Cinchona Urea-Catalyzed Asymmetric Sulfa-Michael Reactions: The Brønsted Acid-Hydrogen Bonding Model

Matthew N. Grayson, K. N. Houk

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The cinchona alkaloid-derived urea-catalyzed asymmetric conjugate addition of aromatic thiols to cycloalkenones was studied using density functional theory (DFT). Deprotonation of the thiol gives a protonated amine that activates the electrophile by Brønsted acid catalysis, while the urea group binds the nucleophilic thiolate by hydrogen bonding. These results demonstrate the generality of the Brønsted acid-hydrogen bonding transition state (TS) model for cinchona alkaloid catalysis that we recently showed to be favored over Wynberg's widely accepted ion pair-hydrogen bonding model and represent the first detailed mechanistic study of a cinchona urea-catalyzed reaction. The conformation of the catalyst methoxy group has a strong effect on the TS, an effect overlooked in previous mechanistic studies of reactions catalyzed by cinchona alkaloids.

Original languageEnglish
Pages (from-to)9041-9044
Number of pages4
JournalJournal of the American Chemical Society
Volume138
Issue number29
Early online date9 Jul 2016
DOIs
Publication statusPublished - 27 Jul 2016

ASJC Scopus subject areas

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

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