Facile synthesis of spiro-heterocycles through one-pot multicomponent [3 + 3] cross 1,3-dipolar cycloaddition reactions

Abstract

A three-component 1,3-dipolar cycloaddition reaction involving ninhydrin, proline, and nitrile imines, which are generated in situ from hydrazonoyl chlorides, has been developed. This transformation can be conceptualized as a cross-1,3-dipolar cycloaddition reaction between two distinct ylides, proceeding via a [3 + 3] annulation pathway. This approach offers a swift route to a diverse array of novel and structurally intricate spiro-multiheterocyclic skeletons, achieving good yields ranging from 80 % to 94 %. Furthermore, the chemical structure of a representative product has been rigorously confirmed via X-ray diffraction analysis.