MgCl2-mediated activation of C-5 alkyl coumalates in aqueous medium for the synthesis of [2.2.2]-bicyclic lactones via DAINV reaction

Abstract

This work represents a straightforward protocol for converting the less reactive C-5 alkyl coumalates especially renewable, bio-based and non-hazardous feedstock methyl coumalate into essential synthetic motifs. In this protocol, magnesium chloride (MgCl₂) salt efficiently activated the less reactive C-5 alkyl coumalates for DA_INV reaction with electron-rich vinyl ethers as dienophiles to produce [2.2.2]-bicyclic lactones. Water, being a green solvent, produced the best results among all the tested solvents in terms of the rate of reaction and yield of the product. The substrate scope was explored by varying the alkyl coumalates and vinyl ethers, which afforded the corresponding products in high yields (up to 95%) and good diastereoselectivities (up to >99%) with endo preference.