Facile N-directed Ru-catalyzed C(3)–H acylation of heterocyclopentadienes with acyl chlorides

Abstract

The selective C3–H functionalization of 2-substituted heterocyclopentadienes (furan, thiophene and pyrrole) remains challenging owing to the typically higher reactivity of the C5–H and C4–H bonds. In this study, we report a facile method for the selective C3–H acylation of pharmaceutically and agrochemically relevant heterocyclopentadienes bearing N-donor directing groups at the 2-position. This approach utilizes readily available aliphatic, aromatic and heteroaromatic acyl chlorides under catalysis by a Ru/PPh₃ system generated in situ from commercially available, bench-stable precursors. The method exhibits broad tolerance toward various N-donor directing groups, including those with unprotected NH moieties potentially susceptible to N-acylation. Preliminary mechanistic studies suggest a reaction pathway involving C–H activation, which is rate-limiting and assisted by the carboxylate anion generated via the partial decomposition of the acyl chloride in a basic medium.