrazolyl groups is due to rotation about the  5  Rh-B axis that is rapid on the NMR timescale. A comparison of the IR spectroscopy of these complexes in the solid state and in solution shows the isonitrile stretching frequencies to be identical. They also report that in the PhD dissertation of Ghosh, the IR spectra of an isomeric mixture of x 2 - and K3 -Tp*Rh(C0)2 in CH2C12 solution was reported to have a 20-30 cm-1 difference in the carbonyl stretching frequencies which corresponds to a similar difference of 20-30 cm -1 in the carbonyl stretching frequencies of solutions of K 3 -Tp*Rh(C0)2 and x2 -(H2B(pz*)2Rh(C0)2. 2° '21 These findings support the hypothesis that these complexes remain as the K-2 -isomer in solution but with a rapid interchange of pyrazolyl groups via isomerism to the K 3 form. Bucher et al. details the fluxional behavior of complexes of the type TpRh(LL) (LL = 2CO, cod, nbd). 22 The substituents at the 3 and 5 positions on the pyrazolyl groups affected interconversion rates between ic 2 and ic3 forms such that the larger substituents disfavored the formation of the K 3 isomer. Other factors that were shown to affect the rate of isomerism included the ancillary ligands on rhodium as well as solvent polarity. Energies of activation for the isomerism of K2 and ic3 forms of Tp RRhLn complexes have been estimated based on their observed coalescence temperatures in variable-temperature 1 H NMR studies. 23 For [TpRh(C2H4)(PPh3)], = 60 kJ/mol. 24 For [Tp*Rh(CO)(PMe 3 )], AG ,a,,3 = 63 kEmol. 17 Scorpionate rhodium complexes of the type [Tp RRIIILL] can adopt up to four conformational isomers, as evidenced by IR and NMR spectroscopy as well as X-ray crystallography of a number complexes of this type. 25 These four isomers are shown in Figure 1-4. 26 ' 27  6  H, B 7  \ A  ,^Rh's  H. B .N.  N  I  „,L  I  ^  C  ^  D  Figure 1-4 Conformational isomers of tris(pyrazolyl)borate rhodium complexes  Connelly et al. reported solution and solid state structural data for [Tp*Rh(PPh3)2]. 28 Their study included analysis of room temperature and -80 °C NMR spectroscopic experiments ( 1 H NMR and 31 P { 1 H} in CD2C12), IR spectroscopic data, and the crystal structure of this complex. The X-ray crystal structure of [Tp*Rh(PPh3)2] shows K2 -coordination of Tp* to rhodium, as in conformation B. The solid state IR spectrum shows a B-H stretching frequency of 2467 cm 1, which also indicates K 2 -binding of Tp*. At room temperature the 1 H and 31 P { 1 }1} NMR spectroscopic evidence suggests that [Tp*Rh(PPh3)2] exists in the K 2 conformation in solution, with free rotation about the B-N bond of the uncoordinated pyrazole group. The 1 H NMR signals for the pyrazole rings appear in a 2:1 ratio, indicating the equivalence of two of these groups. As well, both phosphines are equivalent in the 31 P { 1 H} NMR spectrum at this temperature. At -80 °C, three sets of pyrazole ring signals are seen in the 1 H NMR spectrum and the phosphines are no longer equivalent in the 31 P { 1 H} NMR spectrum. They suggest that the low temperature inequivalence of these signals is due to restricted rotation of the unbound pyrazolyl ring. Connelly et al. also studied [TpRh(PPh3)2]. They do not report a solid state structure for this complex; however, IR spectroscopy of the solid complex shows two BH stretching frequencies that are both indicative of K2 -coordination of Tp (2414 and 2394  7  cm-1 ). 28 They attribute the two signals to the presence of both  K2  conformers, A and B. 1 1-1  NMR spectroscopy was not informative for this complex since even at low temperature, the spectra could not be resolved. The room temperature 31 P { 1 1-1} NMR shows a broad doublet that splits into two signals as the temperature lowers to -80 °C. For this complex, they attribute the two signals to the presence of the two conformers, A and B, in approximately equal abundance. The two signals could not be attributed to a single isomer with inequivalent phosphines since the signals would then have appeared as doublets of doublets. Fraser et al. compared a series of pyrazolylborate rhodium complexes for their solid state and solution structures as well as their catalytic activity in alkyne hydrothiolation reactions. 26 '27 Five complexes were examined in this study: [Tp RRh(PPh3)2], where Tp R = HBR'3 (R' = 3,5-dimethylpyrazolyl (1), pyrazolyl (3), 3phenylpyrazolyl (4), or 3-phenyl-5-methylpyrazolyl (5)) and [Bp RRh(PPh3)2] (Bp R = H2BR'2, R' = 3,5-dimethylpyrazolyl) (2). These complexes are shown in Figure 1-5. These complexes were chosen to determine what effect varying the size and number of substituents on the pyrazolyl groups might have on their solution geometry and also what impact this may have on their catalytic activity in alkyne hydrothiolation reactions.  8  ^  / I —N PPh 3 \^.,S0 PPh3^H•^ 1•1^so^ Rh Rfi N,N■ H^N—^N, ■PPh3  1 [Tp*Rh(PPh 3 ) 2 ] Ph  ^  Ph  ^  —N^PPh3 •• N  IRfi■  PPh3  Ph  2 [Bp*Rh(PPh 3 )2 ]  ^  PPh 3  \I^  ^  3 [TpRh(PPh3)2]  Ph  ^N I  N N1^ B^Rh' H Rh ^ N-  I^  PPh3  Ph  Ph 4 [Tp Ph Rh(PPh 3 ) 2 ]  N— 1Rh■ N  PPh3  \  ^  / I —N^PPh 3 N^0^  5 [Tp Ph,me Rh(PPh 3 ) 2 ]  Figure 1-5 Polypyrazolylborate rhodium complexes with varied substituents at positions  3 and 5 on the pyrazolyl rings  The X-ray crystal structures of complexes 2-5 were characterized26 '27 and compared to the reported structure of [Tp*Rh(PPh3)2]. 28 In the solid state, all five complexes show K2 -coordination. IR spectroscopic evidence for complexes 1 and 3-5 also corresponds to K 2 -coordination. 26-28 Specifically, complexes 1 and 5 have substituents at the 3- and 5-positions on their pyrazolyl groups and they exist in the B form with the uncoordinated pyrazolyl group pseudo parallel to the Rh square plane. Complexes 3 and 4 have no substituents at the 5-position and they exist in the A form with the  uncoordinated pyrazolyl group perpendicular to the Rh square plane. For the room temperature I I-I and 31 P { 1 I-1} NMR spectroscopic studies on [Tp*Rh(PPh3 )2 ] 1, Fraser et al. obtain results that are consistent with those reported by Connelly et al. showing equivalence of the signals for two of the pyrazolyl rings and the phosphines. 26-28 At -80 °C, the results of these two studies differ. Fraser et al. do not see inequivalence of the pyrazolyl groups or phosphines. Presumably, rotation of the free  9  pyrazolyl ring about the B-N bond is not sufficiently slow for the NMR time-scale of their study. Between the two studies, the evidence suggests that [Tp*Rh(PPh 3 )2 ] exists in solution with K2 -coordination over a range of temperatures. The 1 H and 31 P { 1 H} NMR spectroscopic data for [Tp PhRh(PPh3)2] 4 at room temperature and -85 °C shows equivalence of the signals for the pyrazolyl rings and phosphines, indicating  K2  coordination in solution. 26 '27  For [Tp Ph'meRh(PPh3 ) 2 ] 5, the room temperature 1 H NMR spectroscopic signals for the pyrazolyl rings are equivalent. At -85 °C these signals become inequivalent, suggesting restricted rotation of the free pyrazolyl ring about the B-N bond. The room temperature 31 P { 1 H} NMR spectrum shows a 1:5 ratio of phosphine signals at 6 48.12 (d, JRh_p =  182 Hz) and 6 43.44-39.33 (m), respectively. A variable temperature  31 P { 1 H}  NMR spectroscopy experiment was performed for this complex. As the temperature decreased, the doublet signal disappeared and the multiplet signal resolved into two doublets of doublets (6 42.60, dd,  JRh_p =  178 Hz, Jpp' = 50 Hz; 6 39.42, dd, JRh_p,  =  172  Hz, Jpp' = 51 Hz). The authors suggest that there are two species present at room temperature. At lower temperatures it may be that one isomer predominates the solution. Since coalescence of the phosphine signals was not observed, the authors suggest it is more likely that both are present in the low temperature solution but that the minor isomer is not seen due to broadening of the peaks from restricted rotation of the free pyrazolyl ring. As the temperature was raised, the doublet peak remained the same but the multiplet coalesced into a doublet. This observation is consistent with the free rotation of the unbound pyrazolyl group in the major isomer at higher temperatures but restricted rotation just under room temperature. The two species could be conformational isomers  10  A and B, or they could be regioisomers resulting from rearrangement by a 1,2-borotropic shift. Complexes 1 5 were compared for their catalytic activity and selectivity in -  hydrothiolation reactions involving a range of alkynes and thiols with varying levels of steric bulk and functionality. Complexes with substituents at both the 3 and 5 positions on the pyrazolyl groups (1 and 5) provided the best yields and selectivities for these reactions. Complexes 1 and 5 also happened to exist in form B in the solid state and maintained K2 -coordination in solution, showing evidence that restricted rotation of the free pyrazolyl group was occurring at lower temperatures. These results suggest that an ability to adopt K 3 -coordination in solution greatly enhances catalytic activity and selectivity for pyrazolylborate rhodium complexes in alkyne hydrothiolation reactions.  1.2.4 Reactivity of Tp RRhiL n complexes Since Tp R ligands are hard N donors, the reactivity of Tp RRII II., complexes for oxidative addition reactions is thought to be enhanced by the relative stability that Tp R affords to the Rh" product. This feature has made Tp RRhLn complexes appealing candidates for their potential use in catalytic reactions. To date there are a number of stoichiometric and catalytic reactions known for these complexes and potential for much more investigation.  1.2.4.1 Stoichiometric reactions The complex [Tp*Rh(C0) 2 ] has been shown to photochemically activate C-H bonds in aromatic and saturated hydrocarbons at room temperature.  29  Lian et al. later  observed a reactive intermediate for this reaction in their femtosecond time-resolved IR spectroscopy study. 3° The observed reactive intermediate is a solvated monocarbonyl  11  complex. The thermal activation of C-H bonds by [Tp*Rh(CO)2] in benzene at 140 °C was achieved but with low yield and many decomposition products. 31 An attempt to improve the yield involved tailoring the Tp*RhL. complex with more labile ligands. Complexes of the type [Tp*Rh(C0)(1 2 -alkene)], where alkenes include ethylene, propylene and cyclooctene were prepared. These complexes were then used to thermally activate benzene in the range of 70 —100 °C, forming [Tp*Rh(H)(CO)(Ph)] in 90% yield. Hessel and Jones heated [Tp*Rh(CN-neopentyl)(ri 2 -PhN=C=N-neopenty1)] in benzene to 100 °C and achieved C-H bond activation of benzene to form [Tp*Rh(H)(Ph)(CN-neopenty1)]. 32 The same treatment of the analogous Cp* complex yielded no C-H activation product. They were also able to achieve reductive elimination of benzene by the thermolysis of [Tp*Rh(H)(Ph)(CN-neopenty1)]. 33 Circu et al. prepared [Tp*Rh(PPh 3 )2 ] and [Tp*Rh{P(4-C6H4F)3}2]. Reaction of these two complexes with both phenylacetylene and para-nitrobenzaldehyde yielded C-H activation products. Reaction of the same two complexes with triphenyltin hydride also yielded the Sn-H activation product. 34 Our group recently found that when [Tp*Rh(PPh 3 )2] is left in 1,2-dichloroethane (DCE) or tetrahydrofuran (THF), orthometalation of one of the phenyl rings on PPh3 occurs. 35 This reaction is shown in Scheme 1-2. This does not occur in toluene and the reaction is suppressed in a 1:1 mixture of DCE and toluene. The oxidative addition of both ethylpropiolate and benzaldehyde to [Tp*Rh(PPh3) 2 ] occurs with a loss of PPh3, consistent with the findings of Circu et al. These products are shown in Figure 1-6. If left in DCE or THF, these oxidative addition products undergo orthometalation of a  12  phosphine phenyl group to yield the same product as in the previous example, with loss of ethylpropiolate or benzaldehyde. —N N HB  N^N  ,^,PPh 3 N / Rh N^PPh3  DCE rt, 12 h (73%)  Scheme 1 2 Orthometalation of [Tp*Rh(PPh3)2] -  HB ,,,PPh3 ^  Fl  I^ I CO 2 Et Figure 1 6 Oxidative addition products of ethylpropiolate and benzaldehyde to -  [Tp*Rh(PPh3)2]  Circu et al. report that reaction of [Tp*Rh(PPh 3 ) 2 ] with C6F5SH gives the stoichiometric S-H activation product and the Tp* ligand fragments to give a 3,5dimethylpyrazolyl (pz*) ligand. 36 They also report that Ph 3 SiH in CH2C12 reacts with [Tp*Rh(PPh3)2], fragmenting Tp* and CH2C12 to give pz*, Cl, and H ligands. Reaction of [Tp*Rh(PPh3 ) 2 ] with HgC12 leads to the complete loss of Tp* ligand and the formation of a Hg-bridged dirhodium complex with PPh3 and Cl ligands. 1.2.4.2 Catalytic reactions  Stereoregular polymerization of phenylacetylenes was achieved using [Tp*Rh(cod)], [Tp Ph2Rh(cod)] and [Tp i-Pr2 Rh(cod)]. 37 Catalysis was achieved using 1 mol% catalyst in CH2C12 solvent at 40 °C for 24 h and only worked for para substituted 13  phenylacetylenes. Generally yields were higher with bulkier Tp R ligands. The regioselective, homogeneous hydrogenation of quinoline was achieved using [TpRh(cod)] prepared in situ. 38 [TpRh(cod)] was compared to related complexes of other metal centers including Ir and Ru. The catalytically active species is presumed to be [TpRh(quinoline)2]. Trujillo reported the results of a preliminary study in which the dimerization of terminal alkynes was achieved using [Tp*Rh(C2H4)(PEt3)] as a catalyst. In the same doctoral thesis work, [Tp*Rh(C2H4)2] was shown to catalyze the hydrosilylation of ethylene. 39 Hydrothiolation is the addition of a thiol S-H bond to a double or triple C-C bond, as shown in Scheme 1-3. 4°41 The products can be branched (B or C) 4°42 or linear (A). 4345  The third product type (C) forms from a double bond isomerization that occurs either  before or after reductive elimination of the branched internal vinyl sulfide product (B) from the metal catalyst. 4°43 The regioselectivity of the reaction is highly tunable in that product distribution is strongly affected by the choice of catalyst and conditions. For instance, Wilkinson's catalyst provides stereoselective and regioselective addition of arylthiols to alkynes such that only the E-linear vinyl sulfide forms. 4° RSR' R'SH  [MLn]  or SR'  double or triple bond  A (E or Z)  ^  C  Scheme 1 3 Alkyne hydrothiolation -  The mechanism of hydrothiolation using Wilkinson's catalyst is believed to 14  proceed via trans-RhH(SPh)Cl(PPh 3 ) 2 as the active catalyst. 4° '46 The alkyne is thought to insert stereoselectively into the Rh-H bond, forming a trans-vinylrhodium intermediate, which then reductively eliminates the linear adduct in the presence of thiol. Pd and Ni catalysts typically provide the branched products (B and C) when used with aryl thiols but no analogous reaction occurs with alkyl thiols. 4° '42 In our lab, catalytic hydrothiolation of alkyl and aryl thiols was achieved using [Tp*Rh(PPh3)2] catalyst with a range of alkynes in high yield and regioselectivity for the branched product.  41  It was  thought that rhodium complexes bearing the Tp* ligand might be able to effect catalytic alkyl hydrothiolation because they have shown an ability to promote stoichiometric and catalytic bond activation. 