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Base-free enantioselective C(1)-ammonium enolate catalysis exploiting aryloxides: a synthetic and mechanistic study

Research output: Contribution to journalArticle

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  • Embargoed (until 12/09/20)

Abstract

An isothiourea‐catalyzed enantioselective Michael addition of aryl ester pronucleophiles to vinyl bis‐sulfones via C(1)‐ammonium enolate intermediates has been developed. This operationally simple method allows the base‐free functionalization of aryl esters to form α‐functionalized products containing two contiguous tertiary stereogenic centres in excellent yield and stereoselectivity (all ≥ 99:1 er). Key to the success of this methodology is the multifunctional role of the aryloxide, which operates as a leaving group, Brønsted base, Brønsted acid and Lewis base within the catalytic cycle. Comprehensive mechanistic studies, including variable time normalization analysis (VTNA) and isotopologue competition experiments, have been carried out. These studies have identified (i) orders of all reactants; (ii) a turnover‐limiting Michael addition step, (iii) product inhibition, (iv) the catalyst resting state and (v) catalyst deactivation through protonation.
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Details

Original languageEnglish
Pages (from-to)15111-15119
Number of pages9
JournalAngewandte Chemie International Edition
Volume58
Issue number42
Early online date12 Sep 2019
DOIs
Publication statusPublished - 14 Oct 2019

    Research areas

  • Enantioselective Michael addition, Inverse secondary kinetic isotope effect, Isothiourea catalysis, Mechanistic analysis, VTNA

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