Protonation-Assisted Conjugate Addition of Axially Chiral Enolates: Asymmetric Synthesis of Multisubstituted β-Lactams from α-Amino Acids

beta-Lactams with contiguous tetra- and trisubstituted carbon centers were prepared in a highly enantioselective manner through 4-exo-trig cyclization of axially chiral enolates generated from readily available a-amino acids. Use of a weak base (metal carbonate) in a protic solvent (EtOH) is the key to the smooth production of beta-lactams. Use of the weak base is expected to generate the axially chiral enolates in a very low concentration, which undergo intramolecular conjugate addition without suffering intermolecular side reactions. Highly strained beta-lactam enolates thus formed through reversible intramolecular conjugate addition (4-exo-trig cyclization) of axially chiral enolates undergo prompt protonation by EtOH in the reaction media (not during the work-up procedure) to give beta-lactams in up to 97% ee.