Development, scope, and mechanism of the palladium-catalyzed intramolecular hydroalkylation of 3-butenyl β-diketones

Reaction of 7-octene-2,4-dione (3) with a catalytic amount of PdCl 2(CH 3CN) 2 (4) (10 mol %) in dioxane at room temperature for 16 h formed 2-acetylcyclohexanone (5) in 81% yield as a single regioisomer. Byproducts in the conversion of 3 to 5 include 2,4-octanedione (13), 2-acetyl-2-cyclohexenone (14), 2-acetylphenol (15), (Z)- and (Z)-6-octene-2,4-dione (17), (E)-and (Z)-5-octene-2,4-dione (18), the η 3-ß-diketonate chloride dimer {η 3-CH 3CH 2CH 2-CHCOHCHAc]Pd(Cl)} 2 (12), and the π(allyl)palladium chloride dimer {[η 3-CH 3CHCHCHC-(O)CH 2Ac]Pd(Cl)} 2 (16). The palladium-catalyzed cyclization of 3-butenyl β-diketones tolerated substitution at the terminal acyl carbon atom, the enolic carbon atom, and the terminal olefinic carbon atom. Deuterium-labeling studies, in conjunction with kinetic and in situ NMR experiments, supported a mechanism for the palladium-catalyzed hydroalkylation of 3-butenyl β-diketones initiated by 6-endo-trig attack of the enol carbon atom on a palladium-complexed olefin to form a palladium cyclohexanone species. Migration of the palladium atom from the C(4) to the C(6) carbon atom of the 2-acylcyclohexanone intermediate via iterative β-hydride elimination/addition followed by protonolysis of the resulting palladium C(6)-enolate complex released the cyclohexanone and regenerated the palladium dichloride catalyst.

Duke Scholars

Author Ross A. Widenhoefer Chemistry