Acylation of Five-Membered N-Heteroaromatic Compounds by Ruthenium Carbonyl-Catalyzed Direct Carbonylation at a C−H Bond

The ruthenium-catalyzed carbonylation at the C−H bond of five-membered N-heteroaromatic compounds is described. The reaction of imidazoles with CO and olefins in toluene in the presence of a catalytic amount of Ru3(CO)12 results in carbonylation of the C−H bond at the 4-position (adjacent to the sp2-nitrogen) of the imidazole ring to give acylated imidazoles in good to high yields. A wide range of olefins can be utilized in the carbonylation reaction, and a variety of functional groups are compatible under the reaction conditions. Other five-membered N-heteroaromatic compounds, such as pyrazoles, oxazoles, and thiazoles, can also be used for the carbonylation reaction, and in all cases, carbonylation takes place exclusively at a C−H bond α to the sp2 nitrogen. The reactivity of the five-membered heterocycles corresponds to the pK a of the conjugate acid of these heterocycles. The higher the pK a of the substrate, the higher is the reactivity. This indicates that the pK a values are related to the ability of the nitrogen atom in the substrates to coordinate to a ruthenium center. The coordination of the substrates to the ruthenium center in the catalyst complex is a necessary prerequisite for the carbonylation to proceed.