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UBC Theses and Dissertations

Chiral oxazolines in asymmetric synthesis and studies on the development of organosilicon reagents Hoy, Kevin


This thesis is divided into two chapters. Chapter I describes the synthesis of several novel chiral oxazolines and investigations of their utility in asymmetric synthesis. Oxazoline 58, prepared from L-PhenyIaIanine, and oxazolines 75, 76, 77 and 83 prepared from L-tyrosine, were subjected to a deprotonation-aIkyIation sequence. The diastereomeric excess of the alkylated oxazoline possessing the S-configuration at the α-chiral carbon was only modest (20-23%) as determined by ¹H nmr spectroscopy. The expected increase in diastereoselectivity, due to steric and chelation effects, with the modified oxazolines 23, 23, 12, and 83 was not observed. The second chapter deals with various aspects of the chemistry of organosiIicon compounds. Our attempts to develop a silicon-based protecting group for alcohols and amines met with only limited success. SuIfonyichloride 98, prepared from 4-chIorotoIuene, was converted to several sulfonates 99 and sulfonamides 100. The proposed deprotectlon by a fluoride-Induced fragmentation process does appear to proceed through a sulfene Intermediate. However, the success of the deprotection appears to be dependent on an anhydrous source of fluoride ion, the absence of internal proton sources, and stabilized leaving groups. A proposed deoxygenation method involving fIuorIde-induced fragmentation of siIanecarboxyIic esters was not successful. Treatment of esters 148 and 157 did not give any of the desired deoxygenation products octane and ⍜-nitrotoIuene, respectively, but Instead gave quantitative yields of 1-octanol and ⍜-nitrobenzyl alcohol. A general and convenient method of preparing siIanecarboxyIic acids has been developed. Ozonolysis of bissiIyIacetyIenes 139 in dichIoromethane at -24°C gives either the symmetric silyisiIanecarboxyIates 140 or siIanecarboxyIic acids 132 directly in cases where the sllyigroup is not sterically hindered. Silyisi IanecarboxyIates 140 are then readily converted by acid-catalyzed hydrolysis or methanolysls to siIanecarboxyIic acids. The kinetics of the thermal rearrangement of several siIanecarboxyIic esters in ⍜-dichIorobenzene to give the corresponding siloxanes were studied by monitoring the progress of the reactions by ¹H nmr spectroscopy. These first-order rearrangements are characterized by large free energies of activation of about 32 kcal/mole at 120°C. The thermolysis of siIanecarboxyIic acids has been determined to proceed by a different pathway to give only the corresponding silylformates. Acid-catalyzed alcoholysis of silylsiIanecarboxyIates and silylcarboxylates has been found to proceed by a silyI-oxygen cleavage mechanism. Kinetic studies showed that the acid-catalyzed hydrolysis of t-butyldImethyIsiIyI phenyIacetate is an overall third-order reaction. Only the Aal² mechanism is consistent with the results of both the chemical and kinetic studies. This result represents the first demonstration of carboxylic ester hydrolysis proceeding by the Aal² mechanism. [Formula Omitted]

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