I. Enantioselective Acylation of Silyl Ketene Acetals through Fluoride Anion-Binding Catalysis II. Development of a Practical Method for the Synthesis of Highly Enantioenriched trans-1,2-Amino Alcohols

A highly enantioselective acylation of silyl ketene acetals with acyl fluorides was developed to generate useful alpha,alpha-disubstituted butyrolactone products in high yield and excellent enantioselectivities. This transformation is promoted by an arylpyrrolidino thiourea catalyst and 4-pyrrolidinopyridine and represents the first example of enantioselective thiourea anion-binding catalysis with fluoride. Mechanistic investigations revealed both catalysts to be necessary for reaction to occur, suggesting the thiourea aids in the generation of the key N-acylpyridinium/fluoride ion pair. The outstanding hydrogen-bond-accepting ability of fluoride is likely important in this regard. In addition, a strong dependence on both the N-acylpyridinium counteranion and the substituents on the silicon group of the silyl ketene acetal were observed, highlighting the importance of the silicon-fluoride interaction.