Scope, limitations and mechanistic analysis of the HyperBTM-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols

Sam Smith, Mark Greenhalgh, Taisiia Feoktistova, Daniel Walden, James Taylor, David Cordes, Alexandra Slawin, Paul Ha-Yeon Cheong, Andrew Smith

Research output: Contribution to journalArticlepeer-review

2 Citations (SciVal)
1 Downloads (Pure)

Abstract

The full scope and limitations of the catalytic acylative kinetic resolution of a range of tertiary heterocyclic alcohols (78 examples, s up to >200) is reported under operationally-simple conditions, using low loadings of a commercially available Lewis basic isothiourea catalyst, HyperBTM (generally 1 mol %). The protocol is highly effective for the kinetic resolution of 3-substituted 3-hydroxyoxindole and α-substituted α-hydroxylactam derivatives bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. The full power of this methodology has been showcased through the synthesis of highly enantioenriched biologically-active target compounds in both enantiomeric forms. To provide further insight into the reaction mechanism, a detailed kinetic analysis of this Lewis base-catalyzed acylation of tertiary alcohols is reported using the variable time normalization analysis (VTNA) method.

Original languageEnglish
Article numbere202101111
JournalEuropean Journal of Organic Chemistry
Volume2022
Issue number1
Early online date11 Nov 2021
DOIs
Publication statusPublished - 11 Jan 2022

Keywords

  • Acyl transfer
  • Enantioselectivity
  • Kinetic resolution
  • Organocatalysis
  • Tertiary alcohol

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Scope, limitations and mechanistic analysis of the HyperBTM-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols'. Together they form a unique fingerprint.

Cite this