The importance of 1,5-oxygen···chalcogen interactions in enantioselective isochalcogenourea catalysis
Abstract
The importance of 1,5-O···chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch = O, S, Se) is investigated. Conformational analyses of N-acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5-O···Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram-scale synthesis of the most active selenium analogue was developed using a previously unreported seleno-Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density Functional Theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N-acylated intermediates.
Citation
Young , C M , Elmi , A , Pascoe , D J , Morris , R K , McLaughlin , C , Woods , A , Frost , A , De La Houpliere , A , Ling , K B , Smith , T K , Slawin , A M Z , Willoughby , P H , Cockroft , S L & Smith , A D 2020 , ' The importance of 1,5-oxygen···chalcogen interactions in enantioselective isochalcogenourea catalysis ' , Angewandte Chemie International Edition , vol. 59 , no. 9 , pp. 3705-3710 . https://doi.org/10.1002/anie.201914421
Publication
Angewandte Chemie International Edition
Status
Peer reviewed
ISSN
1433-7851Type
Journal article
Description
Syngenta (Case Award to DJP) and a Philip Leverhulme Prize for funding (SLC, AE). RKM and PHW are grateful to the American Chemical Society Petroleum Research Fund and National Science Foundation (NSF-MRI: CHE-1429616).Collections
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