A C=O⋅⋅⋅Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols

Mark D. Greenhalgh, Samuel M. Smith, Daniel M. Walden, James E. Taylor, Zamira Brice, Emily R.T. Robinson, Charlene Fallan, David B. Cordes, Alexandra M.Z. Slawin, H. Camille Richardson, Markas A. Grove, Paul Ha Yeon Cheong, Andrew D. Smith

Research output: Contribution to journalArticle

  • 4 Citations

Abstract

A combination of experimental and computational studies have identified a C=O⋅⋅⋅isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200). The reaction proceeds at low catalyst loadings (generally 1 mol %) with either isobutyric or acetic anhydride as the acylating agent under mild conditions.

LanguageEnglish
Pages3200-3206
Number of pages7
JournalAngewandte Chemie - International Edition
Volume57
Issue number12
Early online date12 Jan 2018
DOIs
StatusPublished - 12 Mar 2018

Fingerprint

Isothiuronium
Alcohols
Bearings (structural)
Kinetics
Methanol
Catalysts

Keywords

  • acylation
  • kinetic resolution
  • Lewis bases
  • organocatalysis
  • tertiary alcohols

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

A C=O⋅⋅⋅Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols. / Greenhalgh, Mark D.; Smith, Samuel M.; Walden, Daniel M.; Taylor, James E.; Brice, Zamira; Robinson, Emily R.T.; Fallan, Charlene; Cordes, David B.; Slawin, Alexandra M.Z.; Richardson, H. Camille; Grove, Markas A.; Cheong, Paul Ha Yeon; Smith, Andrew D.

In: Angewandte Chemie - International Edition, Vol. 57, No. 12, 12.03.2018, p. 3200-3206.

Research output: Contribution to journalArticle

Greenhalgh, MD, Smith, SM, Walden, DM, Taylor, JE, Brice, Z, Robinson, ERT, Fallan, C, Cordes, DB, Slawin, AMZ, Richardson, HC, Grove, MA, Cheong, PHY & Smith, AD 2018, 'A C=O⋅⋅⋅Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols' Angewandte Chemie - International Edition, vol. 57, no. 12, pp. 3200-3206. https://doi.org/10.1002/anie.201712456
Greenhalgh, Mark D. ; Smith, Samuel M. ; Walden, Daniel M. ; Taylor, James E. ; Brice, Zamira ; Robinson, Emily R.T. ; Fallan, Charlene ; Cordes, David B. ; Slawin, Alexandra M.Z. ; Richardson, H. Camille ; Grove, Markas A. ; Cheong, Paul Ha Yeon ; Smith, Andrew D. / A C=O⋅⋅⋅Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols. In: Angewandte Chemie - International Edition. 2018 ; Vol. 57, No. 12. pp. 3200-3206.
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