Cobalt-Photoredox-Catalyzed C–H Annulation of N -Aryl Benzamides with 2,5-Dihydrofuran: Double Stereo Induction

Abstract

The resurgence of photocatalysis, a green, eco-friendly strategy that harnesses light to enable valuable organic transformations, offers a blueprint for developing green synthetic methodologies for the synthesis of chiral molecules via enantioselective C–H activation. Although there are several methods for single-chirality induction, multi stereo-element induction with photoredox remains underexplored. Herein, we report an effective one-step method for inducing central and C–N axial chirality via photoredox-mediated C–H annulation of benzamides. This methodology avoids the stoichiometric amount of metal oxidant, and the reaction proceeds under mild reaction conditions. This photoredox strategy enables C–H annulation of various benzamides with good functional group tolerance, affording central and atropo-chiral products with high enantio- and diastereoselectivity (28 examples, up to >99% ee and >20:1 dr). Catalytic and stoichiometric reactions with a cobaltacycle suggested its involvement in the catalytic cycle and potential role in enantiocontrol. The gram-scale reaction demonstrates the practicality of the developed protocol. Notably, both the solvent and the ligand can be recovered and reused, highlighting the potential sustainability of the developed methodology.