Asymmetric Mannich reaction of dicarbonyl compounds with alpha-amido sulfones catalyzed by cinchona alkaloids and synthesis of chiral dihydropyrimidones.
The highly enantioselective cinchona alkaloid-catalyzed Mannich reaction of dicarbonyl compounds with alpha-amido sulfones as acyl imine precursors is described. The reaction requires 10 mol % of the cinchona alkaloid catalyst, which serves as a general base to generate acyl imines in situ, and aqueous Na2CO3 to maintain the concentration of free alkaloid catalyst. The reaction products are obtained in good yields and 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 which have been employed in the synthesis of chiral dihydropyrimidones, a class of compounds rich in diverse biological activity. Dihydropyrimidone modifications include a highly diastereoselective hydrogenation of the enamide moiety, using an H-Cube flow hydrogenator and a Rh(II)-mediated 1,3-dipolar cycloaddition to afford highly functionalized complex heterocycles.
Lou
Sha
S
Department of Chemistry, Center for Chemical Methodology and Library Development, Life Science and Engineering Building, Boston University, 24 Cummington Street, Boston, Massachusetts 02215, USA.
Dai
Peng
P
Schaus
Scott E
SE
D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D004952:Esters / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis; D013237:Stereoisomerism; D013450:Sulfones / Q000737:chemistry*
D002930:Cinchona Alkaloids; D004952:Esters; D007659:Ketones; D011744:Pyrimidinones; D054852:Small Molecule Libraries; D013450:Sulfones