Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct alpha-Arylation of Alcohols through Photoredox, HAT, and Nickel Catalysis

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 -hydroxy C-H bonds. This approach employs zinc-mediated alcohol deprotonation to activate -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 -amino and -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.