A theoretical and experimental study of the effects of silyl substituents in enantioselective reactions catalyzed by diphenylprolinol silyl ether

Yujiro Hayashi, Daichi Okamura, Tatsuya Yamazaki, Yasuto Ameda, Hiroaki Gotoh, Seiji Tsuzuki, Tadafumi Uchimaru, Dieter Seebach

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The effect of silyl substituents in diphenylprolinol silyl ether catalysts was investigated. Mechanistically, reactions catalyzed by diphenylprolinol silyl ether can be categorized into three types: two that involve an iminium ion intermediate, such as for the Michael-type reaction (type A) and the cycloaddition reaction (type B), and one that proceeds via an enamine intermediate (type C). In the Michael-type reaction via iminium ions (type A), excellent enantioselectivity is realized when the catalyst with a bulky silyl moiety is employed, in which efficient shielding of a diastereotopic face of the iminium ion is directed by the bulky silyl moiety. In the cycloaddition reaction of iminium ions (type B) and reactions via enamines (type C), excellent enantioselectivity is obtained even when the silyl group is less bulky and, in this case, too much bulk reduces the reaction rate. In other cases, the yield increases when diphenylprolinol silyl ethers with bulky substituents are employed, presumably by suppressing side reactions between the nucleophilic catalyst and the reagent. The conformational behaviors of the iminium and enamine species have been determined by theoretical calculations. These data explain the effect of the bulkiness of the silyl substituent on the enantioselectivity and reactivity of the catalysts.

Original languageEnglish
Pages (from-to)17077-17088
Number of pages12
JournalChemistry - A European Journal
Volume20
Issue number51
DOIs
Publication statusPublished - 2014 Dec 15

Keywords

  • Asymmetric synthesis
  • Density functional calculations
  • Organocatalysis
  • Reaction mechanisms
  • Substituent effects

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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