Aminomethylation of enals through carbene and acid cooperative catalysis: concise access to β(2)-amino acids.

A convergent, organocatalytic asymmetric aminomethylation of alpha,beta -unsaturated aldehydes by N-heterocyclic carbene (NHC) and (in situ generated) Bronsted acid cooperative catalysis is disclosed. The catalytically generated conjugated acid from the base plays dual roles in promoting the formation of azolium enolate intermediate, formaldehydederived iminium ion (as an electrophilic reactant), and methanol (as a nucleophilic reactant). This redox-neutral strategy is suitable for the scalable synthesis of enantiomerically enriched beta(2)-amino acids bearing various substituents.