Cinchona alkaloid-catalyzed Mannich reactions

ORGN 31

Sha Lou, slou@bu.edu, Amal Ting, Brandon M. Taoka, and Scott E. Schaus, seschaus@bu.edu. Department of Chemistry and Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, Life Science and Engineering Building, 24 Cummington Street, Boston, MA 02215
Cinchona Alkaloids catalyze the enantioselective Mannich reaction of stabilized anions with acyl imines. The reaction conditions have been developed to employ acyl imines and acyl imine precursors, α-amido sulphones. The reaction requires 10 mol% of cinchona alkaloid catalyst. We have obtained the reaction products in good yields, high enantioselectivities, and in diastereoselectivities that range from 1:1 to >95:5. The cinchonine-catalyzed reactions provide practical access to highly functionalized building blocks. The reaction of β-keto esters with acyl imines affords intermediates for synthesis of chiral dihydropyrimidones, a class of compounds pharmacologically rich in diverse biological activity.