Nickel-Catalyzed Mono-Selective α-Arylation of Acetone with Aryl Chlorides and Phenol Derivatives

Abstract

The challenging nickel-catalyzed mono-α-arylation of acetone with aryl chlorides, pivalates, and carbamates has been achieved for the first time. A nickel/Josiphos-based catalytic system is shown to feature unique catalytic behavior, allowing the highly selective formation of the desired mono-α-arylated acetone. The developed methodology was applied to a variety of (hetero)aryl chlorides including biologically relevant derivatives. The methodology has been extended to the unprecedented coupling of acetone with phenol derivatives. Mechanistic studies allowed the isolation and characterization of key Ni⁰ and Ni^II catalytic intermediates. The Josiphos ligand is shown to play a key role in the stabilization of Ni^II intermediates to allow a Ni⁰ /Ni^II catalytic pathway. Mechanistic understanding was then leveraged to improve the protocol using an air-stable Ni^II pre-catalyst.

Keywords: Josiphos ligands; mechanisms; nickel intermediates; oxidative addition; synthetic methods.