Oxidative addition of an alkyl halide to form a stable Cu(III) product.

Luo, Yongrui; Li, Yuli; Wu, Jian; Xue, Xiao-Song; Hartwig, John F; Shen, Qilong · Science · 2023

basic_science · Level V

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Abstract

The step that cleaves the carbon-halogen bond in copper-catalyzed cross-coupling reactions remains ill defined because of the multiple redox manifolds available to copper and the instability of the high-valent copper product formed. We report the oxidative addition of α-haloacetonitrile to ionic and neutral copper(I) complexes to form previously elusive but here fully characterized copper(III) complexes. The stability of these complexes stems from the strong Cu-CF<sub>3</sub> bond and the high barrier for C(<i>CF<sub>3</sub></i>)-C(<i>CH<sub>2</sub>CN</i>) bond-forming reductive elimination. The mechanistic studies we performed suggest that oxidative addition to ionic and neutral copper(I) complexes proceeds by means of two different pathways: an S<sub>N</sub>2-type substitution to the ionic complex and a halogen-atom transfer to the neutral complex. We observed a pronounced ligand acceleration of the oxidative addition, which correlates with that observed in the copper-catalyzed couplings of azoles, amines, or alkynes with alkyl electrophiles.