Diastereoselective synthesis of tetrahydropyrrolo[1,2-d]oxadiazoles from functionalized Δ1-pyrrolines and in situ generated nitrile oxides.

Abstract

Tetrahydropyrrolo[1,2-d]oxadiazoles have been synthesized in good-to-excellent yields via the cycloaddition of nitrile oxides (in situ generated from aldoximes) to readily accessible functionalized Δ1-pyrrolines. The reaction proceeds smoothly at room temperature in a two-phase system in the presence of sodium hypochloride as an oxidant to diastereoselectively afford pharmaceutically prospective 1,2,4-oxadiazolines fused with a five-membered ring. The reaction tolerates a broad range of substrates, including those with oxidant-sensitive functional groups and competitive reaction sites.