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

An investigation into the asymmetric induction accompanying alkylations of enolates derived from the highly diastereoselective conjugate addition of lithium (R)-N-benzyl-N-alpha-methylbenzylamide (R)-1 to crotonate and cinnamate esters has been performed. The access to different enolate geometries afforded by the conjugate addition process and subsequent enolate regeneration by deprotonation of the beta-amino ester conjugate 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 considerably more selective. Several factors which play a major role in determining the alkylation selectivity are identified. including the cooperative influence of the alpha-methylbenzylamino stereocentre. Since debenzylation and hydrolysis of the alkylated products was straightforward, this methodology provides a direct route to anti-alpha-alkyl-beta-amino acids in homochiral form.