Catalytic Generation of Ammonium Enolates and Related Tertiary Amine-Derived Intermediates: Applications, Mechanism, and Stereochemical Models (n → π*)

Ammonium enolates are covalently bound, neutral zwitterionic enolates prepared by the reaction of tertiary amines and various electrophilic substrates including acid halides, α-halo carbonyls, and α,β-unsaturated carbonyls. The reaction mechanism was proposed to involve formation of chiral ammonium enolate, which is responsible for the chiral induction upon a-protonation. In 1999, Fu and coworkers investigated the enantioselective addition of alcohols to ketenes using their previously developed class of chiral Lewis bases, namely, enantioenriched 4-dimethylamino pyridines (DMAP) and pyrrolo ferrocenes. Based on the working mechanistic hypothesis that the reaction follows, a nucleophilic addition to ketene followed by a diastereoselective protonation of the intermediate ammonium enolate, several proton sources were studied. The study of ketene aminolysis raised the possibility of a proton transfer to generate a catalytically active Bronsted acid intermediate in the enantioselective alcoholysis of ketenes. Exquisite control of both absolute and relative stereochemistry of stereogenic carbon centers is crucial in modern polypropionate synthesis.