18,36 ' 39,47 Hydrothiolation using [Tp*Rh(PPh3)2] with alkyl thiols forms the branched product exclusively and with aryl thiols a mixture of branched and linear products forms. In related work our group has also found that Wilkinson's catalyst, in contrast to published accounts which are limited to aryl thiols, 4° affords the E-linear isomer preferentially when used with alkyl thiols. The activation of phosphorus-hydrogen bonds by metals can lead to many highly useful compounds containing phosphorus-carbon bonds. 48 Some of the products of P-H bond activation reactions include alkenylphosphine oxides, alkenylphosphines, alkenylphosphonates, and a-amino phosphonic acids, as shown in Figure 1-7. Organophosphorus compounds have found uses as ligands 49 ' 5° for transition metals and are useful reagents in organic transformations. 5m2 A number of P-H bond activation reactions are known and will be briefly defined here. Additional emphasis will be given to hydrophosphinylation, which is the focus of the research presented in the next chapter. Hydrophosphination is the addition of a phosphine P-H bond to a C-C multiple bond to  15  form an organophosphine. Hydrophosphorylation is the addition of a phosphite P-H bond to an alkene to yield alkenylphosphonates. Hydrophosphonylation is the addition of a phosphite P-H bond to an imine to form a-amino phosphonic acids. Finally, hydrophosphinylation is the addition of a phosphine oxide P-H bond to an alkyne to form alkenylphosphine oxides as shown in Scheme 1-4. 48 R^ R^or^ R,,,,^p'0  R^  0 ^or HO OH^Hp OH R2^R2 or  alkenylphosphines^alkenylphosphine oxides^alkenylphosphonic acids NR2^NR2  R  R^ P, or R P, p,/^or R OH Hd OH O R' HO^ R'O  ,p  13 Rid OR'  R = H, alkyl group, aryl group R' = alkyl group, aryl group  a-aminophosphonic acids^alkenylphosphonates  Figure 1 7 Products of P-H bond activation reactions -  R^ = H +  0^  H  _PR2^R'^+ R2^I^  A  R'  P' R2  R2  ^  0  C  Scheme 1 4 Alkyne hydrophosphinylation -  When starting from terminal alkynes, hydrophosphinylation is a means of preparing vinylphosphine oxides, which are important starting materials in organic synthesis. 5354 Vinylphosphine oxides can be selectively reduced 55 and they can be transformed into a variety of bifunctional reagents by addition of alcohols, thiols, amines and phosphines to the olefinic bond. 48 They are also used more directly in the HomerWadsworth-Emmons olefination reaction, Scheme 1-5.56  16  0 EWG 0 II R 1 0^C\ + R3  EWG  EWG  9  P R2 + R 1 0, I Noe R2 + R1 0 R0 R2 R4^R3 Scheme 1-5 Homer-Wadsworth-Emmons olefination reaction r‘  The first Pd-catalyzed regio- and stereoselective hydrophosphinylation of alkynes yielding alkenylphosphine oxides was developed by Han et al. 57 The reaction involves Ph2P(0)H and catalytic amounts of cis-[Me2Pd(PPhMe2)2] combined with a wide range of alkynes to generate a mixture of branched and linear products. In general, the E-linear product is favored. They later discovered that a minute quantity of phosphinic acid added to the reaction mixture with resulted in higher yields and a reversal of regiochemistry, favoring the branched product. 58 A number of effective Rh catalysts were determined for the hydrophosphinylation of alkynes. 59 Among them, BrRh(PPh3)3 was an effective catalyst for a wide range of alkyne substrates. For all of the alkyne substrate and Rh catalyst combinations, (E)alkenylphosphine oxides were produced exclusively.  It was later found that Ni was an effective metal for catalysis of hydrophosphinylation of a variety of alkyne and phosphine oxide substrates. 45 By changing the ligands on Ni as well as the reaction conditions, the regioselectivity of the reaction is reversed to favor either the branched or linear product in excellent yield. 1.2.4.3 Mechanistic studies on hydrophosphinylation Han et al. propose a mechanism for hydrophosphinylation of alkynes catalyzed by  either Wilkinson's catalyst or [Rh(cod)C1]2, shown in Scheme 1-6. 59 They propose that the mechanism is initiated by oxidative addition of P-H to the Rh complex, forming a RhH species. Han and coworkers combined Ph 2 P(0)H and [C1Rh(cod)]2 in CD2C12. NMR 17  spectroscopy of this solution showed 1 11 signals that appeared at -8.1 ppm (ddq, J = 8.2, 15.5, 186.4 Hz) and -12.4 ppm (doublet of quintets, J= 13.7, 21.0 Hz). In comparison, a mixture of excess Ph2P(0)H with C1Rh(PPh 3 ) 3 in CD2C12 resulted in identical I li NMR signals at -8.1 and -12.4 ppm. However, when a 1:1 mixture of Ph2P(0)H and ClRh(PPh3)3 was combined in CD2C12, the i H NMR spectrum of this solution showed only the formation of a broad singlet at -16.2 ppm. Han suggests that in the equimolar mixture of Ph2P(0)H and ClRh(PPh3)3, a Rh-H species likely forms that includes at least one PPh3 ligand. When excess Ph2P(0)H is present, as would be the case for catalytic conditions, both complexes C1Rh(PPh3)3 and [C1Rh(cod)]2 form identical Ph2P(0)Hligated rhodium hydrides. Since there is no PPh3 present in the [C1Rh(cod)]2 and Ph2P(0)H mixture, there can be no PPh 3 ligands on this Rh-H species, common to both mixtures. Furthermore, Han suggests that since both [C1Rh(cod)]2 and C1Rh(PPh3) 3 show similar catalytic activity in the hydrophosphinylation reaction, the PPh3-free Rh-H complex is the active species for both of these catalytic reactions.  9  R  Ph2P  [Rh]  9  ^R  Scheme 1-6 Mechanism of hydrophosphinylation catalyzed by either [C1Rh(cod)]2 or  C1Rh(PPh3)3, as proposed by Han 18  1.2.5 Conclusion Pyrazolylborate rhodium complexes are known to promote stoichiometric bond activations but their catalytic activity is less well known. Based on their successful application as hydrothiolation catalysts ,26,27,41 we anticipated that Tp RRhL,, complexes would be useful in P-H bond activation reactions. Details of this work are presented in Chapter 2.  1.3 Background of olefin functionalization reactions via rhodaoxetane intermediates 1.3.1 Metallaoxetanes A metallaoxetane is a 4-membered ring structure with a metal and an oxygen, shown in Figure 1-8. L,M  2  3  M = metal, L = ligand slo  4  1  Figure 1 8 General 2-metallaoxetane structure -  Metals known to form metallaoxetanes include Pd, Pt, Re, Ni, Ag, Ir and Zr. 6(1-62 Metallaoxetanes are most well known for being invoked in some controversial mechanisms 61,63-66 and often have not been isolated or even observed. Examples of metalmediated reactions for which metallaoxetanes have been invoked as intermediates include dihydroxylation of olefins catalyzed by osmium, manganese and chromium oxides, 64 ' 67-71 catalytic epoxidation of olefins, 60 ' 72 catalytic rearrangement of epoxides to ketones, 73 Nicatalyzed reductive cyclization, 61 Ag-catalyzed epoxidation of ethylene, 62 ' 74 and Rh I 75  However, the invocation of-catlyzedsmrihognlysfepxid.  metallaoxetanes as intermediates has been controversia1 65 and until recently few relevant  19  examples 76 ' 77 were isolable or otherwise available for study. Certain metallaoxetanes can be generated by oxidation of olefin-ligated metal complexes. 78-8°  1.3.2 Oxidation of olefms Periodate, permanganate, chromate and other traditional oxidizing agents have great chemical utility but cause a detrimental environmental impact and tend to be quite expensive, especially when used stoichiometrically. 81 ' 82 Furthermore, these traditional oxidizing agents often lack functional group compatibility, limiting their application. Molecular oxygen and hydrogen peroxide are less environmentally harmful oxidants but their reactions can be difficult to contro1. 83 In the presence of certain metal complexes, oxidation of olefins by 02, or H202 becomes more manageable. Metal-mediated oxidation processes that are in use on a massive scale include Wacker oxidation and hydroformylation. 84 These reactions are typified as being relatively environmentally benign since they each use molecular oxygen as the oxidizing agent and therefore produce minimal by-products.  1.3.3 Oxidation reactions with 11 2 02 as oxidant 1.3.3.1 Rhodaoxetanes  The first isolated rhodaoxetane was prepared by researchers in the Milstein group. 85 The structure of this complex is shown in Scheme 1-7, prepared by the method shown in path a. PMe3  PMe3  Me3P4„„,.. I *Br  I  h CI 0  —  a  PMe3 (Me3Si)2NK  Me3P4644.1  je•Br 4,/PMe  b  Rh(PMe3)3Br  3  0^  0  H  Scheme 1 7 Preparation of the first isolable rhodaoxetane -  20  An X-ray crystal structure of this complex showed a planar ring structure. The Rh-C and C-0 bond distances suggest that the ring has partial carbene and ketone character, similar to the intermediate in the Tebbe olefination reaction with ketones.  86  Calhorda et al. report the first direct oxidative addition of a metal complex to a simple epoxide to yield a rhodaoxetane, shown above in Scheme 1-7, path b. 87 The specific rhodaoxetane studied in this thesis work is [(TPA) RhIII(K-2.. t., '-' ,0-2oxyethyl)] + BPh4 - (TPA = tris[(2-pyridal)methyl]amine), shown in Figure 1-9, referred to herein as TPA-rhodaoxetane. TPA-rhodaoxetane was first prepared by the Gal research group from [{Rh(i-C1)(C2H4)2}2] via [(1 2 -ethene)(K4 -TPA)Rh1 + oxidized by hydrogen peroxide, shown in Scheme 1-8. 78  LR1-1.1 0--I^L = TPA  Figure 1-9 TPA-rhodaoxetane  21  //  [{Rh(1-C1)(C2H4)2}2]  N N-N  Me0H, -78 ° C  N  s  Rh 1,1N—  —N iJ  H2 0 2  -10 ° C  ft N-^ Rh - N  61'  Scheme 1-8 Preparation of [(TPA)Rh ili(K-2 -C,0-2-oxyethyl)] + , TPA-rhodaoxetane  Tris[(2-pyridal)methyl]amine (TPA), shown in Figure 1-10, was first prepared by Anderegg et al. in 1967. 88 TPA is an 'N4'-tripodal amine ligand, so-named because it contains a central donor nitrogen atom bonded to three arms, each containing a donor nitrogen atom. It most often coordinates to a metal using all four donor nitrogen atoms. Since its creation, TPA has been used to form complexes with all of the first row metals except for Ti, as well as most of the second and third row metals and lanthanides.  89  N Figure 1-10 Tris[(2-pyridal)methyl]amine (TPA) 1.3.3.2 Mechanism of rhodaoxetane formation  Budzelaar and Blok investigated the mechanism of oxidation of (olefin)Rh i and  22  complexes to metallaoxetanes by H202 in a DFT study. 9° Their result, shown in Scheme 1-9, substantiates the suggested mechanism put forth by Gal and coworkers. 79 Heterolytic 0-0 cleavage occurs first, perhaps assisted by hydrogen bonding to the nascent hydroxide ion. A concerted mechanism for this initial step was also considered and determined not to occur since after extensive searching they could not locate a transition state for such an approach. In the next steps, intermolecular attack of coordinated HO" on coordinated olefin forms a zwitterionic intermediate, which then loses a proton to yield the rhodaoxetane. A comparison was made between the calculated energies for this transformation and one in which an oxo intermediate forms and rapidly cyclizes to the rhodaoxetane. The energy associated with the oxo species was calculated to be very high, making the first path much more likely. The stereochemistry of the H202 attack was analyzed and the cis approach of H202 with respect to the amine group was found to be slightly more favorable than the trans approach. The two possible approaches of H202 are illustrated in Scheme 1-10. The authors suggest that the energy difference between these two approaches is much higher than their calculations (0.2 kcal/mol) would indicate since in fact, no trans product is observed empirically.  (TPA)Rh^+ H202  7 O (TPA)Rh/^1  H^+ „O OH (TPA)Rh -,  v  —  - OH-^(TPA)Rh  O] H 2+ „."/  III i 2+^H 1 2+  +  ,0^ O, , , H^(TPA)R1-i^(TPA)Rh",,,  Scheme 1 9 Mechanism of oxidation of RTPA)Rhkethene)] by H202 -  23  cis approach  NC R  _ + H2O  H202  Clit ---— ^\ NCI -Rh i_N + H2O / ^N 0^  trans approach H202  not observed  Scheme 1-10 Cis and trans approaches of H202 attack 1.3.3.3 Reactivity of TPA-rhodaoxetane TPA-rhodaoxetane has been shown to react with electrophiles including acids, Mel and acetone. TPA-rhodaoxetane will undergo ring-opening by electrophiles. Protonated TPA-rhodaoxetane generates acetaldehyde by 0-H elimination at elevated temperatures or when activated by acid. These reactions are summarized in Scheme 111. 79 Contrary to what was expected, 85 ' 87 at room temperature TPA-rhodaoxetane is stable to 0-hydride elimination. However, in acidic conditions or at elevated temperatures 0-H elimination occurs to yield acetaldehyde shown in Scheme 1-11, Eq. 1. 79 TPArhodaoxetane is stable to treatment of strong bases. Gal and coworkers also found that TPA-rhodaoxetane reacted readily with electrophiles such as H + , NH4C1, Mel and H +/CH3CN, leading to ring-opened products (Scheme 1-11, Eq. 2). 79 ' 91 It was discovered that TPA-rhodaoxetane slowly reacts with acetone (Scheme 1-11, Eq. 3) to form a six-  24  membered metallacyclic ketal, indicating an ability to react with less electrophilic substrates. 79 /3-H elimination  0  /  ring opening by electrophiles 2  LRI;in 0 -1  RhL1  H  90 °C or Fl +  •  /---\^+  RX (HCI, Mel, NH4CI, H +/MeCN)  LRh OR X  insertion of acetone 3  LR1 1 00  s  -  1  Scheme 1-11 Reactivity of TPA-rhodaoxetane  Acetonitrile inserts into the protonated TPA-rhodaoxetane to form the ringopened product, which readily rearranges to a metallacyclic imino-ester. The imino-ester can then rearrange upon heating to a metallacyclic amide. 91 These transformations are shown in Scheme 1-12.  25  —1 2+  2+  N" N-^ N base, rt Rhin I N-  CH3CN  III C  OH  CH3  65 °CI  ,  7+  H 3 C^H  Scheme 1-12 Acetonitrile insertion of TPA-rhodaoxetane and subsequent rearrangements  Theoretically, rhodaoxetanes should be able to reductively eliminate an epoxide but this has never been observed. 79 Reductive elimination is likely not seen because the formation of a strained epoxide from a less strained rhodaoxetane is not thermodynamically favorable.  1.3.3.4 'N3'-rhodaoxetanes In an effort to develop the reactive potential of this series of unsubstituted 2rhodaoxetanes, the analogous 'N3' complexes were prepared, as shown in Figure 1-11. 80  Me  BP11.4 -  ICI I N  R = Me, Bu, Bz  Rh 111 " N -N ) - I  Figure 1-11 Structure of 'N3'-rhodaoxetanes  26  The 'N3' ligands make more reactive, less rigid complexes. 'N3'-Rhodaoxetanes were shown to eliminate acetaldehyde at room temperature. Acetaldehyde also readily eliminates from these complexes when they are exposed to ethene or cod to form an ethene or cod complex in near quantitative yield. Gal and co-workers attempted to produce a catalytic reaction that would prepare acetaldehyde from ethylene in the presence of 'N3'-rhodaoxetanes. They achieved all of the individual steps that in theory complete the catalytic cycle, however they did not achieve catalytic turnover when the reagents were combined in one pot. The theoretical catalytic pathway is shown in Scheme 1-13. Me C III^—11- BPh 4 N  Bz,  64  N- Rh 10 N—  BPh4-  Bz,^ Rhiii - N — 41 —N" I I ---  CD2Cl2  -  H2 02  I^+ MeCN  MeCN  0 H  C  )  + BPh4-  ethene  Scheme 1 13 Theoretical catalysis of acetaldehyde from ethene via 'N3'-rhodaoxetane -  The authors suggest two possible explanations for why catalysis is not achieved for this series of reactions. First they suggest that [(Bzbpa)Rh i] + , which results from the reductive elimination step may react faster with hydrogen peroxide than with ethylene, 27  leading to the poisoning of the active catalyst. Alternatively, perhaps further oxidation occurs to form a formylmethyl-hydroxy complex, shown in Scheme 1-14. H202  N3Rt;k i  CH 3 CN  H  OH  H BO  H BO  Scheme 1-14 Formation of a formylmethyl-hydroxide rhodium complex  1.3.4 Oxidation reactions with 0 2 as oxidant Rhodium complexes have been shown to be active catalysts for the selective oxygenation of terminal alkenes to methyl ketones. 