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Title:Mechanistic studies of asymmetric induction at benzylic centers of organolithium species
Author(s):Lee, Steven Paul
Doctoral Committee Chair(s):Beak, Peter
Department / Program:Chemistry
Discipline:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Chemistry, Organic
Abstract:The mechanisms of asymmetric induction involving the lithiation and substitution of N-benzyl-N-Boc-N-p-methodically amine and N-benzyl-N-Boc-N-3-chloropropyl amine were investigated and are reported here. These two substrates undergo deprotonation with butyllithium in the presence of the chiral ligand (${-}$)-sparteine to generate their benzyllithium intermediates, which are subsequently reacted with electrophiles to yield highly enantioenriched products. For N-benzyl-N-Boc-N-3-chloropropyl amine, the electrophile is a part of the substrate, so the reaction is an intramolecular cyclization.
The enantioselectivity in these reactions can arise either during or after the deprotonation of the substrate. These two limiting possible mechanisms were distinguished by comparing the results of the reaction following the replacement in the substrate of one of the two prochiral, benzylic hydrogens for a deuterium. For both of these reactions, the enantioselectivity was shown to occur during the deprotonation of the substrate.
The intramolecular cyclization of N-benzyl-N-Boc-N-3-chloropropyl amine was further studied by negating the possibility of asymmetric substitution. A racemic sample of the benzyllithium intermediate was generated from its racemic stannyl analog within the presence of (${-}$)-sparteine, which cyclized revealingly into racemic product.
Moreover, the benzyllithium intermediate generated from lithiation of N-benzyl-N-Boc-N-p-methoxyphenyl amine was shown to be configurationally stable by evaluating the dependence of the enantioselectivity upon the extent of the substitution step. Other observations involving the $\alpha$-deuterated analog were consistent with a mechanism where the lithiated intermediate accelerates the rate of the lithiation. The configurational stability of N-($\alpha$-lithio-$\alpha$-methyl) benzyl-N-Boc-N-p-methoxyphenyl amine, a tertiary benzyllithium derivative, was also tested by generating an enantiopure sample of this benzyllithium intermediate from its enantiopure stannyl analog. This tertiary benzyllithium derivative was determined to be configurationally stable.
Additional benzyllithium species were tested for their configurational stability by reacting them with chiral electrophiles and comparing the diastereoselectivities of the reaction. The results with N,N-diisopropyl-o-$(1\prime$-lithioethyl)benzamide were consistent with a configurationally labile species. The tests on N,3-dilithio-N-methyl-3-phenylpropanamide and o-ethyl-N,$\alpha$-dilithio-N-pivaloylaniline led to inconclusive results.
Issue Date:1996
Type:Text
Language:English
URI:http://hdl.handle.net/2142/19584
ISBN:9780591198782
Rights Information:Copyright 1996 Lee, Steven Paul
Date Available in IDEALS:2011-05-07
Identifier in Online Catalog:AAI9712346
OCLC Identifier:(UMI)AAI9712346


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