Pd(OAc)₂/AgOAc Catalytic System Based Bidentate Ligand Directed Regiocontrolled C–H Arylation and Alkylation of the C‐3 Position of Thiophene‐ and Furan‐2‐carboxamides

Abstract

Abstract A contemporary method is reported for the Pd(OAc) 2 /AgOAc catalytic system based bidentate ligand directed, regioselective C–H activation and C–C bond formation at the C‐3 position of thiophene‐ and furan‐2‐carboxamides, which are derived from 8‐aminoquinoline or 2‐(methylthio)aniline. The Pd‐catalyzed C–H arylation of thiophene‐ and furan‐2‐carboxamides with a variety of aryl iodides and heteroaryl iodides was highly regioselective and afforded C‐3‐arylated thiophene‐2‐carboxamides and furan‐2‐carboxamides in good to very good yields. The bidentate ligand directed Pd(OAc) 2 /AgOAc based strategy was also successfully employed for benzylation and alkylation reactions of the thiophene‐2‐carboxamides. These reactions occurred with high regioselectivity to afford the C‐3‐benzylated and C‐3‐alkylated thiophene‐2‐carboxamides in good yields. The observed regioselectivity of these reactions was confirmed by X‐ray crystal structure analyses of compounds 3e , 5a , and 6a .