Energy Transfer Catalysis Enabled 2,2,2-Trifluoroethoxy-Amination of Olefins

Abstract

A thioxanthone-catalyzed 2,2,2-trifluoroethoxyamination of olefins is developed via the formation of the corresponding alkoxy and iminyl radicals using unprecedented, easily prepared, and bench-stable oxime ethers as bifunctional reagents. To bypass possible side reactions (1,2-Hydrogen Atom Transfer (HAT), H-abstraction, and β-scission), the high reactivity of the alkoxy radical is fine-tuned to promote the selective and challenging formation of a COCH₂CF₃ bond. This reaction, involving a triplet energy transfer process, allows the concomitant formation of a CN and COAlk bond, so far uncharted, using bifunctional oxime ether reagents. Hence, the difunctionalization of a myriad of electron-rich alkenes selectively afforded the anti-Markovnikov products with a large functional group tolerance (44 examples, up to 77% yield), offering a straightforward and complementary regioselectivity compared to the existing approaches for the difunctionalization of alkenes with 2,2,2-trifluoroethanol. Post-functionalization reactions and mechanistic investigations provided key insights into the reaction mechanism of this transformation.