83 For example, Read and coworkers used rhodium catalysts to facilitate the conversions of hex- 1 -ene, hept- 1 -ene and oct-1 ene to methylketones with dioxygen. The catalysts studied were RhH(CO)(PPh3)3 and RhCI(PPh3 ) 3 , the latter complex providing the best yields. 92 ' 93 They were likewise able to oxidize oct- 1 -ene and triphenylphosphine to octan-2-one and triphenylphosphine oxide with RhCI(PPh3)3. These catalytic oxygenation reactions are shown below in Scheme 115. For the most part, reactions of this type incorporate only one of the two atoms of dioxygen into the substrate and the second oxygen atom is quenched by a sacrificial hydrogen donor or a phosphine 83 catalyst:  RhCI(PPh3)3 or^0  RhH(C0)(PPh 3 ) 3.  + 1/2 02^  R CH R = C61 113, C5H11, C4H9 -  catalyst:  P,  RhCI(PPh3)3,  Ph' Ph + 1/2 02 Ph^  Ph r  I  Scheme 1-15 Catalytic oxygenation reactions 1.3.4.1 The Wacker reaction  Acetaldehyde is commercially prepared by the catalytic oxidation of ethene by  28  molecular oxygen in water, known as the Wacker process. It is a relatively environmentally benign reaction catalyzed by palladium, shown summarized in Scheme 1-16. 94 This process has a low impact on the environment because it is 100% atom efficient and does not involve the use of highly toxic solvents or reagents. PdCl 2 , CuCl2 HCI, H2O, 02  Scheme 1 16 The Wacker reaction -  Wacker-type oxidation is also possible for higher molecular weight terminal alkenes. This variation is often referred to as Wacker-Tsuji oxidation (Scheme 1-17).  95  The Wacker reaction involves oxypalladation, which is the net addition of oxygen and palladium atoms across the ethene 7c-bond, followed by 0-elimination to yield acetaldehyde. In the case of higher alkenes, oxypalladation (vida infra) can occur in Markovnikov or anti-Markovnikov fashion to yield either a methyl ketone or an aldehyde product. Markovnikov addition is by far the more typical regioselectivity for this reaction. The products are often low-boiling compared to the solvent (i.e., water), so they can be easily distilled, leaving the catalysts behind in solution for further reaction. For some higher molecular weight alkene oxidations the products do not boil at a low enough temperature to be removed by distillation. Instead the catalyst can be recovered by treating the reaction mixture with HC1 and PPh3 to make the PdC12(PPh3)2 complex which is insoluble. The products can then be extracted into an organic solvent. 0 R  )  ^or  H2O, 02  0  Scheme 1 17 Wacker-Tsuji oxidation -  29  The widely accepted mechanism for the Wacker reaction is shown in Scheme 1 1 8. 96-98 In solution, free chloride ions coordinate to PdC12 to form [PdC14] 2- . In the first two steps, water and ethene exchange with two of the chloride ions, forming a  7E-  complex. The key step of this catalysis is nucleophilic attack of a second water molecule or hydroxide ion to the coordinated ethene in an anti fashion, forming a ((3hydroxyalkyl)palladium complex. 99 This step is routinely referred to as oxypalladation since addition of the water nucleophile is facilitated by the lowered electron density of the alkene when it is in the ir-complex with electrophilic palladium. The nucleophilic addition of water is definitive of all Wacker-type oxidation reactions. Finally, a rapid succession of steps involving rearrangement and 13-elimination yields the product acetaldehyde and reduced palladium. Deuterium labelling experiments have conclusively shown that all four hydrogen atoms in the product acetaldehyde are from ethene as opposed to solvent. 99 The Cu(II) co-catalyst reoxidizes Pd(0) to Pd(II). The reduced copper is reoxidized by molecular oxygen, a stoichiometric oxidant, which is both inexpensive and readily available.  30  21/2 02 - Cl + H 2 O -  CI 1  CI - Pd - OH2 CI C  Pd° 2 Cl -  ^ CI ^  CI-Pd-OH 2  H30 + H2O CI CI - Pd - OH2  ri  OH  H+ Scheme 1 18 Mechanism of the Wacker reaction -  Wacker-Tsuji oxidations are believed to follow an analogous mechanism involving the same key steps, with the exception that the nucleophilic addition of water or hydroxyl ion can sometimes occur in a syn or an anti fashion, leading to a mixture of products. 95 ' 98  1.3.4.2 Rhodadioxolane chemistry 3-Metalla-1,2-dioxolanes have been invoked as intermediates in groups 6 and 810 metal-catalyzed olefin oxygenation reactions, including epoxidation and oxidation to ketones.' °° However, these mechanistic details could not previously be readily evaluated  31  because of a lack of isolable complexes available for study. Gal and coworkers prepared 3-rhoda-1,2-dioxolanes from [(tpa)Rh(CH2CH2)]PF6 following their successful preparation of a 2-rhodaoxetane by oxidation of this same complex with H202. These 3-rhoda-1,2-dioxolanes contain an unsubstituted 3-metalla1,2-dioxolane fragment, which was unprecedented. A solid-gas reaction of the ethylene complex in air provided a 1:1 mixture of regioisomers, shown in Scheme 1-19.  101  They  were also able to selectively prepare regioisomer b, by substituting the BPh4 - counterion for PF6". They later prepared analogous 3-irida-1,2-dioxolanes. m  \ N-  ft^re  6,z Rh  air  r' N- Rh m N-  N" Rh ni ON  a Scheme 1-19 Preparation of a 3-rhoda-1,2-dioxolane  —  b  3-Rhoda-1,2-dioxolanes were shown to rearrange to rhodium formyl methyl hydroxy complexes upon exposure to light or acid, shown in Scheme 1-20.102  32  —1+  —1+  N R^ 'N ^ R Rhffl-N^hv or H +^NNI' I^ --Nr 0,0 0  a)  ^  H-0  It  --i---  b)  ....3NI-Roil-0— ^  hv or H +  —NI' I.....-^..„\/,-,  H  0  Scheme 1 20 Rearrangement of 3 -rhoda- 1 ,2-dioxolanes -  1.3.5 Oxidation of organometallics with N2 0 as oxidant The reaction of nitrous oxide with hydride, aryl and alkyl ligands in certain metal complexes results in oxygen insertion into the metal-ligand bond, shown in Scheme 121. 103-no N20 + L- M" +^L-0-M"++ N2^L = hydride, aryl, alkyl M = Mo, Ni, Zr, Hf  Scheme 1 21 Oxygen insertion into metal complexes by N20 -  Matsunaga et al. prepared an oxanickelacycle by oxygen insertion into a nickelacyclopentane ring using nitrous oxide. 1°8 This reaction is shown in Scheme 1-22. They did not observe any intermediates but they suggest the mechanism likely involves coordination of nitrous oxide to the nickel center followed by oxygen transfer and loss of dinitrogen. Previous findings in the Hillhouse group support this proposed mechanism.111' 112  33  50 ° C, 48 h 55% yield  Scheme 1 22 Oxygen insertion into an organonickel complex by N20 -  1.3.6 Conclusion TPA-rhodaoxetane can be readily prepared and isolated78 and has shown interesting reactivity79 that could be exploited for the development of new methods for olefin functionalizations. We anticipated that TPA-rhodaoxetane could be utilized as a common reactive intermediate for several potentially catalytic olefin functionalization reactions. Details of this work are presented in Chapter 3.  34  2 Hydrophosphinylation catalyzed by pyrazolylborate rhodium complexes 2.1 Introduction Pyrazolylborate rhodium complexes are known for their ability to enable stoichiometric bond activation reactions but their catalytic activity has been less studied. 18 In a recent study, we postulated that rhodium pyrazolylborates might be sufficiently electron-rich to catalyze hydrothiolation of alkynes with alkyl thiols. 41 Indeed, we found that [Tp*Rh(PPh3)2] catalyzed hydrothiolation with high regioselectivity for branched alkyl vinyl sulfides. [Tp*Rh(PPh3)2] was found to be an effective hydrothiolation catalyst for both aryl and alkyl thiols and a range of alkynes. Based on this success we chose to further explore the potential of [Tp*Rh(PPh3)2] to catalyze reactions involving H-X bond activation as a key step (X = C, heteroatom).  2.2 Research hypotheses and goals We hypothesized that [Tp*Rh(PPh3)2] could catalyze the hydrophosphinylation of alkynes; a reaction that is believed to involve P-H bond activation as a fundamental step. 59 We further hypothesized that the regioselectivity of this reaction would be similar to that which we observed for hydrothiolation catalyzed by [Tp*Rh(PPh3)2], which results in a preference for the formation of the branched regioisomer. 41 We set out to compare a series of known hydrophosphinylation catalysts with [Tp*Rh(PPh3)2] and related [Tp*RhLn] complexes for their efficacy in the hydrophosphinylation of 1-octyne with diphenylphosphine oxide. We further planned to investigate the scope of possible substrates for hydrophosphinylation with [Tp*Rh(PPh3)2]. Auxiliary experiments were performed to investigate the mechanism of hydrophosphinylation and related P-H bond  35  activation reactions catalyzed by [Tp * Rh(PPh3)2]. Sections 2.2.1 and 2.2.2 of this chapter are based on a published account of the research conducted in our group by me and my colleague, Changsheng Cao. 113 More specifically, all of the catalytic experiments in Section 2.2.1 were performed by me and the experiments discussed in Section 2.2.2 were performed by C. Cao. The experiments performed by C. Cao are not part of any other thesis and are included here in order to provide a complete account of our findings. All other research presented in the results and discussion section 2.2 as well as the experimental section 2.3 were conducted by me.  2.3 Results and Discussion 2.3.1 Catalytic hydrophosphinylation of alkynes 2.3.1.1 Catalyst comparison  A comparison was made of known catalysts with their analogous pyrazolylborate complexes for the hydrophosphinylation reaction of diphenylphosphine oxide with 1octyne. The complexes for comparison included Wilkinson's catalyst [C1Rh(PPh3) 2 ] I, [C1Rh(cod)]2 II, [(OTf)Rh(PPh3)3] V, [Tp*Rh(PPh3)2] III, and [Tp*Rh(cod)] IV. Both Wilkinson's catalyst I and [C1Rh(cod)]2 II, are known hydrophosphinylation catalysts. 59 ROTfAh(PPh3)3] V, which was prepared in situ by adding silver triflate to Wilkinson's catalyst I, was included to see what effect a more weakly coordinating counter ion would have. It was thought that the use of a more weakly coordinating anion, i.e. triflate,  114  may  provide a Wilkinson's catalyst analog with more cationic character. The catalyst loading for all reactions was 3 mol% Rh and all reactions were performed on a 1 mmol scale. The results are presented in Table 2-1. The isolated yields are reported for the linear product only, as no branched product was observed.  36  Table 2 1 Catalyst comparison -  Ph2P(0)H 1  n-C6H13^— 2  3 mol % catalyst PhCH 3  n-C6I-113  ,./, P(0)Ph2  3a  Entrya  Catalyst  Temp, time  Isolated yield (%)  1  none  110 °C, 1 h  traceb  2  CIRh(PPh3)3 I  110 °C, 1 h  80  3c  [CIRh(cod)]2 II  110 °C, 1 h  55  4d  [(OTf)Rh(PPh3)3] V  110 °C, 1 h  74  5  Tp*Rh(PPh3)2 III  110 °C, 1 h  51  6  Tp*Rh(cod) IV  110 °C, 1 h  35  7  CIRh(PPh3)3 I  rt, 18 h  84  8  Tp*Rh(PPh3)2 III  rt, 18 h  51  9  Tp*Rh(cod) IV  rt, 18 h  25  a Reactions conducted with 1.0 equiv diphenylphosphine oxide, 1.0 equiv alkyne, 3 mol % catalyst. b Trace product observed by 1 H NMR spectroscopy. C 1.5 mol % catalyst used. d 3 mol % AgOTf.  The reactions were run for durations of either 1 or 18 h, depending on the chosen temperature. The reactions could have been run just to completion or they could be evaluated at a certain point in time. The latter option was chosen since it is operationally simpler and gives a good snapshot of the efficiency of each catalyst system. With the exception of entry 1 for which negligible product formed, all of the products were then isolated by column chromatography. Attempts were made to monitor the reactions over time using various methods including thin layer chromatography (TLC), 1 H NMR spectroscopy and gas chromatography (GC) to determine when the reaction was completed. TLC was of limited use; since none of the reactions went to 100% completion, the technique would only show that some amount of product had formed and 37  some of the starting material remained. If an internal standard was added to the reaction mixture, 1 H NMR spectroscopy could be reliably used to measure the progress of the longer reactions. For the faster reactions the reaction would continue in the NMR tube and travel time from the laboratory to the spectrometer made this type of monitoring somewhat less precise. GC-MS was used to monitor a test reaction with the conditions of 110 °C in toluene. In this case, the samples were filtered through a plug of silica gel to remove the metal complex before injection onto the column. Again there were difficulties in accurately monitoring the faster reactions since the gas chromatograph required a long run time to separate this mixture and the reaction would have long been completed by the time the analysis of the first sample was available. There was also some concern that filtration through silica may have altered the ratio of materials in the mixture. The results of the GC analysis showed that nearly all of the Ph2P(0)H starting material was gone by 15 minutes, so a set reaction time of 1 hour was chosen to ensure ample time to reach completion. Similarly for test reactions done at room temperature, 18 h was determined to be more than sufficient. Wilkinson's catalyst I (entry 2) was found to be a more effective catalyst than [C1Rh(cod)] 2 II (entry 3) for this reaction, as is consistent with the results reported by Han et al. 59 The addition of silver triflate to Wilkinson's catalyst for this reaction (entry 4) lowered the yield modestly. Han et al. report results for a series of Wilkinson's catalyst analogs in which the chloride ligand is replaced by another halide. Their results show that the effectiveness of these catalysts for hydrophosphinylation follows the order of I > Br > Cl. The result reported here that the triflate ion makes for a weaker catalyst than chloride follows the trend first established by Han et al., that more weakly  38  coordinating ligands on Rh in Wilkinson's catalyst analogs made for less effective catalysts for this reaction. The effectiveness of Wilkinson's catalyst analogs for hydrophosphinylation follows the order of I > Br > Cl > OTf. Replacing chloride with Tp* in both Wilkinson's catalyst I and [C1Rh(cod)]2 II to form [Tp*Rh(PPh3)2] III (entry 5) and [Tp*Rh(cod)] IV (entry 6), respectively, resulted in viable catalysts for hydrophosphinylation. In both cases, yields were moderate but not as high as for their chloride ligand counterparts. Interestingly, with these catalysts the linear product formed exclusively. We did not know what regioselectivity to expect for this reaction but we had reason to suspect the opposite result, that in the case of [Tp*Rh(PPh3)2] III, the branched regioisomer may form preferentially as it does in hydrothiolation reactions with this catalyst 41 since similar mechanisms have been proposed for both hydrothiolation and hydrophosphinylation. There were two sets of reaction conditions used for this comparison. Entries 7, 8 and 9 were performed at room temperature for 18 h, in toluene. Entries 2, 5 and 6 were performed at 110 °C for 1 h in toluene. For the most part, both sets of conditions produced similar yields for this hydrophosphinylation reaction. The reaction with [Tp*Rh(cod)] IV catalyst was more efficient by a difference of 10% when done at 110 °C as opposed to room temperature, in toluene. 