Free radicals were first discovered more than 120 years ago by Gomberg1 and the first radical cross-couplings demonstrated by Kochi in the 1970s (ref. 2). In contrast to widely used polar cross-coupling chemistry to forge C(sp2)–C(sp2) bonds (such as Suzuki, Negishi and Kumada), radical cross-coupling is advantageous when applied to the coupling of saturated systems because of the mild conditions used and enhanced chemoselectivity associated with single-electron chemistry. The ability to use ubiquitous carbon-based fragments (such as carboxylic acids, alcohols, amines and olefins) in cross-coupling has greatly simplified access to various complex molecules3–9. Apart from these advantages, enantiospecific coupling reactions involving free radicals are unknown and generally believed to be challenging because of their near-instantaneous racemization (picosecond timescale)10. As a result, controlling the stereochemical outcome of radical cross-coupling can be achieved only on a case-by-case basis using bespoke chiral ligands11 or in a diastereoselective fashion guided by nearby stereocentres12. Here we show how readily accessible enantioenriched sulfonylhydrazides and low loadings of an inexpensive achiral Ni catalyst can be used to solve this challenge, thereby enabling enantiospecific, stereoretentive radical cross-coupling between enantioenriched alkyl fragments and (hetero)aryl halides without exogenous redox chemistry or chiral ligands. Calculations support the intermediacy of a unique Ni-bound diazene-containing transition state with C–C bond formation driven by loss of N2.
