Breaking the dogma of catalysis: hydrogenation of aldimines with alkaline earth metal catalyst

Industrial scale hydrogenation of organic compounds has been found all over the world, which is very important for the production of polymers, food and medicine As we all know, hydrogenation can only be carried out smoothly if there is catalyst Until about ten years ago, transition metals were the only choice of hydrogenation catalysts, and then many substitutes emerged Recently, a team led by Professor Sjoerd harder of the University of Erlangen Nuremberg (Fau) in Germany and assistant professor Mercedes Alonso of the Free University of Brussels (VUB) in Belgium published an article entitled "image generation with simple alkaline earth metadata" on nature catalysis Alkaline earth elements can be derived as catalysts for imine hydrogenation, which undoubtedly subverts the traditional concept About 100 years ago, chemist Paul Sabatier first realized that amorphous metals can be used as catalysts for hydrogenation of organic substrates By the middle of the 20th century, the rise of organometallic chemistry has promoted the development of transition metal catalysts Soluble transition metal catalysts have been developed to provide higher reactivity In addition, the introduction of ligand molecules combined with metal atoms enhances the selectivity of catalysts, including substrate selectivity and stereoselectivity Despite these advances, the vast majority of industrial catalysts still come from platinum, palladium, rhodium and ruthenium These metals are expensive, rare and toxic, and it costs a lot to remove them from the product The existence of the above problems, together with the increasing environmental problems, urges people to look for alternatives to traditional hydrogenation catalysts One of the strategies is to develop transition metal catalysts with rich reserves and low toxicity, such as iron, cobalt and nickel Figure 1 Four kinds of imine hydrogenation catalysts: a) organic metal hydride; b) Bronsted acid organic catalyst; c) bifunctional catalyst; d) FLP type catalyst source: nature catalyst, DOI: 10.1038/s41929-017-0006-0 In the past decade or so, there have been amazing discoveries in the field of hydrogenation In 2006, stephand et al Found that some molecules containing boron and phosphorus can react reversibly with hydrogen (Science 314, 1124-1126 (2006)) Later, they found that such reactions involving boranes and phosphines were affected by electronic effects and steric hindrances (J am Chem SOC 129, 1880-1881 (2007)) This allows specific boranes and phosphines to activate hydrogen molecules and thus mediate hydrogenation of various types of compounds In 2008, harder's team reported the hydrogenation of olefins with calcium based catalysts (angelw Chem Int EDN 47, 9434-9438 (2008)) These findings show that hydrogenation can also be realized in catalytic systems other than transition metals, which overturns the chemical dogma of more than 100 years The harder   team further expanded the range of alkaline earth metal derivatives that can catalyze hydrogenation The general formula of the new catalyst is m [n (SiMe3) 2] 2, in which m can be magnesium, calcium, strontium or barium These compounds can be easily prepared, and the aldehyde imine hydrogenation involved in them is shown in Fig 2 Thirty reactions were carried out with different reaction conditions and substrates Most of the reactions can achieve 99% conversion in 15 min to 24 h by changing the catalyst equivalent (2.5% - 10%), hydrogen pressure (1-12 bar) and temperature (80-120 ℃) Fig 2 The hydrogenation of aldehydes and imines catalyzed by alkaline earth metals comes from nature catalysis, DOI: 10.1038/s41929-017-0006-0 It is found that the hydrogenation of aldehydes and imines with large volume and weak nucleophilicity of C atom in C = N group is slow On the contrary, the larger the metal atom in the catalyst, the higher the catalytic activity That is to say, the reactivity of magnesium catalyst is the lowest, while that of calcium, strontium and barium catalyst is increasing gradually In other words, the previously reported calcium catalyst is a highly efficient catalyst for the hydrogenation of aldimines, indicating that the activity of the existing calcium catalyst can be optimized by the combination of modified ligands and metal atoms Most of the aldimines involved in catalytic hydrogenation contain phenyl, which is connected to the carbon atom in the imine group The experimental results show that the substrate containing electron acceptor and electron donor can be compatible with this kind of catalytic reaction However, the reaction also has limitations, alkaline earth metal catalyst can not achieve the hydrogenation of ketimine The author also proposed the mechanism of catalytic cycle, as shown in Figure 3 First, the catalyst reacts with hydrogen to generate a transient hydride intermediate, which may be reversible (Fig 3a); then, the aldehyde imine is inserted into the M-H bond of the hydride to generate a diamine intermediate (Fig 3b); the intermediate reacts with hydrogen to release the hydrogenated product amine (Fig 3C), and at the same time regenerates the hydride to continue to participate in the catalytic cycle The proposed mechanism seems simple, but the author points out that the active catalyst has not been identified When the catalyst reacts with hydrogen alone, the hypothetical hydride intermediate is obtained, but the polymerized hydride is also formed Figure 3 Simple diagram of alkaline earth metal catalytic hydrogenation mechanism source: nature, DOI: 10.1038/d41586-017-09006-6 Then, the author calculated and simulated the reaction to further clarify the reaction mechanism The simulation results show that the polymerization process may release energy, indicating that the current uncertainty is caused by the thermodynamic driving force Finally, we use the previously reported calcium hydride complexes as the model of catalytic hydrogenation intermediates, and find that the catalytic way of aldimine and hydrogen is consistent with the assumed catalytic cycle Compared with the industrial reaction catalyzed by transition metal complexes, the new reaction of the harder   team needs more catalysts, and the reaction speed is relatively slow However, these findings expand the range of alkaline earth metals that can be used for catalytic hydrogenation, and increase the possibility that low-cost and low toxicity catalysts can be used in industrial production This work provides further evidence that the doctrine that transition metals must be used for catalytic hydrogenation needs to be eliminated The next step is to find the catalyst with impurity tolerance like industrial reagent Paper link: https://www.nature.com/articles/s41929-017-0006-0 corresponding author: http://harder-research.com/index.php/people/prof https://cris.vub.be/en/persons/mercedes-alonso-giner (db88ca6c-6bbf-4e61-bc9c-bc19a0aeb0ab) HTML sjoerdharder   professor (left) and Mercedes alons assistant professor (right)