Catalytic metal-free ketone hydrogenation: a computational experiment

A computational study has been carried out to examine if the metal-free catalyst (1) designed for imine hydrogenation is able to hydrogenate ketones, using the cyclohexanone (3) and its derivatives (4-6) as ketone models. The catalytic cycle includes two major steps: hydrogen activation and hydrogen transfer. The concerted pathway in the hydrogen transfer step is preferred over the stepwise pathway. The two separated steps for hydrogen activation and hydrogen transfer can benefit the hydrogen addition to the substrates (e.g., ketones) which do not have strong Lewis base centres, because the substrates need not to be involved in the hydrogen activation. In general, the larger the steric effect of the substrate is, the less severe the side reactions become, and the more difficultly the desired reaction occurs. The energetic results show that the hydrogenations of 3-5 are kinetically and thermodynamically feasible under ambient conditions, but the hydrogenation of 6 is less energetically favourable. Therefore, it is important to establish a proper balance between promoting the desired reaction and meanwhile avoiding the undesired reactions. The issue of the resting state, caused by forming stable alkoxide complexes like in the ketone hydrogenation catalyzed by the metal-ligand bifunctional catalysts, is also discussed.