Enantioselective Alcoholysis of meso‐Glutaric Anhydrides Catalyzed by Cinchona‐Based Sulfonamide Catalysts

Abstract

AbstractThe bifunctional Cinchona‐based sulfonamide catalysts showed the highest levels of enantioselectivity reported to date in the alcoholytic desymmetrization of meso‐glutaric anhydrides. Density functional theory (DFT) computational studies provide detailed insight into the observed sense of enantioselectivity. Moreover, detailed experimental studies and single crystal X‐ray analysis confirmed that these bifunctional organocatalysts 3 do not form H‐bonded self‐aggregates in both solution and solid state. The synthetic utility of this methodology was also demonstrated in the synthesis of pharmaceutically important γ‐amino acids, such as (S)‐pregabalin. Of the many asymmetric syntheses of enantiomerically pure (S)‐pregabalin reported to date, our synthesis requires the least number of and the simplest steps.