Room-temperature regioselective c-H/olefin coupling of aromatic ketones using an activated ruthenium catalyst with a carbonyl ligand and structural elucidation of key intermediates

Mechanistic studies of the ruthenium-catalyzed reaction of aromatic ketones with olefins are presented. Treatment of the original catalyst, RuH ₂(CO)(PPh₃)₃, with trimethylvinylsilane at 90 °C for 1-1.5 h afforded an activated ruthenium catalyst, Ru(o-C ₆H₄PPh₂)(H)(CO)(PPh₃)₂, as a mixture of four geometric isomers. The activated complex showed high catalytic activity for C-H/olefin coupling, and the reaction of 2′-methylacetophenone with trimethylvinylsilane at room temperature for 48 h gave the corresponding ortho-alkylation product in 99% isolated yield. The activated catalyst was thermally robust and showed excellent catalytic activity under refluxing toluene conditions. ¹H and ³¹P NMR studies of the C-H/olefin coupling at room temperature suggested that an ortho-ruthenated complex, P,P′-cis-C,H-cis-Ru(2′-(6′-MeC ₆H₄C(O)Me))(H)(CO)(PPh₃)₂, participated in the reaction as a key intermediate. Isotope labeling studies using acetophenone-d₅ indicated that the rate-limiting step was the C-C bond formation, not the C-H bond cleavage, and that each step prior to the reductive elimination was reversible. The rate of C-H/olefin coupling was found to exhibit pseudo first-order kinetics and to show first-order dependence on the ruthenium complex concentration.