Synthesis of Enantiomerically Enriched 2,5-Dihydrofuran Derivatives from Easily Available Enantiomerically Enriched 2-Butyne-1,4-diols by Stereospecific Transformation

The transformation of enantiomerically enriched 1,1,4-trisubstituted 4-acyloxy-2-butyn-1-ols 3 into 2,2,5-trisubstituted 3-acyloxy-2,5-dihydrofurans 5 with complete stereospecificity was achieved by an Ag(I)-mediated rearrangement of the monoesters 3 to allenic intermediates 4, followed by Ag(I)-assisted cyclization. A stereochemical analysis revealed that the newly formed carbon–oxygen bond in 5 was formed from the back side of the cleaved carbon–oxygen bond in 3. The propargyl esters 3 were prepared by an enantioselective reduction of the corresponding alkynyl ketones 1, followed by acylation. Since 3-acyloxy-2,5-dihydrofurans 5 were easily converted to the corresponding 4,5-dihydro-3(2H)-furanones 6, this sequence was successfully applied to the synthesis of a differentiation-inducing antibiotic, (S)-(−)-ascofuranone.