Scope and Mechanistic Investigations on the Solvent-Controlled Regio- and Stereoselective Formation of Enol Esters from the Ruthenium-Catalyzed Coupling Reaction of Terminal Alkynes and Carboxylic Acids.

Abstract

The ruthenium-hydride complex (PCy(3))(2)(CO)RuHCl was found to be a highly effective catalyst for the alkyne-to-carboxylic acid coupling reaction to give synthetically useful enol ester products. Strong solvent effect was observed for the ruthenium catalyst in modulating the activity and selectivity; the coupling reaction in CH(2)Cl(2) led to the regioselective formation of gem-enol ester products, while the stereoselective formation of (Z)-enol esters was obtained in THF. The coupling reaction was found to be strongly inhibited by PCy(3). The coupling reaction of both PhCO(2)H/PhC identical withCD and PhCO(2)D/PhC identical withCH led to the extensive deuterium incorporation on the vinyl positions of the enol ester products. An opposite Hammett value was observed when the correlation of a series of para-substituted p-X-C(6)H(4)CO(2)H (X = OMe, CH(3), H, CF(3), CN) with phenylacetylene was examined in CDCl(3) (rho = +0.30) and THF (rho = -0.68). Catalytically relevant Ru-carboxylate and -vinylidene-carboxylate complexes, (PCy(3))(2)(CO)(Cl)Ru(kappa(2)-O(2)CC(6)H(4)-p-OMe) and (PCy(3))(2)(CO)(Cl)RuC(=CHPh)O(2)CC(6)H(4)-p-OMe, were isolated, and the structure of both complexes was completely established by X-ray crystallography. A detailed mechanism of the coupling reaction involving a rate-limiting C-O bond formation step was proposed on the basis of these kinetic and structural studies. The regioselective formation of the gem-enol ester products in CH(2)Cl(2) was rationalized by a direct migratory insertion of the terminal alkyne via a Ru-carboxylate species, whereas the stereoselective formation of (Z)-enol ester products in THF was explained by invoking a Ru-vinylidene species.