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Updated: Jul 5, 2026

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents
Published on: November 12, 2016
Analysis of an asymmetric addition with a 2:1 mixed lithium amide/n-butyllithium aggregate
Jia Liu1, Deyu Li, Chengzao Sun
1Department of Chemistry, Brown University, Providence, RI 02912, USA.
Abstract:
A 2:1 lithium amide/ n-butyllithium aggregate 1 is investigated as an asymmetric addition template in hydrocarbon solvents. Several different chiral lithium amides were synthesized from l-valine and tested in the asymmetric addition of n-BuLi to various aldehydes. Enantiomeric excesses up to 83% were obtained in the case of the addition of n-BuLi to pivaldehyde at -116 degrees C in pentane. (1)H and (13)C INEPT DOSY were utilized to characterize a new trimeric complex 12 between 2 equiv of lithium amide and 1 equiv of lithium alkoxide. This mixed aggregate strongly indicates the possibility of product-induced chirality inhibition that is detrimental to the enantioselectivity of asymmetric addition reaction.
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