title: Cinchona Alkaloid-Catalyzed Asymmetric Conjugate Additions: The Bifunctional Brønsted Acid-Hydrogen Bonding Model.
abstract: Wynberg's report from 1977 that natural cinchona alkaloids catalyze the asymmetric conjugate addition of aromatic thiols to cycloalkenones is a landmark discovery in hydrogen bonding organocatalysis. Wynberg proposed that this reaction proceeded via the formation of a thiolate-alkylammonium tight ion pair and activation of the enone electrophile by a hydrogen bond from the catalyst's hydroxyl group. This reaction model provided the mechanistic basis for understanding Wynberg's reaction and many other asymmetric transformations since. Our quantum mechanical calculations reveal a different model should be used to explain the results: the alkylammonium ion activates the enone by Brønsted acid catalysis, and the catalyst's hydroxyl group orients the thiolate nucleophile. The new model rationalizes the stereoselective outcome of Wynberg's reaction and provides a new, general model for asymmetric cinchona organocatalysis.
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095-1569, United States.|Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Grayson
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095-1569, United States.
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
mesh_terms: D002384:Catalysis; D002929:Cinchona / Q000737:chemistry*; D002930:Cinchona Alkaloids / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D015394:Molecular Structure; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds
chemical_list: D002930:Cinchona Alkaloids; D013438:Sulfhydryl Compounds