Recent advances in the annulative cyclization of 2-alkynylanilines: transition metal, metal-free, photoredox, and electrochemical approaches

Abstract

2-Alkynylanilines have been recognized as versatile precursors for the efficient construction of complex heterocyclic scaffolds, which has generated tremendous interest in medicinal and materials chemistry. Their complex reactivity has propelled advances in green synthetic strategies, extending beyond traditional transition metal-mediated and metal-free processes to innovative photo- and electrocatalytic methodologies. Each of these methodologies has its own merits: transition metal catalysis provides high reactivity and selectivity, metal-free processes are in line with the principles of green chemistry, and photo- and electrocatalytic processes offer environmentally friendly, mild, and cost-effective alternatives. This review summarizes recent progress in annulation of 2-alkynylanilines with a variety of coupling partners through these three dominant strategies with emphasis on the construction of five- and six-membered N-heterocycles such as indole, indolinone, indazole, cinnoline, quinoline, and quinazoline derivatives. We provide a detailed discussion of key mechanistic insights, the roles of metal catalysts, ligands, and Lewis acid–base mediators, and the role of photo- and electrochemical methods in driving these processes. In addition, we emphasize their application in the construction of substituted quinolines and natural products, several of which possess superior photophysical properties. Through the presentation of an extensive overview, this work seeks to encourage further developments in catalyst design, green synthesis, and the design of functional heterocyclic materials that will be applied in optoelectronics and bioimaging. The review primarily covers studies reported between 2022 and 2025.