Exploring azetidine containing heterocycles: From green synthesis to applications

Abstract

Azetidine is a four-membered nitrogen-containing saturated heterocycle that has received significant attention in organic and medicinal chemistry research. Various FDA-approved drugs such as azelnidipine, cobimetinib, ximelagatran, and baricitinib contain azetidine moiety. The synthetic versatility of azetidine has been explored less due to its strained ring system. In the last decades, scientists have been working to advance their synthetic feasibility via greener routes. Thus, this review sheds light on the various green synthetic methodologies to achieve azetidine heterocycles, focusing on the high yield, stereoselective, and mild solvent/reaction medium. Importantly, an essential aspect of each synthetic strategy has been highlighted, which delves excellent insight into the desired transformation. Further, this review explores the versatile application of azetidine-based ligands in coupling reactions, asymmetric catalysis, and explosive materials. Besides, synthetic routes to FDA-approved azetidine-heterocycles have been reported, which commence the development of novel azetidine heterocycles with broader applications.