Diphenylprolinol silyl ether catalyzed asymmetric Michael reaction of nitroalkanes and β,β-disubstituted α,β-unsaturated aldehydes for the construction of all-carbon quaternary stereogenic centers

Yujiro Hayashi, Yuya Kawamoto, Masaki Honda, Daichi Okamura, Shigenobu Umemiya, Yuka Noguchi, Takasuke Mukaiyama, Itaru Sato

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

The asymmetric Michael reaction of nitroalkanes and β,β-disubstituted α,β-unsaturated aldehydes was catalyzed by diphenylprolinol silyl ether to afford 1,4-addition products with an all-carbon quaternary stereogenic center with excellent enantioselectivity. The reaction is general for β-substituents such as β-aryl and β-alkyl groups, and both nitromethane and nitroethane can be employed. The addition of nitroethane is considered a synthetic equivalent of the asymmetric Michael reaction of ethyl and acetyl substituents by means of radical denitration and Nef reaction, respectively. The short asymmetric synthesis of (S)-ethosuximide with a quaternary carbon center was accomplished by using the present asymmetric Michael reaction as the key step. The reaction mechanism that involves the E/Z isomerization of α,β-unsaturated aldehydes, the retro-Michael reaction, and the different reactivity between nitromethane and nitroethane is discussed.

Original languageEnglish
Pages (from-to)12072-12082
Number of pages11
JournalChemistry - A European Journal
Volume20
Issue number38
DOIs
Publication statusPublished - 2014 Sep 15

Keywords

  • Michael addition
  • asymmetric synthesis
  • enantioselectivity
  • isomerization
  • organocatalysis

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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