Enantio- and diastereoselective michael addition reactions of unmodified aldehydes and ketones with nitroolefins catalyzed by a pyrrolidine sulfonamide

Jian Wang, Hao Li, Bihshow Lou, Liansuo Zu, Hua Guo, Wei Wang

Research output: Contribution to journalArticlepeer-review

221 Scopus citations

Abstract

Chiral (S)-pyrrolidine trifluoromethanesulfonamide has been shown to serve as an effective catalyst for direct Michael addition reactions of aldehydes and ketones with nitroolefins. A wide range of aldehydes and ketones as Michael donors and nitroolefins as acceptors participate in the process, which proceeds with high levels of enantioselectivity (up to 99% ee) and diastereoselectivity (up to 50:1 d.r.). The methodology has been employed successfully in an efficient synthesis of the potent H., agonist Sen 50917. In addition, a practical three-step procedure for the preparation of (S)-pyrrolidine trifluorometh-anesulfonamide has been developed. The high levels of stereochemical control attending Michael addition reactions catalyzed by this pyrrolidine sulfonamide, have been investigated by using ab initio and density functional methods. Transition state structures for the rate-limiting C-C bond-forming step, corresponding to re- and si-face addition to the reactive conformation of the key enamine intermediates have been calculated. Analysis of these structures indicates that hydrogen bonding plays an important role in catalysis and that the energy barrier for si-face attack in reactions of aldehydes to form 2R,3S products is lower than that for the re-face attack leading to 2S,3R products. In contrast, the energy barrier for re-face addition is lower than that for si-face addition in reactions of ketones. The computational results, which are in good agreement with the experimental observations, are discussed in the context of the stereo-chemical course of these Michael addition reactions.

Original languageEnglish (US)
Pages (from-to)4321-4332
Number of pages12
JournalChemistry - A European Journal
Volume12
Issue number16
DOIs
StatePublished - May 24 2006
Externally publishedYes

Keywords

  • Asymmetric catalysis
  • Michael addition
  • Nitroolefin
  • Organocatalysis
  • Pyrrolidine sulfonamide

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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