Asymmetric alkylation of chiral N,N-disubstituted amides

Abstract

Chiral N,N-disubstituted amides may be readily synthesized by reacting an anhydride with l- or d-ephedrine. The alkylation of the carbanions derived from these amides affords α-substituted chiral ketones and acids after cleavage. A study of the reaction characteristics indicates that the nature of the counter ion (Li or Mg) is the critical factor in the asymmetric synthesis. In this way, (S)-(+)-4-methyl-3-heptanone, an alarm pheromone of "Atta Texana", was synthesized in 81% enantiomeric excess.