Boryl radical-mediated halogen-atom transfer enables arylation of alkyl halides with electrophilic and nucleophilic coupling partners

Abstract

Traditional metal-catalysed cross-couplings of alkyl halides for C(sp3)–C(sp2) bond formation are often challenging to achieve. Processes where the alkyl halide is initially converted into a radical species can provide valuable complementarity. So far, these strategies are almost exclusively orchestrated by silicon-based reagents, which can be expensive, have low atom economy and are sensitive to steric factors. Here we report the use of the stable Lewis acid–Lewis base complex Me3N–BH3, which, upon conversion into its corresponding amine-ligated boryl radical, enables nickel- and copper-catalysed cross-coupling of alkyl iodides and bromides with electrophilic aryl bromides and nucleophilic aryl boronic acids. Mechanistically, this method uses the amine borane radical’s propensity to activate halides via halogen-atom transfer through highly polarized transition states. This reactivity features mild conditions and broad tolerability of functional groups and engages sterically hindered alkyl halides. The use of alkyl halides in radical cross-couplings generally requires silicon reagents as halogen abstractors. Now Me3N–BH3 is reported to facilitate these couplings with both aryl bromides and aryl boronic acids under either nickel or copper catalysis.