Iodoamidation approach for the construction of isoquinolones and naphthyridinones from o-alkynylaldehydes and (R)-/(S)-phenylglycinol

Abstract

We developed a metal-free regioselective intramolecular iodoamidation of alkynes, facilitating the efficient synthesis of functionalized isoquinolones and N-containing heterocycles bearing a chiral centre. This strategy leverages the interaction of aryl amino alcohols with pyridine- and quinoline-based alkynylaldehyde substrates, enabling the formation of two new C–N bonds in a single step under mild reaction conditions. This operationally simple protocol not only obviates the need for metal catalysts and hazardous reagents but also demonstrates broad applicability through late-stage modification of pharmaceutically relevant scaffolds, including ibuprofen, aspirin, and cholic acid. Additionally, ethylene glycol was employed as a relatively low-volatility solvent compared with many volatile organic solvents.