An electrochemical γ-C-H arylation of amines in continuous flow

Reported here is a regioselective C(sp(3))-C(sp(2)) cross coupling reaction between inert gamma-C(sp(3))-H bonds in aliphatic amines and cyanoarenes under electrochemical conditions in flow. The developed methodology takes advantage of a removable redox active auxiliary, which triggers selective 1,7-hydrogen atom transfer to functionalise an aliphatic C-H bond at the gamma-position of an alkyl amine. In this reaction, a cyanoarene radical anion functions as both a selective arylating reagent and a redox active mediator, enabling the controlled one electron reduction of the redox active auxiliary. This strategy offers a new approach towards gamma-C(sp(3))-H bond functionalisation allowing generation of, amongst others, sterically crowded carbon centres under mild reaction conditions and in the absence of additional catalysts or radical initiators. (C) 2022 Elsevier Ltd. All rights reserved.