Electrochemical regioselective synthesis of sulfonyl 2,5-dihydrofuran-fused spiropyrimidines via multi-component radical cascade reactions

Abstract

In this work, we developed an efficient and environmentally friendly electrochemical three-component one-pot method for the generation of polysubstituted 2,5-dihydrofuran-fused spiropyrimidines containing valuable functional groups (–SO₂R, –OR) that are difficult to access traditionally. In addition to water, various O-nucleophilic agents such as alcohols, carboxylates, and deuterium oxide can be seamlessly incorporated in one synthetic step. This protocol features a broad substrate scope (72 examples, up to 97% yield), excellent functional group compatibility, high regio- and diastereoselectivity, straightforward operation, and easy scalability, establishing it as a green and versatile method for constructing heterocycle-tethered spiropyrimidines. The mechanistic investigation reveals that the reaction proceeds via a cascade sulfonyl radical addition, 5-exo-trig ipso-cyclization, anodic oxidation, and subsequent nucleophilic attack process.