Year: 2025
Type: article
Abstract: In this study, we report on the use of mechanochemistry for the synthesis of trifluoromethylated isoindolinones via a cascade radical sequence involving intermolecular addition/cyclization reactions of ynamides. This minimum solvent approach, involving liquid‐assisted grinding, provides the products in good yields with complete E stereoselectivity, contrasting with the E/Z mixtures obtained under previously reported photoredox conditions. Mechanistic investigations revealed two complementary activation pathways: mechanical activation alone can trigger the radical cascade, while the presence of piezoelectric materials (BaTiO 3 ) significantly accelerates product formation. Furthermore, we identified an unexpected role of Celite® as an abrasive agent that promotes metal leaching and enables alternative activation pathways. This methodology showcases mechanochemistry as a valuable alternative to photoredox catalysis for stereoselective radical transformations, with distinct mechanistic advantages that can be strategically exploited.
Source: Helvetica Chimica Acta
Authors: Amal Lakhal, Louis Fensterbank, Cyril Ollivier
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W4413383058