Catalytic cross-electrophile coupling of aryl chlorides with unactivated alkyl chlorides: The synergy of iron and Li

Summary

The example of iron-catalyzed cross-electrophile coupling of aryl chlorides with unactivated alkyl chlorides via an iron/B₂pin₂ catalytic system has been developed. (Hetero)aryl chlorides undergo this transformation smoothly under mild conditions, furnishing the alkylated products with good efficiency. This protocol features excellent functional group compatibility and gram-scale synthesis, which also enables the late-stage functionalization of bioactive molecules, thus offering excellent opportunities for the development of medicinal chemistry. Preliminary experiments and computational studies suggest that the reaction may involve the Fe⁰/Fe^II/Fe⁰/Fe^I catalytic cycle. The synergy of two Li with iron is crucial to the activation of aryl-Cl and alkyl-Cl through oxidative addition and cation-assisted single-electron transfer pathway.