2.3.1.2 [Tp*Rh(PPh3)2] catalyzed alkyne hydrophosphinylation - substrate scope [Tp*Rh(PPh3)2] III was chosen to explore the scope of hydrophosphinylation using a rhodium pyrazolylborate catalyst since it was found to be more effective than [Tp*Rh(cod)] IV in the preceding catalyst comparison. The results of this analysis are presented in Table 2-2.  39  Table 2-2 Alkyne substrate scope for hydrophosphinylation catalyzed by [Tp*Rh(PPh3)2] Ph2P(0)H^R1 — R2  P(0)Ph2  3 mol % Tp*Rh(PPh3)2 PhCH3, 110 ° C, 3h  1  Alkyne  Entrya  Product^Isolated yield (%) b .. 13 (0)Ph2 3a n-C6His  1  n C6Fi13  —  2  2  t-Bu  =  4  t-Bu  3  Ph  5  Ph  -  =  R2  51  P(0)Ph2 8  41  --,,,P(0)Ph2 9  17b  P(0 )P h 2 10  4^CHz0  28C  CH 0 P(0)Ph2 5  -  7  61  -  a Reactions conducted with 1.0 equiv diphenylphosphine oxide, 1.0 equiv alkyne, 3 mol % catalyst. b  Complete consumption of starting materials. b Additional unidentified precipitate formed.  All of the reactions in this comparison were done in toluene at 110 °C as these conditions were found to be generally more successful in the previous study. The reaction time was extended to 3 h to ensure completion and the results of NMR spectroscopy analysis showed no remaining starting material for these reactions. The reactions were done on a 1 mmol scale with 3 mol% catalyst. The selection of alkynes included terminal aliphatic and aromatic examples, as well as an internal aliphatic alkyne. Products 3a, 8, and 9 (entries 1 — 3) have been prepared previously by the same reaction but with a different catalyst and different conditions.  59  Han et al. used  [BrRh(PPh 3 ) 3 ] as the catalyst for this reaction in toluene for 40 min at rt to provide isolated yields of 91% for 3a (entry 1) and 93% for 8 (entry 2). The same catalyst and  40  conditions but a longer reaction time of 2 h provided 89% isolated yield for 9 (entry 3). Product 10 (entry 4) was previously prepared in 98% isolated yield by a non-catalytic 2step process involving nucleophilic substitution reactions by Bartels et al. 115 Product 11 (entry 5) has no literature precedent for comparison. The use of [Tp*Rh(PPh3)2] III does not provide an improvement on existing known yields for catalytic hydrophosphinylation of the alkynes in entries 1 — 3; however, the catalytic potential of [Tp*Rh(PPh3)2] III has been demonstrated. All of the substrates exclusively provided the vinylphosphine oxide product that would be expected from syn-addition of the P-H bond across the alkyne. The terminal alkynes (entries 1 — 4) exclusively provided linear vinylphosphine oxide products. The aliphatic alkyne substrates (entries 1, 2 and 5) had better yields than the aromatic alkyne substrates (entries 3 and 4). Of the terminal aliphatic alkynes, a straight chain alkyne (entry 1) produced a better yield than the bulkier branched alkyne (entry 2). The highest yield was obtained for 3-hexyne 7 (entry 5), a straight-chain and internal alkyne. One might expect that crowding around the metal center of the active catalyst would reduce the efficiency of this reaction. The reactions with aromatic alkyne substrates produced an additional unidentified precipitate, which presumably reduced the amount of available starting material for the formation of the desired product, effectively limiting these yields. This byproduct does not appear to be formed by oligomerization or polymerization, as has been seen for similar reactions using the [Tp*Rh(cod)] complex IV. 37 Cyclotrimerization could also potentially account for this byproduct, which nevertheless remains unidentified. There may be a competitive reaction that occurs only with aromatic alkynes in the presence of  41  [Tp*Rh(PPh3)2] III. 2.3.13 Hydrophosphinylation in the absence of catalyst  In order to determine the extent of any background reaction, diphenylphosphine oxide 1 and 1-octyne 2 were combined with no catalyst present in toluene-d8 for 1 h at room temperature. The reaction mixture was monitored by 1 H NMR spectroscopy and no product was observed in the spectrum. This experiment was repeated as described above, but the mixture was heated to 110 °C for 1 h. 1 H NMR spectroscopy of the heated mixture showed a trace of hydrophosphinylation product had formed. For this reaction both the linear 3a and branched 3b isomers were observed in a 1:1 ratio. Integration of these peaks indicated a yield of less than 1% for each isomer, an amount that is lower than can be reliably measured for this technique. It was concluded that any background hydrophosphinylation reaction for these conditions was not significant and could be disregarded as a contributing source of product in all other hydrophosphinylation reactions in this study. 2.3.1.4 Background reaction of diphenylphosphine oxide with triphenylphosphine  It was thought that a ligand exchange reaction involving diphenylphosphine oxide 1 and triphenylphosphine 12 might occur to form triphenylphoshine oxide 13. Such a  reaction could facilitate the breakdown of any catalyst containing labile triphenylphosphine ligands, resulting in an inactive complex. A mixture of triphenylphosphine 12 and diphenylphosphine oxide 1 in CDC1 3 was monitored by 31 P NMR in comparison to standards of the two reagents made up to the same concentration in separate NMR tubes. The concentration of the two reagents did not change and no new peaks formed as monitored by 31 P NMR spectroscopy over several hours. The absence of  42  any change in these spectra suggests that no competing reaction between diphenylphosphine oxide 1 and triphenylphosphine 12 occurs during the relevant timescale and conditions for the reaction of interest.  2.3.2 Crystallographic studies The mechanism of catalytic hydrophosphinylation by [C1Rh(cod)]2 II is thought to proceed via a Rh-H intermediate formed by a P-H activation step. Trzeciak et al. have observed such a species by 1 H and 31 P NMR spectroscopy as a product of the reaction of diphenylphosphine oxide 1 and [C1Rh(cod)]2 11. 116 This species likely forms by oxidative addition of P-H to Rh 1 . Based on this finding it is reasonable to presume that a Rh-H species may also be an intermediate in catalytic hydrophosphinylation using phosphinebound rhodium complexes. To test this, another member of the Love research group (C. Cao) prepared X-ray quality crystals from reactions of [C1Rh(cod)] 2 II or [Tp*Rh(PPh3)2] III with excess diphenylphosphine oxide 1. 113 These reactions were intended to mimic catalytic conditions in the absence of any alkyne. One equivalent of either [C1Rh(cod)]2 II or [Tp*Rh(PPh3)2] III was combined with 10 equivalents diphenylphosphine oxide 1 in toluene for 12 h at rt. The reaction of [C1Rh(cod)]2 II with excess diphenylphosphine oxide 1 is shown in Scheme 2-1. The X-ray diffraction analysis of the crystalline product reveals a distorted trigonal bipyramidal structure, shown in Figure 2-1.  43  HO, 0 PPh2  Ph2P(0)H 1 (10 equiv.)  rt, PhCH 3 12h  Ph2P0„, Ph 2 P 0 PPh2 HO  II [11-CiRh(cod)] 2^VI Scheme 2-1 Synthesis of complex VI  Figure 2-1 Molecular structure of complex VI. Thermal ellipsoids are drawn at the 50% probability level. Most hydrogen atoms are excluded for clarity. Selected bond lengths (A) and angles (deg): Rh-P(1) = 2.2668(6), Rh-P(2) = 2.4006(6), Rh-P(3) = 2.2880(5), Rh-P(4) = 2.3902(6), Rh-C1 = 2.4177(5), P(1)-O(1) = 1.5287(14), P(2)-O(2) = 1.5855(14), P(1)-Rh-P(3) = 88.457(19), P(1)-Rh-C1 = 128.907(19), P(3)-Rh-C1 = 142.626(19), P(2)-Rh-P(4) = 175.228(17).  Complex VI is the apparent product of exchange of cod ligand for diphenylphosphine oxide 1. There are both tautomers of diphenylphosphine oxide present in the structure, Ph2P(0)-H and Ph2P-OH. Hydrogen bonding between P-0 and 0-H is evident from the distances between these groups. It is thought that this complex may be a precursor to the active catalyst.  44  ^  The reaction of [Tp*Rh(PPh3)2] III with excess diphenylphosphine oxide 1 is shown in Scheme 2-2. 113 The crystalline product was analyzed by X-ray diffraction to reveal a dirhodium complex that has square planar geometry about both rhodium atoms. The solid-state structure of complex VII is shown in Figure 2-2.  ^/ I^Ph2 N -1\1 ,, .,'P -0,, ,OH H Rh Ph2P(0)H 1 (10 equiv.)^Ph3P1 \P - 01 \O Ph2^,E +^ 0 rt, PhCH3^ ^ ^/ ,I^ "^, O, HO^zp,..-13 -^RE:h2 N i\i.^,N ._ ,,^s,pph3 12 h, 10%^ ^• --, / ..-B, Rh Rh '^ 0-^R^ P H^N ■ ■ -N ^[ ^Ph PPh3^ i ^\ I N-NH  -  '.  VII  III [Tp*Rh(PPh3)2]^  -  c)  1  1  Scheme 2-2 Synthesis of complex VII  Figure 2-2 Molecular structure of complex VII. Thermal ellipsoids are drawn at the 50% probability level. Hydrogen atoms are excluded for clarity. Selected bond lengths (A) and angles (deg): Rh(1)-P(1) = 2.2299(11), Rh(1)-P(2) = 2.3369(11), Rh(1)-P(3) = 2.3007(11), Rh(1)-N(1) = 2.111(3), Rh(2)-P(4) = 2.2215(11), Rh(2)-P(5) = 2.2073(11), Rh(2)-N(3) = 2.136(3), Rh(2)-N(5) = 2.155(3), B(1)-0(1) = 1.487(5), B(1)-0(3) = 1.451(5), B(2)-O(5) = 1.359(5), B(4)-O(5) = 1.480(5), P(1)-Rh(1)-P(2) = 96.58(4), P(1)Rh(1)-P(3) = 84.78(4), P(2)-Rh(1)-P(3) = 167.46(4), P(4)-Rh(2)-P(5) = 88.53(4), P(4)45  Rh(2)-N(3) = 93.33(9), P(4)-Rh(2)-N(5) = 173.66(9). Complex VII is probably not an intermediate in the hydrophosphinylation pathway, but is more likely a decomposition product. There is evidence of fragmentation of the Tp* ligand, since complex VII contains no Tp* yet has four atoms of boron, probably from four molecules of Tp*. It appears that diphenylphosphine oxide 1 has exchanged with the B-N and B-H bonds in Tp*. Two of the boron atoms are four coordinate and the other two are three coordinate. Examples of fragmentation of pyrazolylborate ligands on rhodium complexes are known. 36 The formation of complex VII does indicate some instability of the catalyst. However, the yield of this  decomposition product after 12 h was low (10%) and [Tp*Rh(PPh3)2] III was shown to effect catalytic hydrophosphinylation in under 3 h. 2.3.2.1 Effect of catalyst decomposition on hydrophosphinylation  We suspected that other potentially catalytic species may be forming in solution since it is known that pyrazolylborate ligands can fragment under certain conditions. 36 Indeed, we have found evidence that Tp* can break apart, as shown by the formation of complex VII. 113 We wanted to investigate whether the Tp* fragments could contribute to active hydrophosphinylation catalysts forming with rhodium in situ. To test this, dimethylpyrazole and [C1Rh(cod)]2 II were combined in THE and stirred at room temperature overnight. NaBPh4 was added to the solution and the solvent was reduced by vacuum. A fine yellow precipitate was collected by filtration. A sample of this product was added to a solution of Ph2P(0)H 1 and 1-octyne 2 in acetone-d6 and monitored by 1 H NMR spectroscopy. The spectrum shows a small amount of the hydrophosphinylation product 3a had formed. 46  Han et al. suggest that in alkyne hydrophosphinylation reactions catalyzed by either [C1Rh(PPh3)3] I or [C1Rh(cod)]2 II, the same active catalytic species forms in solution and results in similar yields and regioselectivity for these two catalysts (see Chapter 1: Section 1.2.4.3 and below: Section 2.3.4). 59 Perhaps the reason that we observe the same regioselectivity as was obtained for other rhodium catalysts is that the pyrazolylborate ligand is being removed from Rh and the same active species is generated. To further examine the reactivity of potential catalytic species that may be forming in solution, a comparison was made between three metal complexes. The complexes used were [C1Rh(cod)]2 II, [Tp*Rh(cod)2] III prepared in situ from a mixture of [C1Rh(cod)]2 II and KTp*, and ROTDRh(pz*)3] prepared in situ from a mixture of [C1Rh(cod)] 2 II, dimethylpyrazole, and silver triflate. Stoichiometric reactions of 1octyne 1 with diphenylphosphine oxide 2 and one of three metal complexes were monitored by 1 H and 31 P NMR spectroscopy. The expected hydrophosphinylation product was observed in each of the 1 H NMR spectra, along with a corresponding disappearance of the starting materials. Based on the promising results of these initial test reactions, this set of experiments was repeated using catalytic conditions. For these catalytic reactions, the NMR data shows the disappearance of all starting diphenylphosphine oxide 1 and the appearance of (E)-1-(diphenylphosphiny1)-1-octene 3a in 100% yield. This yield was achieved in less than 25 minutes for all three reactions.  This result reveals that all three of these catalyst preparations seem to be equally active for hydrophosphinylation performed on a small scale.  2.3.3 Other P H activation reactions -  P-H sources other than diphenylphosphine oxide 1 were considered for reaction  47  with alkynes catalyzed by rhodium pyrazolylborate complexes. The other P-H bond sources that were considered included Ph2PH 14, (MeO)2 P(0)H 15, and (EtO)2P(0)H 16. 2.3.3.1 Reactions of [TpRh(cod)] with diphenylphosphine  A small-scale catalytic reaction was performed with diphenylphosphine 14 in combination with equimolar 1-octyne 2 and 3 mol % of [TpRh(cod)] VIII in toluene-d8 in an NMR tube. A small amount of rhodium hydride formed immediately at room temperature, as observed by 1 H NMR spectroscopy (5 -13.8). After several days at room temperature, the reaction showed the formation of a trace amount of hydrophosphination product 3a. The reaction mixture was heated for 2 h to 80 ° C and monitored by 1 H NMR spectroscopy but no further product formed from this treatment. [TpRh(cod)] VIII was shown as a non-viable catalyst with low activity for the hydrophosphination of 1-octyne 2 with diphenylphosphine 14 for these reaction conditions. The formation of a hydride in the above reaction suggests that [TpRh(cod)] VIII activated the diphenylphosphine P-H bond and this result inspired further study into the stoichiometric reaction of [TpRh(cod)] VIII with diphenylphosphine 14, monitored by 1H  and 31 P NMR spectroscopy. The appearance of Rh-H peaks in the 1 H NMR spectrum  suggests that P-H activation of diphenylphosphine 14 had occurred. 