Electrochemical-induced benzyl C-H amination towards the synthesis of isoindolinones via aroyloxy radical-mediated C-H activation

The rapid synthesis of valuable isoindolinones with cheap and easily available starting materials under mild conditions is of great importance, but is challenging. We enclose here a novel electrochemical strategy to selectively and sustainably access isoindolinone using simple o-alkyl benzoic acids and nitriles as substrates under metal catalyst and external oxidant-free conditions. The protocol shows a very good functional group tolerance. Mechanistic investigations suggest that aroyloxy radicals are involved in this transformation, which initiates the benzylic C-H amination event by a 1,5-HAT process. Meanwhile, nitrile as the nitrogen source plays a vital role, as its derived intermediate facilitates the construction of the amide bond in the product.

Automated summary

A novel electrochemical strategy is proposed to selectively and sustainably synthesize isoindolinones using simple o-alkyl benzoic acids and nitriles as substrates under metal catalyst and external oxidant-free conditions. The protocol exhibits good functional group tolerance and the nitrile plays a vital role in constructing the amide bond in the product.