Photocatalytic construction of seven-membered aza-heterocycles: Recent advances and mechanistic insights

Abstract

Alkaloids containing seven-membered aza-heterocyclic scaffolds represent a privileged class of natural products with diverse pharmacological activities, driving continuous demand for efficient synthetic routes toward these frameworks. In the context of green and sustainable chemistry, organic photochemical synthesis has emerged as a powerful platform for aza-heterocycle construction, enabling mild and selective access to reactive intermediates through photoexcited-state pathways that are orthogonal to conventional thermal methods. While photochemical synthesis of five- and six-membered aza-heterocycles has been extensively explored, construction of the thermodynamically more disfavored seven-membered analogues remains relatively underdeveloped. This feature article reviews the state-of-the-art progress in photochemical synthesis of seven-membered aza-heterocycles from 2023 onward, categorizing methodologies into (1) tandem radical addition–cyclization, (2) dearomative cycloaddition, (3) ring-expansion skeletal editing, and (4) miscellaneous approaches. With a particular emphasis on reaction mechanisms and strategic design principles, this work aims to serve as a timely reference for synthetic chemists and to inspire innovations targeting medicinally relevant aza-heterocycles.