2.3.3.2 Reactions of [TpRh(cod)] with dialkylphosphites  Small-scale catalytic reactions were performed with dialkylphosphites ((MeO)2P(0)H 15 and (EtO)2P(0)H 16) in combination with equimolar 1-octyne 2 and 3 mol % of [TpRh(cod)] VIII in toluene-d8 in an NMR tube. The immediate formation of small amounts of rhodium hydrides (around -14 ppm) were observed by 1 H NMR spectroscopy at room temperature. Heating the reaction mixtures to 80 ° C for 2 h had  48  produced no further product as observed by 1 H NMR spectroscopy. [TpRh(cod)] VIII was not shown to be an active catalyst for the hydrophosphorylation of 1-alkyne 2 with dialkylphosphites for these reaction conditions. Again, the formation of hydrides suggests that [TpRh(cod)] VIII activated P-H bonds so stoichiometric reactions of [TpRh(cod)] VIII with dialkylphosphites were performed and monitored by 1 H and 31 P NMR spectroscopy. The stoichiometric reactions of [TpRh(cod)] VIII with dialkylphosphites ((MeO)2P(0)H 15 and (Et0)2P(0)H 16) showed peaks in their 1 H NMR spectra indicative of the formation of Rh-H, suggesting P-H bond activation. These spectra have two very interesting features worth noting. First, they each have broad singlet peaks around 17 ppm, the exact location seems to vary depending on concentration and temperature. Second, they each have hydride peaks at around —14 ppm with very well-resolved splitting into a doublet of double doublets (ddd). For the product formed from (MeO)2P(0)H 15, 8 -14.3 (ddd, = 20.8 Hz, 24-11 24.4 Hz, 2Jp_if = 13.6 Hz, Rh-H). For the product formed from (EtO)2P(0)H 16, 8 -14.2 (ddd, 1 JR1141 = 20.9 Hz, 2Jp_ii = 24.3 Hz, 2Jp4i = 13.3 Hz, Rh-H). The broad singlets at 17 ppm are of interest because there are very few types of protons known to give peaks at such low field. Peaks found in this region are indicative of very strong hydrogen bonding resulting in an unusually highly deshielded proton. Molecules that are known to have proton peaks appear as high as 16 ppm include intermolecular hydrogen bonded alcohols and pyrroles. 117 The well-resolved ddd hydrides indicate three strong couplings to the rhodium hydride proton. One of these splittings is due to direct coupling with 103 Rh. The broad band 31 P { 1 H} NMR spectrum shows the hydride peak has simplified to a doublet. The  49  other two splittings are almost certainly two-bond couplings with  31 P.  As there are two  unique coupling constants, this indicates that there must be two different  31 P  environments. Other features of the 1 H NMR spectra suggest that there are four distinct alkyl group environments of equivalent abundance. A 2D COSY spectrum was collected of the diethyl phosphite 16 and [TpRh(cod)] VIII reaction mixture but did not reveal any new information since the species of interest forms in concentrations too low to be usable for this experiment. Attempts to isolate the complex and prepare more concentrated samples were unsuccessful. The 31 P { 1 1-I} NMR spectrum shows two doublet of doublets (dd) of equivalent abundance at 6 113.9 (J = 36.5, J = 190.1) and 6 84.9 (J = 35.9, J = 163.9). When the 1 I-1 decoupler is turned off for the 31 P NMR spectrum, these signals appear as poorly resolved doublets of double doublets. In a similar experiment, Trzeciak and ZiOlkowski react [Rh(acac)(CO)2] with excess diphenylphosphite to form the Rh" complex, [HRh{[P(OPh)20]2H12], shown in its two isomeric forms in Scheme 2-3. 116 These proposed structures were based on 1 H and 31  P NMR studies. 1 H NMR spectroscopy showed a doublet of quintets for the square  pyramidal isomer and doublet of double quartets for the trigonal bipyramidal isomer. They suggest that the large Ap_H) (229 Hz) indicates that the hydride and a phosphorus are located trans to each other in the trigonal bipyramidal structure. The cyclic [P(OPh)2O]2H ligand forms from the coordination of two molecules of diphenylphosphite, one of each tautomeric form represented. The isomerism of hydrogen phosphonates is shown in Scheme 2-4. 118 The tetracoordinated phosphorus tautomer (A) coordinates to Rh by oxidative addition, thereby providing the hydride ligand as well. The tricoordinated  50  phosphorus tautomer (B) coordinates datively from the lone pair on phosphorus. Hydrogen bonding stabilizes the resulting cyclic [P(OPh)20]2H ligand. R2^R2  I-1^R2  R2 1  ' ,‘P 0 H.:"^"Rh'^-F1 -  ^p0,_  0^I^P 0 -  R2^R2  H-0  H  R = OPh  -  --PR2 R2  Scheme 2 3 Isomerism of [HRh{[P(OPh)20]2H}2] -  9 RO-F;OH RO^RO  R = alkyl, Ph  A  Scheme 2 4 Tautomerism of hydrogen phosphonates -  Figure 2-3 shows the general proposed structure that fits the NMR spectroscopic evidence found for the reactions of [TpRh(cod)] VIII with alkylphosphites ((Me0)2P(0)H 15 and (Et0)2P(0)H) 16. This proposed structure was inspired in part by the similarity of the Trzeciak and ZiOlkowski experiment with the reactions presented here between [TpRh(cod)] VIII and dialkylphosphites. They observe a doublet of double quartets for their trigonal bipyramidal complex and one would expect a doublet of double doublets for the analogous structure with two fewer equatorial phosphorus nuclei, as in the proposed complexes IX and X. The approximately 17 ppm broad singlet peaks might be the signals for the O-H on (R0)2P(OH), hydrogen bonded to (R0)2P(0) . A cyclic -  [P(OR)20]2H ligand is consistent with the Trzeciak and ZiOlkowski example as well as with our result for complex VI. The structure shown in Figure 2-4 is based on the X-ray crystal structure that we obtained for complex VI.  51  RO RO,\  Ts / 0 Rh—P H^ 141 I \O R " OR  IX:R = Me X: R = Et  Figure 2 3 Structures of proposed complexes IX and X -  HO, O PPh2 Ph 2 1S,„„ Ph2p' O P h2 P HO Figure 2-4  Structure of complex VI  Trzeciak and ZiOlkowski reported only the hydride peaks for their 1 1-1 NMR results; no low-field signals were reported for their complex, [HRh{[P(OPh)20]2H} 2 ]. One might expect that such a structure could exhibit low-field peaks in the 1 H NMR spectrum since its P-O-H-O-P moiety has much in common with that of intermolecular hydrogen bonded alcohols, known for their low-field peaks. Several attempts were made to prepare high quality crystals of the products of reactions of [TpRh(cod)] VIII with dialkyiphosphites in an effort to reveal the structures of these products by X-ray crystallography. For these reactions, a toluene solution of the reaction mixture was filtered through Celite then concentrated under vacuum. The concentrates were layered with hexanes and left to precipitate. Within minutes, a fine yellow precipitate crashed out of solution. Another technique to prepare crystals involved placing concentrated toluene solutions in small vials, inside of larger vials and adding pentane to the outer vials. The outer vials were capped and placed in a freezer inside the glovebox for several days. By this technique, no precipitates formed. These samples have been left in the glovebox over many months in the hope that crystals may form one day. 52  2.3.4 Mechanism of P-H bond activation reactions Trzeciak and ZiOlkowski observed two rhodium hydride species in the 1 H NMR spectrum of their reaction of [Rh(acac)(CO)2] with excess diphenylphosphite, discussed above and shown in Scheme 2-3. 116 Similarly in their mechanistic investigations on hydrophosphinylation, Han et al. observed two Rh-H species, one with a doublet of double quartets and one with a doublet of quintets in the 1 H NMR spectrum (see Chapter 1, Section 1.2.4.3). 59 The doublet of quintets suggests that the hydride is coupled to rhodium and to four identical phosphorus nuclei. The doublet of double quartets suggests that in addition to the rhodium coupling, there are four phosphorus nuclei but one of these is in a unique environment from the other three. In the reaction between [TpRh(cod)] VIII and excess dialkylphosphites performed by our group, a Rh-H species is observed as a doublet of double doublets in the 1 H NMR spectrum. This suggests that there are just two phosphorus nuclei on rhodium, each in unique environments. Presumably only two phosphorus ligands add to rhodium in this example because Tp remains attached as well. The results of three research groups (Trzeciak and ZiOlkowski, Han et al., and our group) seem to consistently show that when certain Rh complexes are combined with an excess of secondary phosphine oxides or dialkylphosphites (both P-H sources) that P-H activation occurs to yield rhodium hydrides ligated by phosphine oxides or dialkylphosphites. Since oxidative addition of P-H to the rhodium complex occurs immediately for each of these examples, it is likely that this is a common initial step in the mechanism of P-H activation reactions catalyzed by pyrazolylborate rhodium complexes or by [C1Rh(cod)] 2 II or C1Rh(PPh3)3 I and that the overall mechanisms for these reactions are likely very similar to that proposed by Han et al. for rhodiumcatalyzed hydrophosphinylation of alkynes discussed in Chapter 1. 59 A proposed general 53  mechanism for P-H bond activations catalyzed by rhodium complexes is shown in Scheme 2-5. In this generalized mechanism, oxidative addition of a P-H bond to the Rh complex forms a Rh-H species in the first step. The next step is a migratory insertion of the alkyne into the Rh-H bond: Finally, reductive elimination yields the product and regeneration of the catalyst. *1:  R^  *lop  R^  [Rh]^*P—H  R^*P—[RN—H  = ^R *P—H = a secondary phosphine oxide or dialkylphosphite  Scheme 2-5 Generalized mechanism of P-H activation reactions catalyzed by rhodium complexes  2.4 Conclusions [Tp*Rh(cod)] IV and [Tp*Rh(PPh3)2] III have now been shown to catalyze hydrophosphinylation of 1-octyne 2 with diphenylphosphine oxide 1, adding to our knowledge of rhodium pyrazolylborate reactivity. The yields for catalytic hydrophosphinylation by these two rhodium pyrazolylborates were moderate and not as high as the yields for these reactions with Wilkinson's catalyst I. [Tp*Rh(PPh3) 2 ] III was further shown to catalyze hydrophosphinylation of a range of alkyne substrates, all of which provided exclusively the vinylphosphine oxide resulting from syn-addition of P-H across the alkyne bond. This regioselectivity contrasts with results for hydrothiolation reactions, where these Tp*RhL n complexes mainly provided the branched products. 41  54  Aliphatic alkynes provided higher yields than aromatic alkynes. An internal aliphatic alkyne provided the highest yield in the group. It appears that product formation may be directed by the steric bulk of the ligands on rhodium. We propose that hydrophosphinylation catalyzed by rhodium pyrazolylborate complexes follows an analogous mechanism to that proposed by Han et al. for hydrophosphinylation by [C1Rh(PPh3)3] I or [C1Rh(cod)]2 II. There is evidence that related P-H bond activation reactions probably also follow a similar mechanism.  2.5 Experimental Procedures 2.5.1 General Methods Manipulation of metallic compounds was performed using standard Schlenk techniques under an atmosphere of dry nitrogen or in a nitrogen-filled Vacuum Atmospheres or MBraun glovebox ([02] < 2 ppm). NMR spectra were recorded on Bruker Avance 300 or Bruker Avance 400 spectrometers. Toluene and THE were dried by passage through solvent purification columns. 119 CDC1 3 was vacuum-transferred from P2O5 and degassed prior to use. Acetone-d6 and 1,2-dichloroethane were distilled and degassed prior to use. Toluene-d8 was degassed prior to use. All other reagents and solvents were obtained from commercial sources and used as received. 1 H and 31 P { 1 1-1} NMR spectra are reported in parts per million and were referenced to residual solvent. Coupling constant values were extracted assuming first-order coupling.  31 P  NMR  spectra were referenced to an external 85% H3PO4 standard. All spectra were obtained at 25 ° C, unless otherwise stated. GC chromatographs were recorded on a Varian CP-3800 or an HP 5890 Series II gas chromatograph. Mass spectra were recorded on a Kratos MS50 mass spectrometer.  55  2.5.1.1 Preparation of Tp*Rh(PPh3)2 III N ,,PPh3 N N,^ Rh^KCI H^ ' PPh3 I  Ph3P, .PPh 3  +^Rh  ■ Ph 3 P ^ CI ''  KG  A suspension of [C1Rh(PPh3)3] I (1.00 g, 1.08 mmol) and KTp* 17 (potassium hydrotris {3,5-dimethylpyrazolyl} borate) (0.364 g, 1.08 mmol) in THF (15 mL) was placed in a 50 mL Schlenk flask equipped with a magnetic stir bar and was stirred at room temperature inside a glovebox for 2 h. The suspension dissolved fully and turned from dark red to orange within 1 h. After 2 h, most of the THF was removed by vacuum. Toluene was added and the resultant slurry was filtered through Celite to remove KC1. The solvent was removed by vacuum via Schlenk line from the crude product. To improve the purity, the product was redissolved in a minimal quantity of toluene and then hexane was added to the toluene solution and the product precipitated. The precipitate was collected and washed 5 times with 1 — 2 mL hexane to ensure that no residual starting material remained, as confirmed by the 31 P NMR spectrum. Yield of crude product: 0.92 g (92%). The product identity was confirmed by comparing the 31 P NMR spectrum with reported data. 28 2.5.1.2 Preparation of [Tp*Rh(cod)] IV —N ^ / I N i\j , 1' 3 N -N + H (:)i\J_ N \ KG^  ,CI 1/2  17^  Rh^Rfi  + KCI  CI II  ^  IV  A suspension of [C1Rh(cod)]2 II (0.083 g, 0.166 mmol) and KTp* 17 (0.11 g,  56  0.333 mmol) in 15 mL THF was placed in a small Schlenk flask equipped with a magnetic stir bar and stirred at room temperature inside a glovebox overnight. Most of the THF was removed by vacuum. Toluene was added and the resultant slurry was filtered through Celite to remove KC1. The solvent was removed by vacuum. Yield: 0.11 g (65%). The product identity was confirmed by comparing the 1 H NMR spectrum with reported data. 22 2.5.1.3 Preparation of (E)-1-(diphenylphosphinyl)-1-octene 3 0  3 mol% [Tp*Rh(PPh3)2]  Ph I H + n-C6H 13 ^ ^ n-C6F113P(°)Ph2 Ph 2^ 3  Tp*Rh(PPh3)2 III (28 mg, 0.030 mmol, 3 mol%), toluene (1 mL), diphenylphosphine oxide 1 (207 mg, 1.0 mmol) and 1-octyne 2 (147 1 0 mmol) were combined in the glove box in a 15 mL Schlenk flask equipped with a magnetic stir bar and a glass stopper. The flask was removed from the glove box and heated in an oil bath at 110 °C for 3 h. After the reaction was completed, the resulting mixture was concentrated under Schlenk line vacuum. Flash chromatography (Si02 and a 1:1 mixture of hexanes and ethyl acetate as eluent) provided the product as a white solid. Yield: 0.161 g (51%). The product identity was confirmed by comparing the 1 H and 31 P NMR spectra with reported data. 59 2.5.1.4 General small-scale catalytic hydrophosphinylation procedure  Trimethylsilane (TMS) (0.1 mmol, internal standard), [C1Rh(cod)]2 (0.015 mmol, 3 mol% Rh), toluene-d8 (500 pL), diphenylphosphine oxide 1 (21 mg, 0.1 mmol) and 1octyne 2 (15 pL, 0.1 mmol) were combined in the glove box in an NMR tube. The NMR tube was sealed and shaken to mix the contents. The reactions were maintained at room 57  temperature. 