ASYMMETRIC-SYNTHESIS OF ANTI-ALPHA-ALKYL-BETA-AMINO ACIDS

An investigation into the asymmetric induction accompanying alkylation s of enolates derived from the highly diastereoselective conjugate add ition of lithium (R)-N-benzyl-N-alpha-methylbenzylamide (R)-1 to croto nate and cinnamate esters has been performed. The access to different enolate geometries afforded by the conjugate addition process and subs equent enolate regeneration by deprotonation of the beta-amino ester c onjugate adducts enabled two disparate sets of selectivity data to be compiled. Although both approaches furnished predominantly anti-alpha- alkyl-beta-amino esters. the two-step procedure proved to be considera bly more selective. Several factors which play a major role in determi ning the alkylation selectivity are identified. including the cooperat ive influence of the alpha-methylbenzylamino stereocentre. Since deben zylation and hydrolysis of the alkylated products was straightforward, this methodology provides a direct route to anti-alpha-alkyl-beta-ami no acids in homochiral form.