Isothiourea-catalyzed acylative kinetic resolution of tertiary α-hydroxy esters

Shen Qu, Samuel Smith, Victor Laina-Martin, Rifahath Neyyappadath, Mark David Greenhalgh, Andrew David Smith

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13 Citations (Scopus)
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Abstract

A highly enantioselective isothiourea-catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically-congested alcohols, the use of a recently-developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure has also been translated to a continuous flow process using a polymer-supported variant of the catalyst.
Original languageEnglish
Pages (from-to)16572-16578
Number of pages8
JournalAngewandte Chemie International Edition
Volume59
Issue number38
Early online date16 Jul 2020
DOIs
Publication statusPublished - 14 Sept 2020

Keywords

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

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