Chapter I. The synthesis, conformational analysis and catalytic properties of four chiral (non-racemic) 4-substituted quinolizidines. Chapter II. Alkylation reactions of derivatives of the camphor-imine of t-butyl-glycine.
Date of Award
Chemistry and Biochemistry
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Chapter I. The synthesis of 4R, 10R, 11R, and 4S, 10R, 11S 4- (1-hydroxy-2-(benzyloxy)ethyl) quinolizidine (76a and 76b); and 4-(1,2-dihydroxyethyl)quinolizidine (78a and 78b) in enantiomerically pure form has been achieved. The chiral centers were established by formation of a chiral 2-substituted piperidine and cyclization of optically active epoxides. The solution conformation of these molecules (shown below) have been determined by 300 MHz proton NMR measurements. Amino alcohols 76a and 78a were found to exist in a trans-fused 6,6 ring junction whereas 76b and 78b were found to exist in a cis-fused 6,6 ring junction. The metal salts of diastereomeric quinolizidines 76a/76b and 78a/78b function as catalysts, providing opposing enantioselectivity in the diethyl zinc addition to benzaldehyde. Both 76a and 78a gave the S enantiomer of 1-phenyl-1-propanol in excess while 76b and 78b gave the R enantiomer in excess. The best result was obtained employing the lithium salt of 76a as a catalyst which produced a 98% chemical yield of S enantiomer in 84% enantiomeric excess. The R enantiomer was obtained in 58% enantiomeric excess and in 76% chemical yield employing the zinc salt of amino alcohol 78b as the catalyst.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) Chapter II. The norcamphor imine of t-butylglycinate was prepared and found to exist as a 5:1 ratio of geometric isomers at the imine double bond. Alkylation reactions of the corresponding lithium enolate with benzyl bromide proceed with no diastereofacial selectivity implying that the methyl groups are crucial to obtaining high diastereofacial selectivity in the corresponding camphor imine. The 10-hydroxymethylcamphor imine of t-butyl glycinate was prepared and found to exist as a single diastereomer at the imine double bond. Alkylation reactions of the corresponding dilithium enolate with benzyl bromide were found to give products with lower diastereofacial selectivity (de = 80%) compared to the corresponding camphor imine (de = 100%). Addition of hexamethyl phosphoramide caused an increase in the chemical yield but had little effect on the diastereofacial selectivity. This 10-hydroxymethylcamphor imine also undergoes aldol reaction with benzaldehyde. Source: Dissertation Abstracts International, Volume: 50-03, Section: B, page: 0927. Thesis (Ph.D.)--University of Windsor (Canada), 1989.
Matassa, Luca Carmine., "Chapter I. The synthesis, conformational analysis and catalytic properties of four chiral (non-racemic) 4-substituted quinolizidines. Chapter II. Alkylation reactions of derivatives of the camphor-imine of t-butyl-glycine." (1989). Electronic Theses and Dissertations. 1386.