Metallaphotoredox-enabled deoxygenative arylation of alcohols

Metal-catalysed cross-couplings are a mainstay of organic synthesis and are widely used for the formation of C–C bonds, particularly in the production of unsaturated scaffolds 1 . However, alkyl cross-couplings using native sp 3 -hybridized functional groups such as alcohols remain relatively underdeveloped 2 . In particular, a robust and general method for the direct deoxygenative coupling of alcohols would have major implications for the field of organic synthesis. A general method for the direct deoxygenative cross-coupling of free alcohols must overcome several challenges, most notably the in situ cleavage of strong C–O bonds 3 , but would allow access to the vast collection of commercially available, structurally diverse alcohols as coupling partners 4 . We report herein a metallaphotoredox-based cross-coupling platform in which free alcohols are activated in situ by N-heterocyclic carbene salts for carbon–carbon bond formation with aryl halide coupling partners. This method is mild, robust, selective and most importantly, capable of accommodating a wide range of primary, secondary and tertiary alcohols as well as pharmaceutically relevant aryl and heteroaryl bromides and chlorides. The power of the transformation has been demonstrated in a number of complex settings, including the late-stage functionalization of Taxol and a modular synthesis of Januvia, an antidiabetic medication. This technology represents a general strategy for the merger of in situ alcohol activation with transition metal catalysis. A metallaphotoredox-based cross-coupling platform is capable of activating a wide range of free alcohols using N-heterocyclic carbene salts, cleaving C–O bonds to form free carbon radicals that are then used to form new C–C bonds.