One-Step Rh-Catalyzed Atom-Economical Cyclization of Acetophenones and Methyl Propiolate Affording Isoquinoline Derivatives

Isoquinoline derivatives hold significant importance in the fields of natural product chemistry, medicinal chemistry, and biological sciences. Currently, researchers are actively exploring efficient and general synthetic methodologies for these compounds. Herein, we report the use of hydroxylamine-O-sulfonic acid (HOSA) as a novel transient directing group (TDG) to enable the selective ortho–C-H functionalization/cyclization of acetophenones with methyl propiolate. This strategy allows for the one-pot synthesis of isoquinoline derivatives under mild and easily tunable conditions. The type of transient directing group, solvent, and oxidant are key factors dictating the reaction pathway, enabling precise control over the product selectivity. The established protocol exhibits a broad substrate scope and excellent functional group tolerance. This study demonstrates that HOSA can serve as a catalytic transient directing group with high conversion efficiency and wide applicability for selective C–H cyclization reactions, and this method holds broad synthetic utility.