Development of chiral bisphosphoric acid/boronic acid co-catalyst system for enantioselective SN2’ reaction

Satavisha Kayal, Jun Kikuchi, Naoya Shinagawa, Shigenobu Umemiya, Masahiro Terada

Research output: Contribution to journalArticlepeer-review

Abstract

An enantioselective intramolecular SN2’ reaction of geometrically defined allylic substrates was developed by introducing a co-catalyst system composed of chiral bisphosphoric acid and phenylboronic acid. In the enantioselective nucleophilic substitution reaction using chiral phosphoric acids and derivatives (CPAs) as the catalyst, the formation of the corresponding CPA ester, which is afforded through the SN2 reaction of the substrate with the nucleophilic phosphate anion generated during the activation of a leaving group, has been a serious problem because of the catalyst deactivation. The developed co-catalyst system surmounted this fundamental problem by efficiently suppressing the catalyst deactivation process to afford enantioenriched vinyl epoxides in good yields with moderate to high enantioselectivities. Mechanistic elucidation of the present enantioselective intramolecular SN2’ reaction using the co-catalyst system revealed that the leaving group is involved in the enantio-determining transition states, and the anti-SN2’ pathway is considered to be the rational mechanism of the present allylic substitution reaction. In addition, the stereospecific Meinwald rearrangement of the thus-formed enantioenriched vinyl epoxide was aided by an equimolar amount of a Lewis acid, affording the corresponding all-carbon quaternary α-vinyl cyclohexanone without marked loss of enantiomeric purity.

Original languageEnglish
Article number132412
JournalTetrahedron
Volume98
DOIs
Publication statusPublished - 2021 Oct 8

Keywords

  • Chiral Brønsted acid
  • Organocatalysis
  • Quaternary stereogenic center
  • S2’ reaction
  • Vinyl epoxides

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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