Exploring 1,3-Dipolar Cycloaddition Reactions of Nitrones with Alkenes: Synthesis of Isoxazolidine Derivatives

Abstract

Heterocycles have long been pivotal to the advancement of organic chemistry, forming the backbone of numerous compounds with significant chemical, biological, and industrial applications. Among these, isoxazolidines (ISXs) hold particular importance due to their versatility in generating diverse molecular architectures. A prominent synthetic route to ISXs involves the 1,3-dipolar cycloaddition (1,3-DC) of nitrones with alkenes, a reaction valued for its ability to construct chiral molecules with multiple stereogenic centers. The pharmaceutical industry's growing demand for enantiopure compounds has spurred extensive research into asymmetric synthesis, particularly in the context of 1,3-DC reactions. Despite notable advancements, controlling regio-, diastereo-, and enantioselectivity in these reactions remains a significant challenge. This review provides a focused bibliographic overview of nitrone-alkene cycloaddition reactions, highlighting key developments and current challenges in achieving selectivity.