Highly Stereoselective Asymmetric Aldol Routes to tert-Butyl-2-(3,5-difluorophenyl)-1-oxiran-2-yl)ethyl)carbamates: Building Blocks for Novel Protease Inhibitors

Enantioselective syntheses of tert-butyl ((S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate and ((S)-2-(3,5-difluorophenyl)-1-((R)-oxiran-2-yl)ethyl)carbamate are described. We utilized asymmetric syn- and anti-aldol reactions to set both stereogenic centers. We investigated ester-derived Ti-enolate aldol reactions as well as Evans' diastereoselective syn-aldol reaction for these syntheses. We have converted optically active ((S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate to a potent β-secretase inhibitor.