The Alkylation of Carbanions

LDA and related, sterically hindered, lithium dialkylamides, first investigated by Levine [1], have completely replaced the more nucleophilic sodium amide, which had been the base of choice for many years [2], Because the reactivity of an organo-metallic compound depends to a large extent on its state of aggregation (i.e. on the solvent and on additives) and on the metal, transmetalation of the lithiated intermediates and the choice of different solvents and additives emerged as powerful strategies for fine-tuning the reactivity of these valuable nucleophiles. 

Side Reactions in Organic Synthesis. Florencio Zaragoza Dorwald Copyright 2005 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31021-5 

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Chiral crown ether phosphine-palladium complexes have been used to catalyse the alkylation of carbanions derived from a-nitro ketones and a-nitro esters,63 and proline rubidium salts have been used to catalyse asymmetric Michael addition of nitroalkanes to prochiral acceptors 64 80% enantioselectivity can be achieved in each case. 

Amino acid esters can be dimerized to dioxopiperazines, which are conveniently reduced with sodium borohydride,/titanium(IV) chloride to give the corresponding chiral piperazine derivatives. Thus, from valine and phenylalanine, useful auxiliaries 20 and 21 were obtained9, and used for the alkylation of carbanions (Section D. 1.1.1.3.1.) and as catalysts for the addition of zinc alkyls to aldehydes (Section D.1.3.1.4.), as well as for enantioselective deprotonation and elimination (Section C.). 

By reduction of the aromatic rings, the enantiomers of 1,2-dicyclohexyl-l, 2-ethanediol 14 are obtained, which have also found application for the alkylation of carbanions via a-haloboronic acids (Section D.1.1.2.1.). 

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