Copper-Catalyzed Radical/Radical C(sp 3)-H/P-H Cross-Coupling: α-Phosphorylation of Aryl Ketone O-Acetyloximes

Abstract

The selective radical/radical cross-coupling of two different organic radicals is a great challenge due to the inherent activity of radicals. In this paper, a copper-catalyzed radical/radical C(sp 3)-H/P-H cross-coupling has been developed. It provides a radical/radical cross-coupling in a selective manner. This work offers a simple way toward β-ketophosphonates by oxidative coupling of aryl ketone o-acetyloximes with phosphine oxides using CuCl as catalyst and PCy3 as ligand in dioxane under N2 atmosphere at 130 °C for 5 h, and yields ranging from 47% to 86%. The preliminary mechanistic studies by electron paramagnetic resonance (EPR) showed that, 1) the reduction of ketone o-acetyloximes generates iminium radicals, which could isomerize to α-sp(3) -carbon radical species; 2) phosphorus radicals were generated from the oxidation of phosphine oxides. Various aryl ketone o-acetyloximes and phosphine oxides were suitable for this transformation.

Keywords: C(sp3)P bonds; copper catalysis; oxidative coupling; radical/radical cross-coupling; β-ketophosphonates.