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

The alkylation reactions of enolates derived from the highly diastereo selective conjugate additions of lithium (R)-N-benzyl-N-alpha-methylbe nzylamide (R)-1 to N,N-dimethyl crotonamide 2 and N,N-dimethyl cinnami de 3 have been investigated. The alkylations of enolates derived from 3 are shown to afford anti-alpha-alkyl-beta-amino carboxamides with ex cellent stereocontrol: the stereochemistry is assigned with the aid of a single crystal X-ray structure of (2R,3S,alpha R)-N,N-dimethyl -3-( N-benzyl-N-alpha-methylbenzylamino)propanamide (2R,3S,alpha R)-10. As a result of the difficulty encountered in hydrolysing these hindered b eta-amino amides such as 10, an alternative procedure is developed inv olving conjugate addition-alkylations with alpha,beta-unsaturated N-ac yloxazolidin-2-ones as substrates, giving selectively alkylated produc ts which are susceptible to reductive cleavage.