Dynamics of the Lithium Amide/Alkyllithium Interactions: Mixed Dimers and Beyond

This review summarizes detailed investigations on the enantioselective nucleophilic addition of organolithiums onto prochiral electrophilic substrates, one of the simplest reaction meant to create a C–C bond, using dipolar bimetallic systems. Interestingly, these very popular and useful chemical transformations, even if taught at the undergraduate level, have remained underdeveloped when it comes to their enantioselective versions. The systems we present consist of a nucleophilic organolithium (NuLi) in strong dipolar interaction with a second lithiated entity bearing the source of asymmetry, i.e., a chiral lithium amide (CLA) derived from a 3-aminopyrrolidine (3APLi). Several 1:1 3APLi/NuLi noncovalent mixed aggregates are described and their relevance to the enantioselective process is discussed. Since the Curtin–Hammett principle forbids to correlate the complexes to the final ee's of the products, we have run complementary experiments of which results led us to propose the participation of an ephemeral, but more reactive, triptych aggregate