Enantioselective protonation and alkylation of non-covalent mixed aggregates of chiral 3-aminopyrrolidine lithium amides

Article abstract of DOI:10.1016/S0040-4020(02)00377-0

Non-covalent aggregates of highly polar entities assemble, on a temporary basis, a chiral moiety to a reagent. Attempts to take advantage of this phenomenon with chiral 3-aminopyrrolidine (3-AP) lithium amides are described. The enantioselective protonation of a complex involving these amides and the lithium enolate of 2-methyltetralone by an achiral proton source gives products in which the ee does not exceed 40%. The same class of chiral amides is then applied to the asymmetric nucleophilic alkylation of aldehydes using alkyllithiums and phenyllithium. In this case, a mixed aggregate made up of the lithium amide and the alkyllithium, a structure that has been detailed previously in comparable situations, seems to be directly involved in the reaction. Thus, higher asymmetric inductions are obtained, affording the alkylation products in ee of up to 70%.