Synthesis of 2-alkoxy-5-methylenetetrahydropyrans: A regioselective ruthenium-catalyzed C-C coupling reaction of prop-2-yn-1-ols with allyl alcohol

The carbon-carbon coupling of prop-2-yn-1-ols with allyl alcohol is achieved in the presence of the ruthenium(II) catalyst RuCl(cod)(C5Me5). The coupling reaction is highly regioselective and leads to the HOCR2C(=CH2)CH2CH2CHO isomer and, after cyclization, to either 2-hydroxy- or 2-alkoxy-5-methylenetetrahydropyrans, at room temperature or at 80 degrees C, respectively. It is used for the synthesis of molecules containing two and three tetrahydropyran moieties. The study of a variety of prop-2-yn-1-ols has shown the influence of the substituent at the propargyl carbon on the regioselectivity of the C-C coupling. In the case of tertiary alcohols, the reaction leads to only one cyclic isomer, the 2-alkoxytetrahydropyran whereas with secondary alcohols, a linear isomer is also obtained. The tetrahydropyranols are easily oxidized into lactones.