Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α‐Arylation of Alcohols through Photoredox, HAT, and Nickel Catalysis. Issue 19 (6th April 2018) - Twilton, Jack
Abstract: The combination of nickel metallaphotoredox catalysis, hydrogen atom transfer catalysis, and a Lewis acid activation mode, has led to the development of an arylation method for the selective functionalization of alcohol α‐hydroxy C−H bonds. This approach employs zinc‐mediated alcohol deprotonation to activate α‐hydroxy C−H bonds while simultaneously suppressing C−O bond formation by inhibiting the formation of nickel alkoxide species. The use of Zn‐based Lewis acids also deactivates other hydridic bonds such as α‐amino and α‐oxy C−H bonds. This approach facilitates rapid access to benzylic alcohols, an important motif in drug discovery. A 3‐step synthesis of the drug Prozac exemplifies the utility of this new method. Abstract : The power of three : A triple catalysis method was developed for C−C bond formation at the α‐carbon of alcohols using aryl halide electrophiles. This method provides generic access to a broad range of benzylic and heteroaryl benzylic motifs. A new strategy for the selective functionalization of alcohols by leveraging a Lewis acid additive was utilized to enable selective hydrogen atom transfer at the α‐carbon and suppress competing C−O coupling.