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-acyl oxy-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 rearrang ement of the monoesters 3 to allenic intermediates 4, followed by Ag(I)-ass isted cyclization. A stereochemical analysis revealed that the newly formed carbon-oxygen bond in 5 was formed from the back side of the cleaved carbo n-oxygen bond in 3. The propargyl esters 3 were prepared by an enantioselec tive reduction of the corresponding alkynyl ketones 1, followed by acylatio n. Since 3-acyloxy-2,5-dihydrofurans 5 were easily converted to the corresp onding 4,5-dihydro-3(2H)-furanones 6, this sequence was successfully applie d to the synthesis of a differentiation-inducing antibiotic, (S)-(-)-ascofu ranone.