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

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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.

Original languageEnglish
Pages (from-to)3200-3206
Number of pages7
JournalAngewandte Chemie - International Edition
Volume57
Issue number12
Early online date12 Jan 2018
DOIs
Publication statusPublished - 12 Mar 2018

Keywords

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

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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    Greenhalgh, M. D., Smith, S. M., Walden, D. M., Taylor, J. E., Brice, Z., Robinson, E. R. T., Fallan, C., Cordes, D. B., Slawin, A. M. Z., Richardson, H. C., Grove, M. A., Cheong, P. H. Y., & Smith, A. D. (2018). A C=O⋅⋅⋅Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols. Angewandte Chemie - International Edition, 57(12), 3200-3206. https://doi.org/10.1002/anie.201712456