The importance of 1,5-oxygen-chalcogen interactions in enantioselective isochalcogenourea catalysis

Claire Young, Alex Elmi, Dominic Pascoe, Rylie Morris, Calum McLaughlin, Andrew Woods, Aileen Frost, Alix de la Houpliere, Kenneth Ling, Terry K Smith, Alexandra M. Z. Slawin, Patrick Willoughby, Scott Cockroft, Andrew Smith

Research output: Contribution to journalArticlepeer-review

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 via intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N ‐acylated intermediates.
Original languageEnglish
JournalAngewandte Chemie International Edition
Early online date19 Dec 2019
DOIs
Publication statusE-pub ahead of print - 19 Dec 2019

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