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

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Date

12/03/2018

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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

Citation

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 , vol. 57 , no. 12 , pp. 3200-3206 . https://doi.org/10.1002/anie.201712456

Publication

Angewandte Chemie International Edition

Status

Peer reviewed

DOI

https://doi.org/10.1002/anie.201712456

ISSN

1433-7851

Type

Journal article

Rights

© 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

Description

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).

Collections

University of St Andrews Research

URI

http://hdl.handle.net/10023/17091