Enantioselective synthesis of α-hydroxylated enterolactone and analogs

A short and general synthesis of enantiomerically pure α-hydroxylated lactone lignans starting from commercially available iPr malate is presented. Key reactions are two stereoselective alkylations of malic acid derivatives. Some enhancements of the alkylation of malic acid esters and a general extension of the alkylation of dioxolanones is reported. Proof of the stereochemical outcome of the alkylation reactions is provided by X-ray diffraction analysis of α-hydroxy-α,β-dibenzyl-γ-butyrolactone, the first crystal structure of an enantiomerically pure α-hydroxylated lactone lignan.