Configurational Stability and Transfer of Stereochemical Information in the Reactions of Enantioenriched Organolithium Reagents

Graphical Abstract

Chiral organolithium compounds are versatile intermediates with numerous applications in asymmetric synthesis. They range widely in their configurational stability and in the stereochemistry of their electrophilic substitution. Effective transfer of stereochemical information from the lithiated intermediate (C1 and epi-C1) to the final product (P1 and ent-P1) is dependent on the interplay between these two factors.

Abstract

The conversion of a prochiral methylene group into a stereogenic center by means of a lithiation/substitution sequence has emerged as a powerful synthetic transformation over the past 15 years. This reaction proceeds via a chiral organolithium intermediate, and the stereochemical fidelity of the overall reaction sequence is intimately dependent on the stereochemical behavior of the chiral organolithium as well as on the rate and stereochemical sense of the electrophilic substitution step. Chiral organolithium reagents were first reported by Letsinger, Curtin, and Applequist half a century ago. The lithiated intermediates in these early studies were not highly configurationally stable, and applications in stereoselective synthesis were not immediately forthcoming. The two decades that followed the 1980 report by Still and Sreekumar of a configurationally stable α-oxyorganolithium were marked by an increased interest in these reagents. As the synthetic applications of chiral organolithium reagents have grown, so have accompanying mechanistic studies of these intermediates which serve as the basis for this review.