Lewis Base‐Catalysed Enantioselective Radical Conjugate Addition for the Synthesis of Enantioenriched Pyrrolidinones

• Published in: Angewandte Chemie Vol. 134; no. 26
• Main Authors: Hartley, Will C., Schiel, Florian, Ermini, Elena, Melchiorre, Paolo
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 27.06.2022
• Subjects: Ammonium; Asymmetry; Catalysis; Catalysts; Chemistry; Conjugates; Decarboxylation; Enantiomers; Enantioselectivity; Esters; Intermediates; Lewis base; Lewis Base Catalysis; Organocatalysis; Photochemistry; Photoredox catalysis; Radical Reactions; Radicals
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202204735

We report a catalytic asymmetric protocol for the preparation of chiral pyrrolidinones proceeding via a radical pathway. The chemistry exploits the combination of photoredox catalysis and Lewis base catalysis to realise the first example of asymmetric radical conjugate addition to α,β‐unsaturated anhydrides and esters. The reaction is initiated by photoredox activation of N‐arylglycines to generate, upon decarboxylation, α‐amino radicals. These radicals are then intercepted stereoselectively by α,β‐unsaturated acyl ammonium intermediates, whose formation is mastered by a chiral isothiourea organocatalyst. Cyclisation leads to catalyst turnover and formation of enantioenriched pyrrolidinones. The utility of the protocol was demonstrated with application to the synthesis of biologically‐active γ‐amino butyric acids. The combination of photoredox catalysis and Lewis base catalysis has been developed to realise the first example of asymmetric radical conjugate addition to α,β‐unsaturated anhydrides and esters. The chemistry, mastered by a chiral isothiourea organocatalyst, enables the synthesis of enantioenriched pyrrolidinones, with application to the synthesis of biologically‐active γ‐amino butyric acids.