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The Importance of 1,5‐Oxygen⋅⋅⋅Chalcogen Interactions in Enantioselective Isochalcogenourea Catalysis
Author(s) -
Young Claire M.,
Elmi Alex,
Pascoe Dominic J.,
Morris Rylie K.,
McLaughlin Calum,
Woods Andrew M.,
Frost Aileen B.,
Houpliere Alix,
Ling Kenneth B.,
Smith Terry K.,
Slawin Alexandra M. Z.,
Willoughby Patrick H.,
Cockroft Scott L.,
Smith Andrew D.
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201914421
Subject(s) - natural bond orbital , chemistry , enantioselective synthesis , chalcogen , intramolecular force , catalysis , nitronate , reactivity (psychology) , computational chemistry , organocatalysis , density functional theory , stereochemistry , organic chemistry , medicine , nitro , alkyl , alternative medicine , pathology
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.