Mukaiyama-Michael reactions with trans-2,5-diarylpyrrolidine catalysts: Enantioselectivity arises from attractive noncovalent interactions, not from steric hindrance

Eeva K. Kemppainen, Gokarneswar Sahoo, Antti Piisola, Andrea Hamza, Bianka Kõtai, Imre Pápai, Petri M. Pihko

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The scope of the enantioselective Mukaiyama-Michael reactions catalyzed by trans-2,5-diphenylpyrrolidine has been expanded to include both α- and β-substituted enals. However, the rationalization of the observed enantioselectivity is far from obvious since the catalyst is not very sterically hindered. DFT calculations were carried out to rationalize the observed stereoselectivities. Transition states of the C-C bond formation between iminium intermediates and silyloxyfurans were located and their relative energies were used to estimate the stereoselectivity data. We find excellent agreement between the predicted and observed stereoselectivities. The analysis of intermolecular forces reveals that the enantioselectivity is mostly due to stabilizing noncovalent interactions between the reacting partners, not due to steric hindrance. The role of attractive noncovalent interactions in enantioselective catalysis may be underappreciated. Embraced enantioselectivity: Mukaiyama-Michael reactions catalyzed by trans-2,5-diphenylpyrrolidine catalyst are highly enantioselective, but why? The answer appears to lie in the attractive, not repulsive, noncovalent interactions in the transition states leading to the major product(s) (see scheme; TIPS=triisopropylsilyl).

Original languageEnglish
Pages (from-to)5983-5993
Number of pages11
JournalChemistry - A European Journal
Volume20
Issue number20
DOIs
Publication statusPublished - May 12 2014

Keywords

  • DFT calculations
  • enantioselectivity
  • noncovalent interactions
  • organocatalysis
  • transition states

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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