Item – Theses Canada

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OCLC number
56065781
Link(s) to full text
LAC copy
LAC copy
Author
Belelie, Jennifer Lynne,1974-
Title
Stereoselective reactions of organocopper reagents with acyclic allylic substrates.
Degree
Ph. D. -- University of Waterloo, 2002
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, [2003]
Description
3 microfiches.
Notes
Includes bibliographical references.
Abstract
Four different approaches to copper-mediated, stereoselective S N2' reactions with acyclic substrates will be discussed. Each route was met with different degrees of success. The first strategy developed employed 1,3-chirality transfer from the site bearing the leaving group to the site of attack. Chirality was introduced to allylic alcohols via Sharpless kinetic resolution chemistry (typically >=90%ee). These compounds were transformed to phosphate esters. With these substrates, regio- and stereoselectivities of up to 98% were possible during the copper coupling reactions. The efficiency of these reactions was highly dependent upon the substrate and the cuprate structure. The best regio- and stereoselectivities were obtained with substrates bearing bulky groups at the [alpha]-position. Unfortunately, highly stereoselective cuprate additions were limited to primary alkyl and benzylic groups. The coupling reactions occurred with 'anti '-facial selectivity and retention of ('E')-double bond geometry. The next two routes employed Rossiter's cuprate to introduce chirality to the system. In the first approach, chiral cuprates were reacted with racemic allylic substrates, in hopes of alkylating one of the enantiomers and leaving the other one mostly unreacted (kinetic resolution). Unfortunately, all of the products recovered from these reactions were racemic. The second strategy used Rossiter's ligand in cuprate additions to prochiral substrates. The products recovered from these reactions were also racemic. The final strategy involved 1,2-chirality transfer. Primary, secondary, tertiary alkyl and phenyl groups were introduced to [delta]-alkoxy- and [delta]-silyloxy-substituted substrates with 'anti'-facial selectivities of >=96%. The outcomes of these reactions were highly dependent upon the structure of the substrates and the nature of the organocopper reagents. The best results were achieved with bulky groups, such as 'i'-Pr and Ph, on the site bearing the leaving group. The highest facial selectivities were achieved with CuCN-catalyzed Grignard reagents. It is hypothesized that the compounds react through a modified Felkin-Ahn conformation, in which the [delta]-oxy-substituent takes the role of the medium-sized group. This methodology was applied to non-racemic substrates to synthesize enantiomerically-enriched benzyloxy-substituted alkenes and alcohols. When the alkoxy- and silyloxy-substituents were replaced with hydroxyl groups, the facial selectivities of the reactions changed from 'anti ' to 'syn'. We believe that the reversal of selectivity is facilitated by formation of a mixed-cuprate species from the oxygen anion on the substrate and the incoming nucleophile. With the hydroxyl-substituted substrates, the selectivities of the reactions were directly proportional to the size of the group transferred from the cuprate. The highest facial selectivities were observed during 't'-Bu addition. In contrast to the alkoxy- or silyloxy-substituted systems, the best results were achieved with an 'n'-Bu group on the leaving group site. Under certain conditions, diastereoselectivities of >=98% were possible.
ISBN
0612772217
9780612772212