RUTHENIUM-CATALYZED SYNTHESIS OF BUTENOLIDES AND PENTENOLIDES VIA CONTRA-ELECTRONIC ALPHA-ALKYLATION OF HYDROXYALKYNOATES

The addition of alkenes to 3-hydroxy-2-alkynoates in an Alder-ene-type mode produces butenolides in the presence of a ruthenium catalyst. Am ong various ruthenium complexes, CpRu(COD)Cl appears to be most effect ive. The best results occur in aqueous DMF or methanol, with the latte r preferred. The reaction proceeds with excellent chemoselectivity. Ev en nonreacting double bonds do not isomerize. The regioselectivity wit h respect to the alkene is with clean allyl inversion, i.e., in Alder- ene-type fashion. The regioselectivity with respect to the alkyne plac es the allyl group preferentially at the ct-carbon in complete contras t to more normal behavior of alkynoates wherein P-alkylation strongly dominates. The sequence retains the stereochemical integrity of the pr opargylic position of the starting alkyne which becomes the 5-position of the product 2(5H)-furanones, a position prone to epimerization. Us e of allyl alcohols as the alkene partners introduces a beta-acylethyl group at the alpha-position of the butenolide, a net equivalent of a conjugate addition to a butenolide anion without requiring the very se nsitive enones which are the normal Michael accepters. The ready avail ability of 3-hydroxy-2-alkynoates by carbonyl addition of lithiated et hyl propiolate makes this approach to butenolides very practical. The addition of the latter to epoxides in the presence of BF3.OEt(2) provi des ready access to 5-hydroxy-2-alkynoates. These substrates participa te in a completely analogous fashion as above to form alpha-allylated and alpha-ketoethylated pentenolides. The mechanism of the reaction ma y be rationalized as invoking a ruthenacycle where coordinating and un usual electronic effects account for the observed selectivity. A synth esis of the simple acetogenin (+)-ancepsenolide results from commercia lly available 10-undecenal and methyl (S)-lactate in seven steps with 31% overall yield. This synthesis establishes the stereochemistry of t his natural product as S,S.