Chemo‐ and Regioselective Catalytic Cross‐Coupling Reaction of Ketones for the Synthesis of β, γ‐Disubstituted β, γ‐Unsaturated Ketones

C‐C bond forming reaction of ketone with aldehyde is well‐studied for the synthesis of α, β‐unsaturated ketones, however, the reaction with two different ketones to unsaturated carbonyl compound has not yet been systematically studied. Probably due to the relatively low reactivity of ketones as electrophiles (aldol acceptors), its propensity for retro‐aldol reaction. The reactions often suffer from unsatisfactory chemoselectivity. In this quest, we report here for the first time selective cross‐coupling reaction of ketones to β‐branched β, γ‐unsaturated ketones by using ruthenium catalysis. Interestingly, single crossed aldol condensation products are formed even in reactions where a mixture of products is possible. Reaction is highly chemoselective, regioselective and produces H2O as the only byproducts. Method is compatible with a wide variety of sensitive functional group and applicable for even problematic aliphatic ketones as substrates. Notably, acetone was found as a three‐carbon feedstock for the syntheses of simple β, γ‐unsaturated ketones. The process can further be extended to the late‐stage functionalization of natural products. With the help of DFT calculations, and several control experiments, the mechanistic finding demonstrated that initial aldol‐condensation of ketones to α, β‐unsaturated ketone, which further isomerizes to a β, γ‐ unsaturated ketone via η3‐allyl ruthenium complex.