CuI-promoted domino Sonogashira coupling and alkyne Hydroamination of Benzofuran-fused Benzimidazoles: Synthesis and antimicrobial insights.

A novel sequential strategy involving copper-catalyzed cascade Sonogashira coupling followed by intramolecular acetylene hydroamination was developed, providing a modular and convenient approach for the synthesis of benzo[d]benzofuro[2',3',3,4]pyrrolo[1,2-a]imidazole derivatives (6a-p). Sixteen structurally diverse derivatives were synthesized by reacting 2-(3-chlorobenzofuran-2-yl)-1H-benzo[d]imidazole with various substituted terminal alkynes, affording the desired compounds in moderate to high yields (up to 83 %). In vitro antimicrobial screening of newly synthesized compounds was carried out against four bacterial (Staphylococcus aureus; Bacillus subtilis; Pseudomonas aeruginosa; and Salmonella typhi) and two fungal strains (Fusarium and Mucor). Among them, compounds 6c-g, 6i, 6j, 6m and 6o were found to be most active against bacterial strains, and compounds 6c, 6j, and 6l displayed maximum activity against fungal strains. The protocol tolerates a broad range of functional groups and facilitates the formation of C(sp)-C(sp2) and CN bonds in a single operational step. The use of a cost-effective copper catalyst strengthens the green credentials of the approach. The selective mechanistic route enables the synthesis of structurally diverse fused heterocyclic frameworks with significant pharmaceutical relevance. Additionally, the structure-activity relationship of the titled compounds reveals how the inclusion of distinct functional groups can influence their antimicrobial potency, either positively or negatively.