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

doi:10.1002/anie.201712456

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

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

55 Citations (SciVal)

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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 language	English
Pages (from-to)	3200-3206
Number of pages	7
Journal	Angewandte Chemie - International Edition
Volume	57
Issue number	12
Early online date	12 Jan 2018
DOIs	https://doi.org/10.1002/anie.201712456
Publication status	Published - 7 Mar 2018

Keywords

acylation
kinetic resolution
Lewis bases
organocatalysis
tertiary alcohols

ASJC Scopus subject areas

Catalysis
Chemistry(all)

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10.1002/anie.201712456

Manuscript 16.pdf
This is the peer-reviewed version of the following article: 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.which has been published in final form at https://doi.org/10.1002/anie.201712456. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Accepted author manuscript, 1.52 MB

Cite this

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

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

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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.",

keywords = "acylation, kinetic resolution, Lewis bases, organocatalysis, tertiary alcohols",

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AB - 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.

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

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James Taylor

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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James Taylor

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