Amide-directed photoredox-catalysed C–C bond formation at unactivated sp3 C–H bonds

The formation of carbon–carbon bonds is achieved via directed cleavage of traditionally non-reactive carbon–hydrogen bonds and their subsequent coupling with readily available alkenes. In two separate reports, Robert Knowles and colleagues, and John Chu and Tomislav Rovis report the selective homolysis of selected amidyl N–H bonds through a photocatalytic proton-coupled electron-transfer process. The resulting radical enables C–H abstraction and radical alkylation at the unactivated 5 position on the aliphatic chain of the N-alkyl amide. As this method does not rely on pre-activation of the amidyl N–H bond or the use of haloamides, it offers a potentially simpler solution than previous approaches to radical amidyls. Additionally, the subsequent 1,5-hydrogen-atom transfer offers a route to selective C–C bond formation in the presence of alkyl amides. Carbon–carbon (C–C) bond formation is paramount in the synthesis of biologically relevant molecules, modern synthetic materials and commodity chemicals such as fuels and lubricants. Traditionally, the presence of a functional group is required at the site of C–C bond formation. Strategies that allow C–C bond formation at inert carbon–hydrogen (C–H) bonds enable access to molecules that would otherwise be inaccessible and the development of more efficient syntheses of complex molecules1,2. Here we report a method for the formation of C–C bonds by directed cleavage of traditionally non-reactive C–H bonds and their subsequent coupling with readily available alkenes. Our methodology allows for amide-directed selective C–C bond formation at unactivated sp3 C–H bonds in molecules that contain many such bonds that are seemingly indistinguishable. Selectivity arises through a relayed photoredox-catalysed oxidation of a nitrogen–hydrogen bond. We anticipate that our findings will serve as a starting point for functionalization at inert C–H bonds through a strategy involving hydrogen-atom transfer.