α,β-Unsaturated diesters: radical acceptors in dialkylzinc-mediated tandem radical addition/aldol condensation. A straightforward synthesis of rac-nephrosteranic acid

Abstract

The sequence involving conjugate radical addition/aldol condensation/lactonization is a high yielding route to di- and tri-substituted γ-lactones starting from fumaric or maleic diesters. The reactions are mediated with dialkylzincs. The domino process relies on the ability of dialkylzinc to transform α-alkoxycarbonylalkyl radicals into zinc enolates. Compared to diethylzinc, dimethylzinc enables the use of a wider range of alkyl radical precursors. In addition, dimethylzinc is a convenient source of methyl radical, which leads to a straightforward synthesis of methylated derivatives related to α-methyl-paraconic acids.