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

University of St Andrews
Oregon State University

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

111 Citations (SciVal)

214 Downloads (Pure)

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

Funding

[*] Dr. M. D. Greenhalgh, S. M. Smith, Dr. J. E. Taylor, Z. Brice, E. R. T. Robinson, Dr. C. Fallan, Dr. D. B. Cordes, Prof. A. M. Z. Slawin, Prof. A. D. Smith EaStCHEM, School of Chemistry University of St Andrews North Haugh, St Andrews, Fife, KY16 9ST (UK) E-mail: [email protected] D. M. Walden, H. C. Richardson, M. A. Grove, Prof. P. H.-Y. Cheong Department of Chemistry, Oregon State University 153 Gilbert Hall, Corvallis, OR 97331 (USA) E-mail: [email protected] Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.201712456. The research leading to these results has received funding from the ERC under the European Union≫s Seventh Frame-work Programme (FP7/2007–2013)/E.R.C. grant agreement 279850 and the EPSRC (EP/J500549/1). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. We thank the EPSRC UK National Mass Spectrometry Facility at Swansea University. P.H.-Y.C. is the Bert and Emelyn Christensen Professor and gratefully acknowledges financial support from the Stone Family of OSU. Financial support from the National Science Foundation (NSF; CHE-1352663) is acknowledged. D.M.W. acknowledges Bruce Graham, Johnson, and N.L. Tartar fellowships of OSU. D.M.W. and P.H.-Y.C. acknowledge the use of computing infrastructure in part provided by the NSF Phase-2 CCI, Center for Sustainable Materials Chemistry (CHE-1102637).

Keywords

acylation
kinetic resolution
Lewis bases
organocatalysis
tertiary alcohols

ASJC Scopus subject areas

Catalysis
General Chemistry

Access to Document

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

@article{39c4043be374412a9d9d26dea701e534,

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

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",

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

year = "2018",

month = mar,

day = "7",

doi = "10.1002/anie.201712456",

language = "English",

volume = "57",

pages = "3200--3206",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "John Wiley and Sons Inc.",

number = "12",

}

TY - JOUR

T1 - A C=O⋅⋅⋅Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols

AU - Greenhalgh, Mark D.

AU - Smith, Samuel M.

AU - Walden, Daniel M.

AU - Taylor, James E.

AU - Brice, Zamira

AU - Robinson, Emily R.T.

AU - Fallan, Charlene

AU - Cordes, David B.

AU - Slawin, Alexandra M.Z.

AU - Richardson, H. Camille

AU - Grove, Markas A.

AU - Cheong, Paul Ha Yeon

AU - Smith, Andrew D.

PY - 2018/3/7

Y1 - 2018/3/7

N2 - 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.

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.

KW - acylation

KW - kinetic resolution

KW - Lewis bases

KW - organocatalysis

KW - tertiary alcohols

UR - https://www.scopus.com/pages/publications/85042110491

U2 - 10.1002/anie.201712456

DO - 10.1002/anie.201712456

M3 - Article

AN - SCOPUS:85042110491

SN - 1433-7851

VL - 57

SP - 3200

EP - 3206

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 12

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

James Taylor

Cite this

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Profiles

James Taylor

Cite this