Nickel-catalysed direct alkylation of thiophenes via double C(sp³)–H/C(sp²)–H bond cleavage: the importance of KH₂PO₄

Abstract

A Ni-catalyzed oxidative C-H/C-H cross-dehydrogenative coupling (CDC) reaction was developed for constructing various highly functionalized alkyl (aryl)-substituted thiophenes. This method employs thiophenes and aliphatic (aromatic) amides that contain an 8-aminoquinoline as a removable directing group in the presence of a silver oxidant. The approach enables the facile one-step synthesis of substituted thiophenes with high functional group compatibility via double C-H bond cleavage without affecting C-Br and C-I bonds. DFT calculations verify the importance of KH₂PO₄ as an additive for promoting C-H bond cleavage and support the involvement of a Ni(iii) species in the reaction.