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

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. [ABSTRACT FROM AUTHOR]