Recent progress in the construction of eight-membered nitrogen-heterocycles

Abstract

Eight-membered ring skeletons are widely present in a variety of natural products and bioactive molecules. In particular, eight-membered nitrogen-heterocycles are compelling privileged structures for drug discovery, especially for challenging targets that are difficult to modulate using conventional small molecule screening libraries. However, the construction of eight-membered N-heterocycles is a formidable challenge in chemistry owing to unfavorable entropic and enthalpic effects. Thus, the development of novel strategies to access these scaffolds is highly desirable. In this review, we summarize the progress in the synthesis of eight-membered N-heterocycles in the past 20 years (1995–2023), with a focus on reaction mechanisms associated with typical reactions. We aim to inspire synthetic chemists to develop efficient strategies for the construction of eight-membered N-heterocycles.