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 3 CN) 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 ), ( E )- and ( Z )-6-octene-2,4-dione ( 17 ), ( E )- and ( Z )-5-octene-2,4-dione ( 18 ), the η 3 -β-diketonate chloride dimer {[η 3 -CH 3 CH 2 CH 2 CHCOHCHAc]Pd(Cl)} 2 ( 12 ), and the π(allyl)palladium chloride dimer {[η 3 -CH 3 CHCHCHC(O)CH 2 Ac]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.