1 1-1 and 31 P NMR spectra were obtained as soon as possible after combining reagents (15 to 25 minutes) and repeated after approximately 1 h, and 3 days. 2.5.1.5 Preparation of (E)-1-(diphenylphosphinyl)-3,3-dimethyl-1-butene 8 0 3 mol% [Tp*Rh(PPh3)2] I I^ Ph- I H +^t-Bu Ph  III ^P(0)Ph2 ^t-Bu  1^4^  8  Tp*Rh(PPh3)2 III (28 mg, 0.030 mmol, 3 mol%), toluene (1 mL), diphenylphosphine oxide 1 (207 mg, 1.0 mmol) and 3,3-dimethyl-l-butyne 4 (12 lit, 1.0 mmol) were combined in the glove box in a 15 mL Schlenk flask equipped with a magnetic stir bar and a glass stopper. The flask was removed from the glove box and heated in an oil bath at 110 °C for 3 hours. After the reaction was completed, the resulting mixture was concentrated under Schlenk line vacuum. Flash chromatography (SiO2 and a 1:1 mixture of hexanes and ethyl acetate as eluent) provided the product as a white solid. Yield: 0.118 g (41%). The product identity was confirmed by comparing the 1 1-1 and 31 P NMR spectra with reported data. 59 2.5.1.6 Preparation of (E)-1-(diphenylphosphinyl)-2-phenylethene 9 0 3 mol% [Tp*Rh(PPh3)2] I I^ Ph- I H +^Ph Ph  III ^  5^  ^P(0)Ph2  Ph  9  Tp*Rh(PPh3)2 III (28 mg, 0.030 mmol, 3 mol%), toluene (1 mL), diphenylphosphine oxide 1 (207 mg, 1.0 mmol) and phenylacetylene 5 (11 'IL, 1 0 mmol) were combined in the glove box in a 15 mL Schlenk flask equipped with a magnetic stir bar and a glass stopper. The flask was removed from the glove box and heated in an oil  58  bath at 110 °C for 3 hours. After the reaction was completed, the resulting mixture was concentrated under Schlenk line vacuum. Flash chromatography (Si02 and a 1:1 mixture of hexanes and ethyl acetate as eluent) provided the product as a white solid. Yield: 0.0529 g (17%). The product identity was confirmed by comparing the 1 H and 31 P NMR spectra with reported data. 59 2.5.1.7 Preparation of (E)-1-(diphenylphosphinyl)-2-(4-methoxyphenyl)ethane 10 0 3 mol% [Tp*Rh(PPh3)2]^ P(0)Ph2 I I^ Ph  -  P^ III I H + H3CO Ph^ 1^6  CH3O 10  Tp*Rh(PPh3)2 III (28 mg, 0.030 mmol, 3 mol%), toluene (1 mL), diphenylphosphine oxide 1 (207 mg, 1 0 mmol) and 1-ethynyl-4-methoxybenzene 6 (13 pL, 1.0 mmol) were combined in the glove box in a 15 mL Schlenk flask equipped with a magnetic stir bar and a glass stopper. The flask was removed from the glove box and heated in an oil bath at 110 °C for 3 hours. After the reaction was completed, the resulting mixture was concentrated under Schlenk line vacuum. Flash chromatography (Si02 and a 1:1 mixture of hexanes and ethyl acetate as eluent) provided the product as a white solid. Yield: 0.0927 g (28%). 31 P NMR (CDC13, 121 MHz) 8 30.44. The product identity was confirmed by comparing the 1 H NMR spectrum with reported data. 115 2.5.1.8 Preparation of (E)-3-(diphenylphosphinyl)-3-hexene 11 0 I I^ 3 mol% [Tp*Rh(PPh3)2] ^p(0)Ph2 Ph I H Ph -  1^7^  11  Tp*Rh(PPh 3 )2 III (28 mg, 0.030 mmol, 3 mol%), toluene (1 mL), diphenylphosphine oxide 1 (207 mg, 1.0 mmol) and 3-hexyne 7 (11 !IL, 1.0 mmol) were 59  ^  combined in the glove box in a 15 mL Schlenk flask equipped with a magnetic stir bar and a glass stopper. The flask was removed from the glove box and heated in an oil bath and at 110 °C for 3 hours. After the reaction was completed, the resulting mixture was concentrated under Schlenk line vacuum. Flash chromatography (SiO2 and a 1:1 mixture of hexanes and ethyl acetate as eluent) provided the product as a white solid. Yield: 0.172 g (61%). 1 H NMR (C6D6, 300 MHz) 8 7.91 - 7.83 (m, 4 H, Ph), 7.24 — 7.16 (m, 6 H, Ph), 6.22 (dt, Jp_H = 21.0 Hz, J= 7.20 Hz, 1 H, C-II), 2.38 - 2.30 (m, 2 H), 1.99 - 1.94 (m, 2 H), 0.99 (t, 3 H), 0.79 (t, 3 H). 13 C NMR (C6D6, 75 MHz) 8 147.51 (d, 1 C), 136.35 (d, 2 C, Ph), 132.69 (d, 4 C, Ph), 131.84 (d, 2 C, Ph), 128.88 (d, 4 C, Ph), 22.51 (br s, 1 C), 21.83 (br s, 1 C), 15.20 (br s, 1 C), 13.86 (br s, 1 C). 31 P NMR (C6D 6 , 121 MHz) S 29.17. HRMS (EI) m/z calcd for C18H210P: 284.1330; found: 284.1335. 2.5.1.9 Background reaction procedure 0 Ph  r:1 )  no catalyst  n-C 6 H 13 Ph 1^2^ H + n C 6 H 13 -  P(C))Ph2 + n-C6Fl13P(0)Ph2  3a^ 3b <1%^ < 1%  Toluene (1 mL), diphenylphosphine oxide 1 (207 mg, 1 0 mmol) and 1-octyne 2 (147 'IL, 1.0 mmol) were combined in the glove box in a 15 mL Schlenk flask equipped with a magnetic stir bar and a glass stopper. The flask was removed from the glove box and heated in an oil bath at 110 °C for 3 h. The resulting mixture was concentrated under Schlenk line vacuum. A sample of the crude reaction mixture was dissolved in C6D6 in an NMR tube. The 1 H NMR spectrum showed a trace (< 1%) amount of each isomer of hydrophosphinylation product had formed. The product identity was confirmed by comparing the 1 H and 31 P NMR spectra with reported data. 59  60  2.5.1.10 Background reaction of diphenylphosphine oxide with triphenylphosphine  Ph2P(0)H + Ph 3 P^no reaction 1^12  A 1:1 mixture of triphenylphosphine 12 and diphenylphosphine oxide 1 in CDC13  was monitored by 31 P NMR in comparison to standards of the two reagents made up to the same concentration in separate NMR tubes. The concentration of the two reagents did not change and no new peaks formed as monitored by 31 P NMR spectroscopy over 2 hours. After 3 days at room temperature the 31 P NMR spectrum still showed no evidence of any reaction. 2.5.1.11 Preparation of [TpRh(cod)] VIII —N 0  N N^1‘1-1\1  H ,S, N,N + 1/2 -  K®^  \ I  5  Rh ^Rh --..^ / ■ I " / CI  cN N H  / 'Rh  + PPh3 + KCI  18  A suspension of [C1Rh(cod)] 2 II (0.083 g, 0.166 mmol) and KTp 18 (potassium hydrotris{pyrazolyl}borate) (0.084 g, 0.333 mmol) in 15 mL THF was placed in a small Schlenk flask equipped with a magnetic stir bar and stirred at room temperature inside a glovebox overnight. Most of the THF was removed by vacuum. Toluene was added and the resultant slurry was filtered through Celite to remove KC1. The solvent was removed by vacuum. Yield: 0.10 g (70%). The product identity was confirmed by comparing the 1 1-1NMR  spectrum with reported data. 22  61  2.5.1.12 Preparation of complex IX MeO  —N N  P  0  ,B, H N^\ 'N  + 2 equiv.  Me0 I OH  VIII^  OMe  15  H ,B  LO  H  NOMe \ I^OMe IX^+ cod  TpRh(cod) VIII (9 mg, 0.02 mmol), toluene-d8 (600 A), dimethylphosphite 15 (9 tit, 0.1 mmol) were combined in the glove box in an NMR tube. A trace amount of complex IX was observed by NMR spectroscopy in the reaction mixture. 1 H NMR (toluene-d8, 400 MHz) 6 17.2 (br s), -14.3 (ddd, 1../Rh_H = 20.8 Hz, 2Jp_H = 24.4 Hz, 2./P-H = 13.6 Hz, Rh-H). 31 P NMR (toluene-d8, 162 MHz) 6 116.4 (dd, J = 207 Hz, J = 37.3 Hz), 86.99 (dd, J= 37.9 Hz, J= 165 Hz). 2.5.1.13 Preparation of complex X —N N ^1 B,^Rh H^■ N N \  Et0 0^ Et0\\ _ 0 H I I^ p^I "-P N,^1‘1"-Nii,,„ ^/ 0  + 2 equiv. Et0 I OH^ ti B., ^...„.:Rih-17 OEt^....„ N^H NOEt \ I^OEt + cod 18 X VIII  TpRh(cod) VIII (9 mg, 0.02 mmol), toluene-d8 (600 tt,L), diethylphosphite 18 (13 A, 0.1 mmol) were combined in the glove box in an NMR tube. A trace amount of complex X was observed in the reaction mixture by NMR spectroscopy. 1 H NMR (toluene-d8, 400 MHz) 6 17.3 (br s), 4.5 — 3.5 (4 m, 4 x 2 H, OCH2CH 3 ), 1.35, 1.12, 1.05, 0.89 (4 t, 4 x 3 H, Me), -14.2 (ddd, 1 JRh_H = 20.9 Hz, 2Jp-H = 24.3 Hz, 2Jp_ii = 13.3 Hz, Rh-  H). 31 P NMR (toluene-d8, 162 MHz) 6 113.0 (dd, J = 190 Hz, J = 36.2 Hz), 84.2 (dd, J = 164 Hz, J= 36.6 Hz).  62  3 Direct functionalization of olefins via 2rhodaoxetanes 3.1 Introduction The field of metal-mediated olefin functionalizations encompasses a vast range of possible reactions that follow various different mechanisms. This project focuses on reactions that are all expected to proceed along analogous mechanisms via a common intermediate, a 2-metallaoxetane. 2-Metallaoxetanes can theoretically undergo  0-H  elimination, ring-opening and reductive elimination reactions, shown in Scheme 3-1. Any of these reactions might potentially be incorporated into a catalytic cycle, enabling a wide range of possible products. We postulated that metallaoxetanes could be utilized as reactive intermediates for catalytic functionalizations of olefins. The reactions chosen for study in this project included oxidation, aminohydroxylation and arylhydroxylation of olefins via metallaoxetanes. Scheme 3-2 shows examples of these reactions via a 2metallaoxetane intermediate of the simplest olefin, ethylene.  fl-H elimination  ^ L,M H  ring-opening  HX  reductive elimination  /  L,M^OH X  LAM +  Scheme 3 1 Reactivity of 2-metallaoxetanes -  63  ^  oxidation 1^0  - L A M^)L- H  LAM-1 ^aminohydroxylation 2 ^Lnm ---,OH HN--,,.,-OH 0 -1^NH2R^I^- L A M^R NH R  N  arylhydroxylation 3  LA M  RB(OH)2  H2O  _  - LAM  R  Scheme 3-2 Oxidation, aminohydroxylation and arylhydroxylation of ethylene, via a 2-  metallaoxetane intermediate  The metallaoxetane chosen for the basis of this study was a 2-rhodaoxetane, [(TPA)Rhm (c2 _C,0-2-oxyethyl)] + BP114 - XIII, developed by Gal and coworkers, shown in Figure 3-1. 78 This specific 2-rhodaoxetane complex can be readily generated and isolated, and has shown interesting reactivity79 that could be exploited for use in potentially catalytic reactions, including oxidation, aminohydroxylation and arylhydroxylation of olefins. —1+ BPh4  I  N Rh 1 " —N - I  Figure 3 1 [(TPA) RhIII '1(2_ C,0 2 oxyethyDr BPh4 XIII -  -  -  -  3.2 Research goals 3.2.1 Catalysis involving a 2-rhodaoxetane intermediate Reactions of 2-rhodaoxetanes could potentially be incorporated into catalytic 64  cycles that would lead to a range of products from a common intermediate, as shown in Scheme 3-3. The use of rhodaoxetanes in these reactions would present a mechanistically novel approach to olefin functionalization. Initially we planned to focus on the stoichiometric reactivity of rhodaoxetanes, with the ultimate goal of developing these reactions as catalytic processes. It was important that these reactions eventually be catalytic because of the expense associated with any rhodium compounds. These reactions could make economical sense only if tiny quantities of rhodium are used. Importantly, catalytic turnover would also lessen the environmental impact of these reactions. C2H2  C2H2  ,,.....„...---^------„,,^ .---^----,,k L,Rh^LnRh—li^ L,Rh^LnRh-11 R2N  -Th^y [0,^  1 H3C H  (I  L,Rh I  OH /—OH  LnRhi  H  R2N HNR2  oxidation of ethylene  ^  aminohydroxylation of ethylene  C2H2  L Rh^LnRh—M H2O Ar - B(OH) 3 OH^OB(OH)2  [0]  L n Rh  OB OH)2 L Rh  Ar  0  (  I  ArB(OH) 2 arylhydroxylation of ethylene  Scheme 3 3 Proposed catalytic cycles involving a 2-rhodaoxetane intermediate -  65  We planned to first develop catalytic reactions with ethylene and later expand the scope of olefin substrates. If metallaoxetanes could be readily generated from olefins, these catalytic cycles would be very useful. Gal and coworkers attempted to develop a variation of the catalytic oxidation of ethylene involving a reactive 'N3'-rhodaoxetane shown in Scheme 1.13 of the introductory chapter. 8° As previously discussed, catalytic turnover was unsuccessful for this reaction sequence in one pot although the individual steps were achieved separately. They suggest that H202 may be interfering in one or more ways that compete with the desired reactions. One possibility is that coordination by H202 is faster than ethylene and this leads to poisoning of the active catalyst. Additionally, H202 may be further oxidizing the 2-rhodaoxetane intermediate to a formylmethyl-hydroxy complex. Perhaps an alternative oxidant could be found that would be more successful, for instance, nitrous oxide. TPA-rhodaoxetane and other related metallaoxetanes are isolable, which means that certain reaction steps of the potentially catalytic cycles can be studied individually. This feature provides the investigators with more control over the many aspects of this research. Hopefully it should be possible to fine-tune the catalyst and conditions in order to achieve catalytic turnover for these reactions.  3.2.2 Regioselectivity of olefin functionalization reactions via 2rhodaoxetanes Once the proposed olefin functionalization reactions have been achieved with ethylene, the next step of this project would be to develop the regioselectivity of these transformations by exploring a range of possible unsymmetrical olefin substrates.  66  Working with the simplest olefin, ethylene, there are no regiochemistry issues with which to contend. Scheme 3-4 shows how the use of unsymmetrical olefins could lead to two possible regioisomers of 2-rhodaoxetanes. R 1^R1^ R1 L„ Rh 1 LnRh--11^H202 L n Rh7 or L n Rh---/ 0-0 — R1  Scheme 3-4 Possible regioisomers of 2-rhodaoxetanes formed from a mono-substituted olefin  This regioselectivity would be explored for a number of unsymmetrical olefins and for different ligands on the rhodium center. Scheme 3-5 shows the possible outcomes of using monosubstituted olefins in each of the three types of reactions we planned to pursue for this project. 0  oxidation 'I  - RhL  R1  or R 1  A ,R1 LRh--'  LRh-  or R1  aminohydroxylation 2  H2NR2 , - RhL  ^  R1  OH^NHR2 NHR2 or Ri JOH C  D  OH  Ar  L = TPA arylhydroxylation 3  Or  1.ArB(OH)2, - RhL 2. H 2 O  R1  OH  E  Scheme 3-5 Possible outcomes of the proposed functionalization reactions with monosubstituted olefins Regioselectivity of rhodaoxetane formation would determine whether Markovnikov or anti-Markovnikov product formation would be favored. Our approach involves setting the stereochemistry at the oxidation step, when discrete Rh-C and Rh-0  67  bonds are formed in close proximity to the other ligands on the metal center. Changes made to the auxiliary ligands will alter the sterics and electronics of the complex, which should affect the regiocontrol of these reactions. A range of ligands will be explored in an effort to improve the regioselectivity of these reactions for various olefinic substrates.  3.2.3 Oxidation via TPA rhodaoxetane -  Gal and coworkers have demonstrated that 2-rhodaoxetanes can eliminate acetaldehyde either by heating to 65 °C or by activation with the non-coordinating acid [H(OEt2)2]B(C6H3(CF3) 2 )4, HBArfA. 79 ' 8° A catalytic version of this reaction remains to be developed. We eventually plan to explore a range of substituted olefinic substrates for the potential development of regio- and enantioselective versions of this reaction. Equation 1 of Scheme 3-5 shows the two possible regioisomeric products of the oxidation of monosubstituted olefins, methyl ketones (A) or aldehydes (B). The aldehyde product (B) would be of particular interest since the Wacker reaction provides the opposite regioisomer (A).  3.2.4 Aminohydroxylation and arylhydroxylation via TPArhodaoxetane The aminohydroxylation of olefins provides vicinal amino alcohols by the simultaneous incorporation of both a nitrogen and an oxygen. Aminohydroxylation of olefins via 2-rhodaoxetanes (Scheme 3-5, Eq. 2) would be an improvement over existing methods that involve expensive and toxic osmium reagents or radicals, both of which lack regiocontrol. 120'121 There are numerous other methods for producing vicinal amino acids from olefins, most significant among them are ring-opening reactions of either epoxides or aziridines. 