Caging the Chlorine Radical: Chemoselective Photocatalytic C(sp 3 )–H Functionalization Enabled by Terminal Cu–Cl Sites in a Metal–Organic Framework

Hydrogen atom transfer (HAT) mediated by halogen radicals represents a powerful approach for the functionalization of inert C(sp 3 )–H bonds. Chlorine radical (Cl • ), for example, is capable of generating carbon-centered radicals by abstracting strong C–H bonds (H–Cl bond dissociation energy = 103 kcal/mol). However, the chemoselectivity of these transformations typically suffers due to the high reactivity of Cl • . Herein, we disclose a novel strategy employing a metal–organic framework (MOF) to tame Cl • and effect the selective alkylation of C(sp 3 )–H bonds. Under light irradiation, MIT20-LiCl─an anionic Cu(II) MOF containing terminal Cu–Cl sites─undergoes ligand-to-metal charge transfer (LMCT) to generate a Cl • -like species that acts as an HAT mediator. MIT20-LiCl is a superior C(sp 3 )–H alkylation catalyst compared to soluble CuCl 2 and allows for the chemoselective alkylation of alcohols without overoxidation. We further demonstrate that this protocol can be used to facilitate C(sp 3 )–H alkylation of ethers, amines, alcohols, and benzylic sites with broad functional group tolerance. Mechanistic experiments and density functional theory (DFT) calculations support that the framework effectively attenuates the reactivity of Cl • generated within its pores. Further, the heterogeneous MOF catalyst can be easily recycled and used in consecutive reactions without a loss in yield, making it a promising platform for sustainable C(sp 3 )–H functionalization.