A copper-catalyzed reductive cross-coupling reaction of aryl chlorides and aryl bromides

In this study, we report a copper-catalysed reductive electrophilic cross-coupling reaction that enables the direct formation of C-C bonds between aryl chlorides and aryl bromides under reductive conditions. Unlike classical cross-coupling reactions that rely on pre-synthesised organometallic reagents, this method employs Cu(OTFA)₂ as the catalyst, (4R,4'R)-2,2'-methylenebis[4,5-dihydro-4-(phenylmethyl)oxazole] (BOX) as the ligand, and MeMgBr as the reducing agent, with K₂CO₃ added as an additive. This catalytic cycle begins with the formation of the Cu-BOX complex and proceeds via fundamental steps such as oxidative addition, metallation and reductive elimination. The chiral BOX ligand modulates the electronic character of the copper centre, enabling efficient and selective cross-reductive coupling between two electrophilic aryl reagents. The reaction can be carried out under mild conditions, exhibiting high chemical selectivity and a broad substrate scope. The corresponding biaryl product yields are as high as 93%. This study provides a novel and sustainable method for the copper-catalysed reductive cross-coupling of two aryl halides to construct C(sp²)-C(sp²) bonds, expanding synthetic strategies and facilitating the acquisition of structurally diverse biaryl units relevant to materials science and drug research.