Cinchona Alkaloid-Catalyzed Asymmetric Conjugate Additions: The Bifunctional Brønsted Acid-Hydrogen Bonding Model

Matthew N. Grayson, K. N. Houk

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Wynbergs 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 catalysts hydroxyl group. This reaction model provided the mechanistic basis for understanding Wynbergs 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 catalysts hydroxyl group orients the thiolate nucleophile. The new model rationalizes the stereoselective outcome of Wynbergs reaction and provides a new, general model for asymmetric cinchona organocatalysis.

Original languageEnglish
Pages (from-to)1170-1173
Number of pages4
JournalJournal of the American Chemical Society
Volume138
Issue number4
Early online date19 Jan 2016
DOIs
Publication statusPublished - 3 Feb 2016

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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