3-Aminopyrrolidine lithium amides as chiral ligands for alkyllithium derivatives: Synthesis, NMR analysis, and computational study of their mixed aggregates*

An overview of the role of 3-aminopyrrolidine lithium amides (3-APLi’s) as chiral ligands for alkyllithiums (AlkLi’s) is presented. Synthetic developments as well as NMR characterizations and computational interpretations have been simultaneously and complementarily conducted to improve the ligand design for a model reaction that is the condensation of AlkLi’s on o-tolualdehyde, for which enantiomeric excesses up to 80 % were obtained. This study describes the whole chain going from the synthesis of the chiral 3-aminopyrrolidines (3-APs) (18 different 3-APs synthesized) to the characterization of the noncovalent mixed aggregates resulting from the interaction between the organolithium partners (3-APLi:AlkLi). Finally, the docking of the aldehyde on one lithium of the aggregate was analyzed by theoretical means on simplified models, in an attempt to understand the structure of the fully loaded pretransition complexes.