Regioselective (3+2) Cycloaddition Reactions of Zerumbone: Synthesis of Isoxazolines and Spiro-Pyrrolizidino-Oxindoles, Conformational Diversity and Theoretical Insights

Abstract

Regioselective [3+2] cycloaddition reactions of zerumbone with nitrile oxides and azomethine ylides are developed for the first time. Direct functionalization of the C10-C11 double bond in zerumbone is unique. ZI-8, ZI-9, and ZI-10 exhibited substrate-driven dimer formation, whereas ZI-9, and ZI-10 exhibit solid-state conformational variability. Furthermore, the reactivity of the C2-C3 double bond was investigated utilizing azomethine ylide in a three-component strategy. According to theoretical studies, cycloaddition occurs preferentially on the bottom face of double bonds. This work describes a method for site-selective modification of zerumbone and zerumbone epoxide