Isothiourea-catalyzed acylative kinetic resolution of tertiary α-hydroxy esters
MetadataShow full item record
A highly enantioselective isothiourea-catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically-congested alcohols, the use of a recently-developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure has also been translated to a continuous flow process using a polymer-supported variant of the catalyst.
Qu , S , Smith , S , Laina-Martin , V , Neyyappadath , R , Greenhalgh , M D & Smith , A D 2020 , ' Isothiourea-catalyzed acylative kinetic resolution of tertiary α-hydroxy esters ' , Angewandte Chemie International Edition , vol. 59 , no. 38 , pp. 16572-16578 . https://doi.org/10.1002/anie.202004354
Angewandte Chemie International Edition
Copyright © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
DescriptionFunding: ERC under the European Union's Seventh Framework Programme (FP7/2007–2013)/E.R.C. grant agreement no. 279850. The Chinese Scholarship Scheme and University of St Andrews are thanked for a CSC Scholarship (S.Q.). Universidad Autónoma de Madrid is thanked for a predoctoral fellowship (V.L.-M.). We thank the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1) for funding (R.M.N.). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.