PALLADIUM-CATALYZED CYCLOCARBONYLATION OF ACETYLENIC ALCOHOLS TO METHYLENE LACTONES - SCOPE AND SYNTHESIS OF APPROPRIATE SUBSTRATES

Methylene lactones are available by catalytic cyclocarbonylation of the ethynyl alcohols resulting from epoxidation and ethynylation of olefins. Dimethylethynylaluminum etherate in toluene is useful for the ethynylation of base-sensitive epoxides. Trans cycloalkanols can be converted to their cis isomers either by oxidation and stereoselective reduction or by epimerization of the corresponding tosylate. The best cyclocarbonylation catalyst system has proved to be PdCl2, anhydrous SnCl2, and 2 equiv of a tertiary phosphine in CH3CN. A wide variety of methylene lactones, including both cis and trans fused-ring systems, can be made from the appropriate ethynyl alcohol precursors if the substrate concentration is kept sufficiently low to favor cyclization over intermolecular reaction. Incipient ring strain, although it lowers the yield of methylene lactones, does not affect the rate of consumption of starting material, as demonstrated by the competitive cyclocarbonylation of 3c and 5c. This observation suggests that the formation of a carboalkoxy intermediate from the catalyst and the substrate alcohol is irreversible.