Palladium-catalyzed intramolecular hydroalkylation of alkenyl-beta-keto esters, alpha-aryl ketones, and alkyl ketones in the presence of Me3SiCl or HCl

Reaction of 3-butenyl beta-keto esters or 3-butenyl alpha-aryl ketones with a catalytic amount of PdCl2(CH3CN)2] (2) and a stoichiometric amount of Me3SiCl or Me3SiCl/CuCl2 in dioxane at 25-70 degrees C formed 2-substituted cyclohexanones in good yield with high regioselectivity. This protocol tolerated a number of ester and aryl groups and tolerated substitution at the allylic, enolic, and cis and trans terminal olefinic positions. In situ NMR experiments indicated that the chlorosilane was not directly involved in palladium-catalyzed hydroalkylation, but rather served as a source of HCl, which presumably catalyzes enolization of the ketone. Identification of HCl as the active promoter of palladium-catalyzed hydroalkylation led to the development of an effective protocol for the hydroalkylation of alkyl 3-butenyl ketones that employed sub-stoichiometric amounts of 2, HCl, and CuCl2 in a sealed tube at 70 degrees C.