PROTONATION-ASSISTED CONJUGATE ADDITION OF AXIALLY CHIRAL ENOLATES: ASYMMETRIC SYNTHESIS OF β-LACTAMS WITH CONTIGUOUS TETRASUBSTITUTED STEREOCENTERS FROM α-AMINO ACIDS VIA MEMORY OF CHIRALITY

A method for asymmetric synthesis of highly strained beta-lactams with contiguous two tetrasubstituted stereocenters from readily available cc -amino acids has been developed via MOC strategy. In situ protonation of the labile alpha-lactam enolate intermediates formed through 4-exo-trig cyclization of the axially chiral enolates generated from alpha-amino acid derivatives seems to be the key to successfully produce highly strained P-lactams. A salient feature of this transformation is that a proton source does not quench axially chiral enolate C, but accelerate the overall reaction by protonation of the intermediary P-lactam enolate D.