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 exhibited solid-state conformational variability. Furthermore, the reactivity of the C2–C3 double bond was investigated utilizing an 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.