Journal of the American Chemical Society, Vol.117, No.7, 1888-1899, 1995
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. Among various ruthenium complexes, CpRu(COD)Cl appears to be most effective. The best results occur in aqueous DMF or methanol, with the latter preferred. The reaction proceeds with excellent chemoselectivity. Even nonreacting double bonds do not isomerize. The regioselectivity with respect to the alkene is with clean allyl inversion, i.e., in Alder-ene-type fashion. The regioselectivity with respect to the alkyne places the allyl group preferentially at the ct-carbon in complete contrast to more normal behavior of alkynoates wherein P-alkylation strongly dominates. The sequence retains the stereochemical integrity of the propargylic position of the starting alkyne which becomes the 5-position of the product 2(5H)-furanones, a position prone to epimerization. Use 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 sensitive enones which are the normal Michael accepters. The ready availability of 3-hydroxy-2-alkynoates by carbonyl addition of lithiated ethyl propiolate makes this approach to butenolides very practical. The addition of the latter to epoxides in the presence of BF3.OEt(2) provides ready access to 5-hydroxy-2-alkynoates. These substrates participate in a completely analogous fashion as above to form alpha-allylated and alpha-ketoethylated pentenolides. The mechanism of the reaction may be rationalized as invoking a ruthenacycle where coordinating and unusual electronic effects account for the observed selectivity. A synthesis of the simple acetogenin (+)-ancepsenolide results from commercially available 10-undecenal and methyl (S)-lactate in seven steps with 31% overall yield. This synthesis establishes the stereochemistry of this natural product as S,S.