A C=O•••isothiouronium interaction dictates enantiodiscrimination in acylative kinetic resolution 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 resolution 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 journal › Article › peer-review

93 Citations (Scopus)

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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	19 Feb 2018
DOIs	https://doi.org/10.1002/anie.201712456
Publication status	Published - 12 Mar 2018

Keywords

Acylation
Kinetic resolution
Lewis bases
Organocatalysis
Tertiary alcohols

Access to Document

10.1002/anie.201712456

Revised Manuscript
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This work has been made available online in accordance with the publisher’s policies. This is the author created accepted version manuscript following peer review and as such may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1002/anie.201712456
Accepted author manuscript, 1.52 MB

RS Wolfson Merit Award: Developing Catalysis Research: New Reaction Discoveries and Practical Applications
Smith, A. D. (PI)
The Royal Society
1/01/15 → 31/12/19
Project: Fellowship
ERC Starting Grant EnolCat: Emulating nature: Reaction diversity and understanding through asymmetric catalysis
Smith, A. D. (PI)
European Commission
1/10/11 → 30/06/17
Project: Standard

Andrew David Smith
- ads10st-andrews.acuk
- School of Chemistry - Professor, Director of Research
- Biomedical Sciences Research Complex
- EaSTCHEM
Person: Academic

Isothiourea-mediated acylative kinetic resolution of heterocyclic and acyclic tertiary alcohols (thesis data)
Smith, S. (Creator) & Smith, A. D. (Supervisor), University of St Andrews, 6 Nov 2023
DOI: 10.17630/e1e170df-9006-4348-bc1e-1c57a3c032be, http://hdl.handle.net/10023/16470
Dataset: Thesis dataset

File
data underpinning "C=O•••Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolution of Tertiary Heterocyclic Alcohols"
Smith, A. D. (Creator), Greenhalgh, M. D. (Owner), Smith, S. (Owner) & Taylor, J. E. (Owner), University of St Andrews, 21 Feb 2018
DOI: 10.17630/e8b7bd1c-15d2-4ea3-9f34-02d87ad0435c
Dataset

File
A C=O•••isothiouronium interaction dictates enantiodiscrimination in acylative kinetic resolution of tertiary heterocyclic alcohols (dataset 2)
Greenhalgh, M. D. (Creator), Smith, S. (Creator), Walden, D. M. (Creator), Taylor, J. E. (Creator), Brice, Z. (Creator), Robinson, E. (Creator), Fallan, C. (Creator), Cordes, D. B. (Creator), Slawin, A. M. Z. (Creator), Richardson, H. C. (Creator), Grove, M. A. (Creator), Ha-Yeon Cheong, P. (Creator) & Smith, A. D. (Creator), Cambridge Crystallographic Data Centre, 2017
https://dx.doi.org/10.5517/ccdc.csd.cc1pq5k4 and one more link, https://dx.doi.org/10.5517/ccdc.csd.cc1pq5l5 (show fewer)
Dataset

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 resolution of tertiary heterocyclic alcohols. Angewandte Chemie International Edition, 57(12), 3200-3206. https://doi.org/10.1002/anie.201712456

@article{d1b5cdb2e2b0405bb952a05053a6d2c7,

title = "A C=O•••isothiouronium interaction dictates enantiodiscrimination in acylative kinetic resolution 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.}",

note = "The research leading to these results has received funding from the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013)/E.R.C. grant agreement n° 279850 and the EPSRC (EP/J500549/1). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. 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 the Bruce Graham and Johnson Fellowships of OSU. D.M.W. and P.H.-Y.C. acknowledge computing infrastructure in part provided by the NSF Phase-2 CCI, Center for Sustainable Materials Chemistry (CHE-1102637).",

year = "2018",

month = mar,

day = "12",

doi = "10.1002/anie.201712456",

language = "English",

volume = "57",

pages = "3200--3206",

journal = "Angewandte Chemie International Edition",

issn = "1433-7851",

publisher = "John Wiley & Sons, Ltd",

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}

Greenhalgh, MD, Smith, SM, Walden, DM, Taylor, JE, Brice, Z, Robinson, ERT, Fallan, C, Cordes, DB , Slawin, AMZ, Richardson, HC, Grove, MA, Cheong, PH-Y & Smith, AD 2018, 'A C=O•••isothiouronium interaction dictates enantiodiscrimination in acylative kinetic resolution of tertiary heterocyclic alcohols', Angewandte Chemie International Edition, vol. 57, no. 12, pp. 3200-3206. https://doi.org/10.1002/anie.201712456

TY - JOUR

T1 - A C=O•••isothiouronium interaction dictates enantiodiscrimination in acylative kinetic resolution 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.

N1 - The research leading to these results has received funding from the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013)/E.R.C. grant agreement n° 279850 and the EPSRC (EP/J500549/1). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. 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 the Bruce Graham and Johnson Fellowships of OSU. D.M.W. and P.H.-Y.C. acknowledge computing infrastructure in part provided by the NSF Phase-2 CCI, Center for Sustainable Materials Chemistry (CHE-1102637).

PY - 2018/3/12

Y1 - 2018/3/12

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

U2 - 10.1002/anie.201712456

DO - 10.1002/anie.201712456

M3 - Article

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 resolution of tertiary heterocyclic alcohols

Abstract

Keywords

Access to Document

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Projects

RS Wolfson Merit Award: Developing Catalysis Research: New Reaction Discoveries and Practical Applications

ERC Starting Grant EnolCat: Emulating nature: Reaction diversity and understanding through asymmetric catalysis

Profiles

Andrew David Smith

Datasets

Isothiourea-mediated acylative kinetic resolution of heterocyclic and acyclic tertiary alcohols (thesis data)

data underpinning "C=O•••Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolution of Tertiary Heterocyclic Alcohols"

A C=O•••isothiouronium interaction dictates enantiodiscrimination in acylative kinetic resolution of tertiary heterocyclic alcohols (dataset 2)

Cite this