Scope, limitations and mechanistic analysis of the HyperBTM-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols
Abstract
The full scope and limitations of the catalytic acylative kinetic resolution of a range of tertiary heterocyclic alcohols (78 examples, s up to >200) is reported under operationally-simple conditions, using low loadings of a commercially available Lewis basic isothiourea catalyst, HyperBTM (generally 1 mol %). The protocol is highly effective for the kinetic resolution of 3-substituted 3-hydroxyoxindole and α-substituted α-hydroxylactam derivatives bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. The full power of this methodology has been showcased through the synthesis of highly enantioenriched biologically-active target compounds in both enantiomeric forms. To provide further insight into the reaction mechanism, a detailed kinetic analysis of this Lewis base-catalyzed acylation of tertiary alcohols is reported using the variable time normalization analysis (VTNA) method.
Citation
Smith , S , Greenhalgh , M D , Feoktistova , T , Walden , D M , Taylor , J E , Cordes , D B , Slawin , A M Z , Cheong , P H-Y & Smith , A D 2022 , ' Scope, limitations and mechanistic analysis of the HyperBTM-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols ' , European Journal of Organic Chemistry , pp. 30-43 . https://doi.org/10.1002/ejoc.202101111
Publication
European Journal of Organic Chemistry
Status
Peer reviewed
ISSN
1434-193XType
Journal article
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. 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 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
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