Dynamic Kinetic Asymmetric Transformations of β-Stereogenic α-Ketoesters by Direct Aldolization


  • The project described was supported by Award No. R01 GM084927 from the National Institute of General Medical Sciences. M.T.C. acknowledges the University of North Carolina at Chapel Hill Department of Chemistry for an Ernest L. Eliel Graduate Fellowship. X-ray crystallography was performed by Dr. Peter S. White.


Dynamic kinetic asymmetric transformations (DyKAT) of racemic β-bromo-α-keto esters by direct aldolization of nitromethane and acetone provide access to fully substituted α-glycolic acid derivatives bearing a β-stereocenter. The aldol adducts are obtained in excellent yield with high relative and absolute stereocontrol under mild reaction conditions. Mechanistic studies determined that the reactions proceed through a facile catalyst-mediated racemization of the β-bromo-α-keto esters under a DyKAT Type I manifold.