122 Each of these transformations involves two reactions: first the epoxidation or aziridination of the appropriate olefin, then nucleophilic ring opening by a nitrogen or oxygen nucleophile, respectively. Regioselectivity is the dominant issue for 68  both of these ring-opening reactions since either of the two carbons in the epoxide or aziridine can be targeted by the nucleophile. Aminohydroxylation via 2-rhodaoxetanes would be mechanistically different from existing methods and is expected to yield vicinal amino alcohols chemoselectively. Changes made to the auxiliary ligands may effect regiocontrol over these reactions since the regiochemistry is determined at the oxidation step. The eventual use of chiral ligands for this reaction has the potential to provide greater stereocontrol over the products. Arylhydroxylation of olefins via 2-rhodaoxetane intermediates (Scheme 3-5, Eq. 3) would constitute a novel method for simultaneous incorporation of a hydroxyl and an aryl group and potentially also vinyl and alkyl moieties. Scheme 3-6 shows a proposed mechanism of the insertion reaction of acetone into TPA-rhodaoxetane XIII, followed by analogous mechanisms for the addition reactions we planned to develop with amines and organometallic reagents. The reactivity of TPArhodaoxetane XIII towards electrophiles has been demonstrated and is driven by the strongly nucleophilic character of the 2-rhodaoxetane oxygen. 79 We plan to exploit this reactivity for the development of two new reactions, aminohydroxylation and arylhydroxylation of olefins via metallaoxetanes. These transformations will require the successful ring-opening of the 2-rhodaoxetane by a chosen substrate followed by reductive elimination of the product from rhodium.  69  ^ ^  L 0LRh --1^, Rh  ^).,....._.... _,^o R2  --)`0 9  , , c;), Ni ...______[..Ri  LRh 1 -'0H - - - - -.- LRh + R2N R2N  OH  R LRh—i LRh ■,0NA _ _ - _ LRh + R •. (:)NA ^pJ ^ R L = TPA  Scheme 3-6 Mechanisms for the reactions of TPA-rhodaoxetane XIII with acetone, amines and organometallics  Hayashi and coworkers have achieved the Rh-catalyzed 1,4-addition of aryl and alkenylboronic acids to enones and certain other a,(3-unsaturated compounds, shown in Scheme 3-7. 123-125 This highly successful transformation involves the transmetalation of the aryl or alkenylboronic acid with a Rh-0 bond (both rhodium hydroxides and alkoxides). This transmetalation step is mechanistically analogous to the first step shown of our proposed reaction of TPA-rhodaoxetane XIII with an organometallic substrate in Scheme 3-6 above. RB(OH)2  ^  B(OH)3  L n Rh—OH^L Rh—R  EWG^  R  EWG^+ H2O  R = aryl or alkenyl group  Scheme 3-7 Rh-catalyzed 1,4-addition reaction  70  3.3 Results and Discussion TPA-rhodaoxetane XIII is of central importance to this study. All of our proposed reactions for study involve TPA-rhodaoxetane XIII or possibly a related rhodaoxetane species. Our initial plan was to first prepare TPA-rhodaoxetane XIII according to known methods, then use this complex to explore the proposed olefin functionalization reactions, as described in Section 3.2.  3.3.1 Preparation of TPA Tris[(2-pyridypmethyl]amine (TPA) 21 was prepared following the literature method. 126 In the literature procedure TPA 21 was purified by distillation under vacuum. Our attempts to purify TPA 21 by this method were unsuccessful, perhaps because the strength of the vacuum available to us was much higher than the one used in the literature procedure and this made the distillation difficult to control. An alternative method was developed using an unusual extraction method with water and acetone. The crude TPA 21 was dissolved in a minimal quantity of acetone. The concentrated acetone solution was decanted off of any undissolved material. Sufficient distilled water was added to the concentrated acetone solution to approximately double the total volume. The mixture formed two layers; the top layer was pale yellow and cloudy and the bottom layer was tarry orange-brown. The upper layer was decanted and dried to yield pure TPA crystals. The bottom layer contained TPA 21 and impurities. This extraction could be repeated on the dried bottom layer to yield several batches of highly pure TPA 21, as determined by 1H  NMR spectroscopy.  3.3.2 Preparation of [(q 2 -ethene)(K4 -TPA)Rh i r BP114  The rhodium ethylene complex, [(r) 2 -ethene)(1(4 -TPA)Rh Ir BPh4 " XII, was  71  prepared following the procedure published by de Bruin et al. 78 De Bruin reports a yield of 59% for this complex and our best yield was 53%. They filter the solution away from the precipitated product but otherwise do not report any purification steps.  3.3.3 Preparation of TPA-rhodaoxetane Three methods for preparing TPA-rhodaoxetane XIII were explored. The first two methods were published by de Bruin et a/. 78 ' 8° and involve the use of hydrogen peroxide to oxidize the TPA-rhodium ethylene complex XII. The third method uses nitrous oxide as the oxidant. None of these methods produced TPA-rhodaoxetane XIII reliably and in all three cases the yields were very low. Attempts to isolate TPArhodaoxetane XIII invariably led to a loss of the product, presumably due to decomposition. 3.3.3.1 Preparation of TPA-rhodaoxetane by hydrogen peroxide oxidation  De Bruin et al. report two methods for the preparation of TPA-rhodaoxetane XIII by oxidation of [(1 2 -ethene)(1c4 -TPA)Rhir XII with hydrogen peroxide. The first method uses isolated [(1 2 -ethene)((4 -TPA)RhT XII that was prepared previously. 78 The second method involves the direct preparation of TPA-rhodaoxetane XIII from [(11 2 -ethene)(K4 TPA)Rh ir XII prepared in situ and directly oxidized by hydrogen peroxide. 8° By the first method we prepared [(TPA)Rh ill(c2 -C,0-2-oxyethyl)] + BP114 - XIII from [(r1 2 -ethene)(x4 -TPA)RhT BPh4 - XII. According to the published procedure, [(ii ethene)(x 4 -TPA)Rh ir BPh4 - XII is used as it was prepared, with no additional purification steps. Our reaction was done on a very small scale in an NMR tube. The product was immediately analyzed by I li NMR spectroscopy, which matched the data published by de Bruin et al. 78 Attempts to isolate the product were unsuccessful so this  72  technique was used to prepare fresh TPA-rhodaoxetane XIII samples to be used directly in other reactions of interest. Attempts to prepare TPA-rhodaoxetane XIII by this method on the larger scale, as published, were wholly unsuccessful for us. TPA-rhodaoxetane XIII was also prepared directly from TPA 21 and [{RI-1(1C1)(ethene)212] XI starting materials according to the second protocol published by de Bruin et a1. 8° In this case the ethylene complex XII was not isolated but was directly oxidized by H202 to TPA-rhodaoxetane XIII. The rhodaoxetane precipitated with NaBPh4 or KPF6 to give yellow powder. Analysis of this product by 1 H NMR spectroscopy showed that a small amount of the desired product formed in low purity. To isolate TPA-rhodaoxetane XIII, attempts were made to recrystallize the product from a CH2C12 solution layered with pentane. Only a fine yellow precipitate formed by this method and analysis of this precipitate and the solution by 1 H NMR spectroscopy showed no remaining TPA-rhodaoxetane XIII. 3.3.3.2 Background reaction of TPA with hydrogen peroxide  A reaction between TPA 21 and hydrogen peroxide was performed in order to determine whether these two species underwent any side reaction during the oxidation of [(i 2 -ethene)(K4 -TPA)Rh Ir XI. If any such reaction between TPA 21 and H202 were to occur it would compete with the desired oxidation reaction and it might also contribute to the decomposition of the rhodium complexes in solution. TPA 21 (50 mg) and H202 (10.0 pL of a 35% aqueous solution) were combined with CDC1 3 (0 6 mL) in an NMR tube. A 1 H NMR spectrum of the reaction mixture showed no evidence of any reaction occurring.  73  3.3.3.3 Preparation of TPA-rhodaoxetane by nitrous oxide oxidation  A third protocol for preparing rhodaoxetane was inspired by the work of Hillhouse and coworkers where nitrous oxide was used to prepare an oxanickelacycle by oxygen insertion into a nickelacyclopentane ring. 108 In a 25 mL Schlenk flask equipped with a stir bar and a septum, 0.070 g of [(1 -1 2 -ethene)-(x4 -TPA)R0 + BPI14 - XII was dissolved in approximately 20 mL of dry benzene. Nitrous oxide was bubbled through the solution for 10 minutes while stirring. The benzene was removed by Schlenk line vacuum and the crude product was dissolved in approximately 0.5 mL of acetone-d6 and placed in an NMR tube. A 1 1-1 NMR spectrum showed peaks corresponding to TPA-rhodaoxetane XIII.  Although small amounts of TPA-rhodaoxetane XIII were observed by 1 H NMR spectroscopy, none of the aforementioned techniques were reliable. On many occasions these procedures yielded no observable TPA-rhodaoxetane XIII product. When TPArhodaoxetane XIII was prepared successfully the yield was very low and the product could not be isolated.  3.3.4 Reactions of TPA-rhodaoxetane Test reactions were performed using samples of TPA-rhodaoxetane XIII, generated in situ in an NMR tube from {(11 2 -ethene)(K4 -TPA)Rh ir XII and H202 in acetone-d6. Each of these samples was prepared in an NMR tube equipped with a septum so that H202 could be added by syringe and later a solution of a chosen substrate could be added by syringe to the fresh TPA-rhodaoxetane XIII The substrates chosen for study were aniline 23, toluenesulfonamide 24, phenylboronic acid 25 and benzaldehyde 22. In every case, the sample was observed by 1 1-1 NMR spectroscopy over a number of days. For all cases, 1 1-I NMR peaks corresponding to TPA-rhodaoxetane XIII are observed to 74  grow in for approximately the first 2 h. After that time, these peaks steadily decline over the next hours and up to several days, until none is observable in the spectra. For all of these examples, the 1 H NMR signals for the chosen substrates remain steady over the duration of the experiment. In each case, 1 H NMR signals of unknown species develop over time. The amounts of these products are very small in each case and it was not possible to identify or isolate these products. 3.3.4.1 Background reaction of benzaldehyde with hydrogen peroxide  It is known that TPA-rhodaoxetane XIII reacts with acetone, however this reaction occurs relatively slowly, taking approximately 2 weeks at room temperature. 79 It was thought that benzaldehyde 22 might react with the residual H202 in solution since over time benzaldehyde 22 reacts with air to form benzoic acid. To test whether such a reaction might be occurring, small amounts of benzaldehyde 22 and H202 were combined with CDC1 3 in an NMR tube. The reaction mixture was monitored by 1 H NMR spectroscopy for 8 h and showed no evidence of any reaction occurring. The main difficulty with the trial reactions with TPA-rhodaoxetane XIII was that the method for generation of TPA-rhodaoxetane XIII was not reliable. The quantity of TPA-rhodaoxetane XIII in the sample was very small and probably not the same for each sample. The amount of each substrate that was added was much greater than the amount of TPA-rhodaoxetane XIII in the sample. If the substrate was reacting with TPArhodaoxetane XIII, the amount was not sufficient to be observable with any significance. It was our intention to repeat these reactions with more rigorous experimental technique when the generation of TPA-rhodaoxetane XIII became more reliable. In the meantime, these reactions do not lead us to any conclusion about the reactivity of TPA-rhodaoxetane  75  XII I.  3.4 Summary TPA-rhodaoxetane XIII was prepared according to two procedures published by de Bruin et a/. 78 ' 8° with limited success. A third preparation method was explored involving the use of N20 as oxidant; however, only trace amounts of TPA-rhodaoxetane XIII formed by this method. Despite great time and effort directed towards this goal we  never achieved adequate purity or quantity of TPA-rhodaoxetane XIII Our difficulty producing TPA-rhodaoxetane XIII limited our ability to explore the scope of the reactivity of this complex. A few test reactions were performed using trace amounts of impure TPA-rhodaoxetane XIII combined with a selection of substrates. The large amount of impurity in the samples obscured our analysis, making any results difficult to interpret. It was apparent that TPA-rhodaoxetane XIII was disappearing from the samples, possibly because it reacted with the introduced substrate in each case. We are continuing our pursuit of this research into TPA-rhodaoxetane XIII reactivity.  3.5 Experimental Procedures 3.5.1 General Methods Manipulation of metallic compounds was performed using standard Schlenk techniques under an atmosphere of dry nitrogen or in a nitrogen-filled Vacuum Atmospheres or. MBraun glovebox ([02] < 2 ppm). NMR spectra were recorded on Bruker Avance 300 or Bruker Avance 400 spectrometers. Benzene was dried by passage through solvent purification columns. 119 CDC13 was vacuum-transferred from P2O 5 and degassed prior to use. Acetone-d6 was distilled from CaSO4 and degassed prior to use. Toluene-d8 was degassed prior to use. All other reagents and solvents were obtained from 76  commercial sources and used as received. 1 H and 31 P { 1 11} NMR spectra are reported in parts per million and were referenced to residual solvent. Coupling constant values were extracted assuming first-order coupling. All spectra were obtained at 25 ° C, unless otherwise stated. 3.5.1.1 Preparation of tris [(2-pyridypmethyl] amine (TPA) 21  o  L,  N  )-.„11■1H2 + 2  aq. NaOH  .  N N  19  ^  20^  21  TPA 21 was prepared following a modified literature method. 126 2(Aminomethyppyridine 19 (8 mL, 80 mmol) was added dropwise to a solution of 2picolyl chloride 20 (25.6 g, 160 mmol) in distilled water (40 mL) in a 250 mL round bottom flask equipped with a magnetic stir bar and a stopper, under a flow of  N2. The  reaction mixture turned red after several minutes of stirring. Sodium hydroxide (31 0 mL of a 10 M solution, 320 mmol) was added at a rate of approximately 5 drops/minute, controlled by an addition funnel. The flask was placed in an oil bath set to 70 °C for 30 minutes. The flask was removed from the heat source and cooled to room temperature. The resulting dark red oily suspension was extracted with CH2C12 (3 x 125 mL) using a separatory funnel. The combined extracts were dried over Na2SO4. The mixture was filtered and the solvent removed by Schenk line vacuum. The crude product was placed in a vial and partially dissolved in a very small quantity of acetone to form a viscous layer of solution over the tarry sediment. This solution was decanted away from any undissolved material. An approximately equal volume of distilled water was added to the 77  decanted solution. The resultant mixture formed two layers. The cloudy yellow top layer was decanted and dried to yield pure TPA 21 crystals. The orange-brown bottom layer contained TPA 21 and impurities. This extraction could be repeated on the dried bottom layer to yield several batches of highly pure TPA 21. Yield: 3.60 g (16%). 