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

Claire Mary Young, Alex Elmi, Dominic J. Pascoe, Rylie K. Morris, Calum McLaughlin, Andrew Woods, Aileen Frost, Alix De La Houpliere, Kenneth B. Ling, Terry K Smith, Alexandra Martha Zoya Slawin, Patrick H. Willoughby, Scott L. Cockroft, Andrew David Smith

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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.
Original languageEnglish
Pages (from-to)3705-3710
JournalAngewandte Chemie International Edition
Volume59
Issue number9
Early online date3 Feb 2020
DOIs
Publication statusPublished - 17 Feb 2020

Keywords

  • Organocatalysis
  • Chalcogen bonding
  • Isothioureas
  • Isoselenoureas
  • 1,5-O···Ch
  • Asymmetric catalysis

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