Organic chemistry

Combinatorial chemistry

Nickel

Hydrogen

Stereochemistry

Hydrogen bond

Deprotonation

Catalysis

Lewis acids and bases

Medicinal chemistry

Chemistry

Alkoxide

Alcohol

Molecule

Photochemistry

Hydrogen atom abstraction

Angewandte Chemie International Edition

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.

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