Unlocking Reactivity of Unprotected Oximes via Green‐Light‐Driven Dual Copper/Organophotoredox Catalysis

Oximes are widely used precursors in synthetic chemistry due to their broad availability and versatile chemical properties, in which N-O bond fragmentation represents a key reactivity mode. However, these transformations typically require the use of oxygen-protected oximes, and a general strategy to directly utilize free oximes remains challenging due to their vulnerability to side reaction pathways, rendering low tendency towards N-OH bond cleavage. Here we report a unified platform to achieve direct cyclization of unprotected oximes with enals, as well as other coupling partners through dual copper/organophotoredox catalysis under green light irradiation. This protocol enables concurrent activation of both N-OH and α-C(sp3)-H bonds of free oximes to form multisubstituted pyridines with exceeding structural diversity and high functional group tolerance. In this process, the photocatalyst (Rose Bengal) also serves as a hydrogen atom transfer agent to generate radical intermediates. In the meanwhile, copper catalyst activates free oximes via single-electron reduction induced N-O bond fragmentation, and controls the selectivity for intermediate trapping. The synthetic utility of this approach is further demonstrated by its successful applications in late-stage modification of biologically active compounds and rapid assembly of solvatochromic fluorescent materials.