Mechanism and Origin of Stereoselectivity in Chiral Phosphoric Acid-Catalyzed Aldol-Type Reactions of Azlactones with Vinyl Ethers

Kyohei Kanomata, Yuki Nagasawa, Yukihiro Shibata, Masahiro Yamanaka, Fuyuki Egawa, Jun Kikuchi, Masahiro Terada

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The precise mechanism of the chiral phosphoric acid-catalyzed aldol-type reaction of azlactones with vinyl ethers was investigated. DFT calculations suggested that the reaction proceeds through a Conia-ene-type transition state consisting of the vinyl ether and the enol tautomer of the azlactone, in which the catalyst protonates the nitrogen atom of the azlactone to promote enol tautomerization. In addition, the phosphoryl oxygen of the catalyst interacts with the vinyl proton of the vinyl ether. The favorable transition structure features dicoordinating hydrogen bonds. However, these hydrogen bonds are not involved in the bond recombination sequence and hence the catalyst functions as a template for binding substrates. From the results of theoretical studies and experimental supports, the high enantioselectivity is induced by the steric repulsion between the azlactone substituent and the binaphthyl backbone of the catalyst under the catalyst template effect.

Original languageEnglish
Pages (from-to)3364-3372
Number of pages9
JournalChemistry - A European Journal
Volume26
Issue number15
DOIs
Publication statusPublished - 2020 Mar 12

Keywords

  • asymmetric synthesis
  • density functional calculations
  • enantioselectivity
  • organocatalysis
  • reaction mechanisms

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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