Catalyst-Free Selective Synthesis of E-Tetrasubstituted Olefins via Tandem Reaction of 3-Acetyl-4-phenyl-1-oxaspiro[4.5]deca-3,6,9-triene-2,8-dione with Amine, C–C Bond Breakage, and Proton Transfer

Abstract

The Z- or E-selective syntheses of tetrasubstituted olefins present big challenges. Tremendous efforts are ongoing to overcome this issue, especially for acyclic structures. In this work, an E-stereoselective synthetic method of tetrasubstituted olefins through tandem reaction of 1,4-Michael addition of 3-acetyl-4-phenyl-1-oxaspiro[4.5]deca-3,6,9-triene-2,8-dione with amine, C–C bond breakage, and proton transfer by intermolecular hydrogen bonds was revealed with excellent atom economy and without catalysts and additives. A diverse set of E-tetrasubstituted olefins were obtained in 43% to 93% yields with excellent functional group tolerance for late-stage modifications of complex drug molecules. The reaction mechanism was proposed based on the deuterium-labeling experiment and density functional theory (DFT) calculation.