1 H NMR (CDC13, 300 MHz) S 8.52 – 8.50 (m, 3 H), 7.66 – 7.54 (m, 6 H), 7.14 – 7.10 (m, 3 H), 3.87 (s, 3 x 2 H, CH2). The product identity was confirmed by comparing the 1 H NMR spectrum with reported data. 126 3.5.1.2 Preparation of [(11 2-ethene)(K 4-TPA)Rh 11 + BPh4 XII  rN  BPh4  [{Rh(p-CI)(C2H4)2}2] XI N NMe0H, -78 °C NaBPh4 21  ^  XII  TPA 21 (30 mg, 0.104 mmol) and [{Rh(g-C1)(ethene)212] XI (20 mg, 0.05 mmol) were placed together in a 15 mL Schlenk flask equipped with a magnetic stir bar and stopper under N2 in a glovebox. The flask was removed from the glovebox and placed on a N2 filled Schlenk line, following standard Schlenk techniques to avoid contamination with air or moisture. Anhydrous methanol (5 mL) was added to the flask by cannula. The mixture was cooled to -78 °C in a CO2/acetone bath and stirred for 1 h. The solution was added to a second 15 mL Schlenk flask containing NaBPh4 (164 mg, 0.48 mmol). Some of the solvent was removed by vacuum and a fine yellow-green precipitate formed. The mixture was filtered through a sintered glass funnel and the yellow-green powder was dried under vacuum. Yield: 0.034 g (53%). The product identity was confirmed by comparing the 1 1-1 NMR spectrum with reported data.78 78  3.5.1.3 Preparation of [(TPA)RW II (K2-C,0-2-oxyethyl)r BPh4 XIII (by oxidation of [(n 2 -ethene)(e-TPA)Rh ir BPh4 XII with H202)  1 a N,  H202 1  -N  —  Rh" —N- I  -10°C  XII  H20  XIII  [(1 2 -ethene)(K4 -TPA)Rh(I)] + BPh4 - XII (0.034 g, 0.0053 mmol) and acetone-d6 (0.6 mL) were placed in an NMR tube equipped with a septum under N2 in a glovebox. The tube was removed from the glovebox. Hydrogen peroxide (5.0 pL of a 35% aqueous solution) was added through the septum by syringe. The NMR tube was inverted repeatedly to mix the contents. The solution was cooled to -10 ° C in an ice bath for 1 h before collecting the NMR data. The product identity was confirmed by comparing the 1H  NMR spectrum with reported data. 78  3.5.1.4 Preparation of [(TPA)Rh in (K2_ C,0-2-oxyethyl)r BPh4 XIII (by oxidation of [(11 2 -ethene)(K 4 -TPA)Rh ir BPh4 XII with N20)  N2.^  N  N2  1 XII  I  XIII  [(11 2 -Ethene)(1(4 -TPA)RhI l- BPh4 XII (70 mg, 0.11 mmol) and benzene (approximately 20 mL) were placed in 25 mL Schlenk flask equipped with a septum and a magnetic stir bar. The Schlenk flask was removed from the glovebox. Nitrous oxide was bubbled through the solution for 10 minutes using a needle inserted through the septum. A second needle was inserted through the septum to provide an exhaust for 79  excess pressure. The benzene was removed by Schlenk line vacuum and the crude product was redissolved in acetone-d6 (approximately 0.5 mL) and placed in an NMR tube for analysis. The 1 1-1 NMR spectrum showed the appearance of new peaks indicating a trace amount of product. The product was not identified and further attempts at this reaction were no more successful. 3.5.1.5 Background reaction of TPA 21 with H202  ONc rre  H202  no reaction  21  TPA 21 (50 mg, 0.17 mmol) and CDC13 (0 6 mL) were placed in an NMR tube equipped with a septum. A syringe was used to add H202 (10.0 pi, of a 35% aqueous solution) and the tube was inverted repeatedly to mix the contents. A 1 1-1 NMR spectrum of the mixture was obtained and showed no evidence of any reaction occurring. 3.5.1.6 Background reaction of benzaldehyde 22 with H202 0 Ph)LH +  n  I-I -22^  no reaction  22  Small amounts of benzaldehyde 22 (a drop) and hydrogen peroxide (a few drops of a 35% aqueous solution) were combined in an NMR tube with approximately 0.5 mL CDC13. The reaction mixture was monitored by 1 1-1 NMR spectroscopy for 8 h and showed no evidence of any reaction occurring.  80  3.5.1.7 Reaction of [(TPA)Rh ill (K2 -C,0-2-oxyethy1)1 + XIII with aniline 23 -1 +  fett 3 Re"^NH2 —N 0 XIII 23  unidentified trace product  A fresh sample of RTPA)RII III0c2 -C,0-2-oxyethypr XIII was prepared in an NMR tube by dissolving a small quantity of [0-1 2 -ethene)(K4 -TPA)Rh 1] + XII in approximately 0 5 mL of acetone-d6. H202 (5.0 [LI, of a 35% aqueous solution) was then added by syringe through a septum in the NMR tube cap. The formation of [(TPA)Rh m (c2 4-2,0-2-oxyethy1)} ± XIII was confirmed by comparing the 1 H NMR spectrum with reported data. 78 A small amount of aniline 23 (5.0 1.1L, 0.055 mmol) was added to the TPA-rhodaoxetane XIII sample by syringe. The sample was kept cool in an ice water bath for 30 minutes prior to analysis. The solution was monitored by 1 H NMR spectroscopy over 3 days. Trace reaction was observed in the 1 H NMR spectra and no products were identified. 3.5.1.8 Reaction of RTPA)Rh m (K2 -C,0-2-oxyethyl)] + XIII with toluenesulfonamide 24 02  N  S,  N Roi- s — \^+ —ts1 I ....--^0..  . I ^r  N H2  ..  unidentified trace product  -  l  XIII  24  A fresh sample of [(TPA) Rhin (1C2- C,0-2-oxyethy1)1 + XIII was prepared in an NMR tube by dissolving a small quantity of [(r1 2 -ethene)((4 -TPA)Rh 1r XII in approximately 0.5 mL of CD2C12. H202 (5.0 pL of a 35% aqueous solution) was then 81  added by syringe through a septum in the NMR tube cap. The formation of RTPA)Rh111 ec2 -C,0-2-oxyethypr XIII was confirmed by comparing the I I-I NMR spectrum with reported data. 78 A small amount of toluenesulfonamide 24 (10.0 pL of an approximately 100 g/L CD2C12 solution) was added to the TPA-rhodaoxetane XIII sample by syringe. The sample was kept cool in an ice water bath for 20 minutes prior to analysis. The solution was monitored by 1 HNMR spectroscopy over 3 days. Trace reaction was observed in the 1 1-1 NMR spectra and no products were identified. 3.5.1.9 Reaction of [(TPA)Rh III (K2-C,0-2-oxyethy1)1 + XIII with phenylboronic acid 25  B4  OH  unidentified trace product  OH 25  A fresh sample of [(TPA)Rh 111(c2 -C,0-2-oxyethyl)] + XIII was prepared in an NMR tube by dissolving a small quantity of [(1 2 -ethene)(x4 -TPA)Rh1r XII in approximately 0.5 mL of CD2C12. H202 (5.0 pi, of a 35% aqueous solution) was then added by syringe through a septum in the NMR tube cap. The formation of [(TPA)Rh C,0-2-oxyethyl)]+ XIII was confirmed by comparing the 1 I-1 NMR spectrum with reported data. 78 A small amount of phenylboronic acid 25 (10.0 pi, of an approximately 100 g/L CD2C1 2 solution) was added to the rhodaoxetane sample by syringe. The sample was kept cool for 1 h prior to analysis. The solution was monitored by 'H NMR spectroscopy over 3 days. Trace reaction was observed in the I I-I NMR spectra and no products were identified.  82  3.5.1.10 Reaction of RTPA)Rh ill (K2 -C,0-2-oxyethyl)r XIII with benzaldehyde 22  N^  N1 N  iTD s -- \ + PhAH  Q  RO  -  0  —  unidentified trace product  -  XIII^  22  A fresh sample of [(TPA) RhIII(1(2_ C,0-2-oxyethypr XIII was prepared in an NMR tube by dissolving a small quantity of [(1 2 -ethene)(K4 -TPA)Rh ir XII in approximately 0 5 mL of acetone-d6. H202 (5.0 1.1L of a 35% aqueous solution) was then added by syringe through a septum in the NMR tube cap. The formation of RTPA)Rhili(K2 -C,0-2-oxyethyl)1 + XIII was confirmed by comparing the 1 1-1 NMR spectrum with reported data. 78 A small amount of benzaldehyde 22 (10.0 of a 100 1.1L/g acetone solution) was added to the TPA-rhodaoxetane XIII sample by syringe. The solution was monitored by 1 1-1 NMR spectroscopy at 15 min, 30 min, and 1 h. Trace reaction was observed in the 1 H NMR spectra and no products were identified.  83  4 Summary, conclusions and future work 4.1 Summary The development of reactions that lead to selectively functionalized products from simple and readily available olefins and alkynes is an active area of research. Much of the focus of study is directed toward transition metal complexes for their potential as catalysts for these reactions. The research presented in this thesis regards the reactivity of Rh-P and Rh-0 bonds in rhodium complexes with multidentate nitrogen donor ligands. This thesis is comprised of two subprojects: one exploring P-H bond activation by pyrazolylborate rhodium complexes and the other on developing olefin functionalization reactions via 2-rhodaoxetane intermediates.  4.1.1 Hydrophosphinylation catalyzed by pyrazolylborate rhodium complexes The pyrazolylborate rhodium complexes [Tp*Rh(PPh 3 )2 ] III and [Tp*Rh(cod)]2 IV were compared with known catalysts for their activity in the hydrophosphinylation of  1-alkyne 2 with diphenylphosphine oxide 1. These Tp*RhL i, complexes demonstrated moderate activity and high regioselectivity for the E-linear vinylphosphine oxide product from this reaction; however, they were not as active as the known catalysts [C1Rh(PPh3)2] I and [C1Rh(cod)]2 II. The activity of [Tp*Rh(PPh3)2] III was then evaluated for hydrophosphinylation of a range of alkyne substrates. In each case, the E-linear vinylphosphine oxide resulting from syn-addition of P-H across the alkyne bond formed as the exclusive product. Higher yields were provided by aliphatic alkynes than aromatic alkynes and the highest yield was obtained for an internal aliphatic alkyne. Product formation may be directed by the steric bulk of the ligands on rhodium. An investigation  84  was made into the mechanism of hydrophosphinylation catalyzed by Tp RRhLn complexes. 1 H and 31 P NMR spectroscopic evidence suggests that hydrophosphinylation catalyzed by pyrazolylborate rhodium complexes follows an analogous mechanism to that proposed by Han et al. for hydrophosphinylation by [C1Rh(PPh3)3] I or [C1Rh(cod)]2 II.  4.1.2 Direct functionalization of olefins via 2-rhodaoxetanes TPA-rhodaoxetane XIII has been shown to be readily generated and isolable, yet reactive toward a number of substrates. 79 TPA-rhodaoxetane XIII could potentially be used as an intermediate for a number of mechanistically novel olefin functionalization reactions. Three methods for preparing TPA-rhodaoxetane were pursued with limited success. Two published procedures were followed that each provided small quantities of impure TPA-rhodaoxetane. 78 ' 8° A third method involved oxidation of [(r1 2 -ethene)(ic 4  -  TPA)RhIr BPh4- XII by N20; however, only trace amounts of TPA-rhodaoxetane XIII formed as observed by 1 H NMR spectroscopy. Test reactions were performed with what little amount of TPA-rhodaoxetane XIII was available combined with a selection of substrates. These test reactions do not lead to any conclusions about the reactivity of TPA-rhodaoxetane since the large amount of impurity in the samples interfered with the analysis of any results.  4.2 Future work Metal-heteroatom reactivity, including reactions involving Rh-P and Rh-0 bonds, will continue to be explored through many ongoing research projects in the Love group. In particular regard to this thesis work, the project involving the development of olefin functionalization reactions via 2-rhodaoxetanes is being continued by a Ph.D. student,  85  Alexander Dauth.  4.2.1 P-H bond activation reactions catalyzed by pyrazolylborate rhodium complexes In this thesis the ability of pyrazolylborate rhodium complexes to catalyze the hydrophosphinylation of alkynes has been established. Future investigations will endeavor to provide more reactive Tp RRhLn catalysts for this reaction. Substituents on the pyrazolyl groups of Tp R ligands can be varied such that the steric and electronic features of the resulting complexes might bring about more efficient catalysis. Efforts will be made to further expand the scope of this reaction to other types of P-H sources and a wider range of alkyne substrates.  4.2.2 Functionalization reactions of olefins via 2 rhodaoxetanes -  Finding a reliable method for generating TPA-rhodaoxetane XIII will be a crucial initial goal for the future success of this project. Once TPA-rhodaoxetane XIII is available in reasonable yield and purity, the development of the reactions proposed in this thesis will be pursued. Any reactions that are developed can then be explored for their potential regio- and enantioselectivities when substituted olefins are used in place of simple ethylene.  4.2.2.1 Enantioselectivity of olefin functionalization reactions via 2 rhodaoxetanes -  2-Rhodaoxetane intermediates with chiral ligands could be used to develop enantioselective versions of oxidation, aminohydroxylation, and carbohydroxylation. The metal center should strongly influence the enantioselectivity-determining step of these reactions. Scheme 4-1 shows examples of how 2-rhodaoxetane intermediates might be used for enantioselective syntheses. Equation 1 in Scheme 4-1 shows how chiral aldehydes might be prepared from 1,1-disubstituted olefins. Equation 2 would likely lead 86  ^  to a stable 0-disubstituted rhodaoxetane since at least one 0-hydrogen would be necessary for the elimination of a carbonyl-containing compound from this complex. 1,2Disubstituted olefins would lead to products with two stereocenters. Equation 3 depicts the potential formation of enantiomers by aminohydroxylation and likewise, Equation 4 would potentially provide enantiomers from aryl or alkylhydroxylation. R1 R 2 L n Rh L n Rh ^ R` L n Rh^ ^  0  O  R1  R2  H202  ^  L n Rh  H202  LnR1?—  o  1,1-disubstituted olefins  'R a .2  l  NH 2 R 3 R OH R1  L n Rh  Ri  H202 R 2 B(OH)2 4 ^ R  1, 2-disubstituted olefins  R2  OH  Scheme 4 1 Possible outcomes of the proposed functionalization reactions with either 1,1- or 1,2-disubstituted olefins -  87  References (1) Lautens, M.; Roy, A.; Fukuoka, K.; Fagnou, K.; Martin-Matute, B. J. Am. Chem. Soc. 2001, 123, 5358-5359. (2) Heck, R. F.; Nolley, J. P., Jr. J. Org. Chem. 1972, 37, 2320-2322. (3) RajanBabu, T. V. Chem. Rev. 2003, 103, 2845-2860. (4) Caballero, A.; Sabo-Etienne, S. Organometallics 2007, 26, 1191-1195. (5) Hegedus, L. S.; Williams, R. E.; McGuire, M. A.; Hayashi, T. J. Am. Chem. Soc. 1980, 102, 4973-4979. (6) Lachaize, S.; Sabo-Etienne, S.; Donnadieu, B.; Chaudret, B. Chem. Comm. 2003, 2, 214-215. (7) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483. (8) Morrill, C.; Grubbs, R. H. J. Org. Chem. 2003, 68, 6031-6034. 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Synth. 1998, 32, 70-75.  94  Appendix I: NMR spectra  39^38^37^36^35^34^33^32^31^30^29^28^27^26^25 Chemical Shift (ppm)  31 P^NMR  (C6D6, 121 MHz) spectrum of (E)- 1-(diphenylphosphiny1)-2-(4methoxyphenypethene 10  95  9.5^9.0^8.5^8.0^7.5^7.0^6.5^6.0^5.5^5.0^4.5^4.0^3.5^3.0^2.5^2.0^1.5^1.0^0.5 Chemical Shift (ppm)  H NMR (C6D6, 300 MHz) spectrum of (E)-3-(diphenylphosphiny1)-3-hexene 11  140^130^120^110^100^90^80^70^60^50^40^30^20^10^0 Chemical Shift (ppm)  13 C  NMR (C6D6, 75 MHz) spectrum of (E)-3-(diphenylphosphiny1)-3-hexene 11  96  34.5^34.0^33.5^33.0^32.5^32.0^31.5^31.0^30.5^30.0^29.5^29.0^28.5^28.0^27.5^27.0^26.5^26.0^25.5^25.0 Chemical Shift (ppm)  31  F' { 1 H} NMR (C6D6, 121 MHz) spectrum of (E)-3-(diphenylphosphiny1)-3-hexene 11  97  17.297.287.277.287.257 287.287.217.217.207.187.187.177.107.157.187.187.187.11 ^ Chemical Shift (ppm)^  -14.05^-14.10^-14.15^-14.20^-14.25^-14.30^-14.35^-14.40^-14.45 Chemical Shift (ppm)  NMR (C6D6, 400 MHz) spectrum of complex IX  116^114^112^110^108^108^104^102^160 Chemical Shift (ppm)  31  1{ 1 H} NMR (C6D6, 162 MHz) spectrum of complex IX  98  17.15 17.10 17.05 17.00 16.95 16.90 16.85 1( Chemical Shift (ppm)  -14.05 -14.10 -14.15 -14.20 -14.25 -14.30 -14.35 -14.40 -14.45 Chemical Shift (ppm)  skl,„4,iluk 4.0  3.5^  1  3.0^ 2.5^ Chemical Shift (ppm)  2.0^  115^  H NMR (C6D6, 400 MHz) spectrum of complex X  99  110^ 0.5  114^112^110^108^108^104^102^100^98^98^94^92^90^88^86^84^82^80 Chemical Shift (ppm)  31p eHI NMR (C6D6, 162 MHz) spectrum of complex X  100  9.5^9.0^8.5  8.0^7.5^7.0^8.5^8.0^5.5^5.0^4.5^4.0^a5^a0^2.5^ Chemical Shift (ppm)  1H  NMR (CDC13, 300 MHz) spectrum of TPA 21  101  2.0^1.5^1.0^0.5^0  

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