Liu Qiang research group of Tsinghua University and Lan Yu research group of Chongqing University reveal the ligand effect in manganese catalytic hydrogenation: mechanism research and Application

Catalytic hydrogenation has been widely used in organic synthesis and chemical production, which usually requires the use of precious metal catalysts to promote the smooth occurrence of reactions In view of the demand of sustainable chemical development, the hydrogenation catalyzed by cheap metals has made rapid development in recent years Although manganese is the third most abundant transition metal, manganese catalyzed hydrogenation was not first reported until 2016 At present, the research of manganese catalytic hydrogenation is mainly aimed at the development of new and more inert carbonyl derivatives Among them, the mechanism research is relatively less, especially the structure-activity relationship between the ligand structure and catalytic activity has not been reported It is not difficult to find through literature research that the three tooth PNP and NNP clamp type manganese catalysts are the two most widely used catalysts Among them, a series of PNP type clamp manganese catalysts have been reported to be able to be used for hydrogenation of aldehydes, ketones, imines, nitriles, and ester carbonyl compounds However, NNP type clamp type manganese catalyst can catalyze hydrogenation of more inert carbonyl compounds such as amides, carbonates and urea derivatives (Fig 1a) The above results seem to indicate that NNP type Mn catalyst has higher catalytic hydrogenation activity than PNP type Mn catalyst Figure 1 Manganese catalytic hydrogenation and its ligand effect research and application (photo source: J am Chem SOC.) in order to understand and verify the ligand effect law, Liu Qiang research group of Tsinghua University and Lanyu research group of Chongqing University carried out a detailed mechanism study The results show that NNP type clamped manganese catalyst has stronger electron delivery capacity and smaller steric hindrance than PNP type clamped manganese catalyst, which leads to NNP type clamped manganese catalyst showing higher activity in hydrogenation of a series of inert substrates (Fig 1b) Based on this mechanism, the author also developed the first manganese catalyzed hydrogenation of nitrogen-containing unsaturated heterocyclic compounds (Fig 1b) Among them, NNP type manganese catalyst also showed higher activity Further mechanism study shows that the hydrogenation of quinoline, the model substrate, undergoes a series reaction route of 1,2 hydrogenation isomerization imine hydrogenation, and the same ligand effect above determines the difference of reaction activity of different ligands in the process of 1,2 hydrogenation in the speed determination step (Fig 1b) Therefore, the ligand effect found by the authors shows good universality in the hydrogenation of carbonyl and non carbonyl derivatives catalyzed by manganese Firstly, benzoylaniline (1a) was selected as the model substrate to directly compare the hydrogenation activity of n-np and p-NP clamp type manganese catalysts (Fig 2) The results show that more than 90% of the hydrogenated products can be obtained by using NNP type Mn catalyst [Mn] - 1, but no conversion can be obtained by using PNP type Mn catalyst [Mn] - 2 The results show that NNP type Mn catalyst has higher activity in the hydrogenation of carbonyl derivatives Figure 2 Manganese catalyzed hydrogenation of benzoylaniline (photo source: J am Chem SOC.) the author explains the ligand effect in manganese catalyzed hydrogenation from two aspects of steric resistance and electronic factors The comparison of DFT calculation shows that in the transition state of the key hydrogen transfer reaction, the hydrogen transfer transition state structure of n-np-1 pincers manganese catalyst [Mn] - 1 is more "stretched" due to the introduction of plane structure imidazole ring (Fig 3, left), in which the dihedral angle do − C1 − C2 − C3 is 163.4o, and the distance between N atom on the substrate and H atom on the ligand is 2.66 It is Both of them are larger than the corresponding values of the hydrogen transfer transition state structure based on the pincer manganese catalyst of P NP type (right of Fig 3), which shows that the steric resistance of N NP type ligand structure is smaller, so the repulsion between the substrate and the ligand structure is smaller, which can better stabilize the hydrogen transfer transition state, and the reaction is easier to occur Fig 3 The transition structure of manganese catalyzed hydrogenation of benzoylaniline (photo source: J am Chem SOC.) in addition to the steric resistance factor, the electronic effect also plays an important role in regulating the reactivity of manganese hydrogen The researchers compared the negative hydrogen dissociation energy (HDE) of two pincers, among which, the N NP pincers have smaller negative hydrogen dissociation energy (FIG 4A), which means that the N NP ligands are more electron rich and can better stabilize the manganese cations after the negative hydrogen dissociation In addition, the Millikan charge distribution of negative hydrogen on n-np and p-np-type pincers is − 0.23 and − 0.18, respectively (Fig 4b), which indicates that the more electron rich n-np ligands increase their nucleophilic ability of negative hydrogen Figure 4 Negative hydrogen dissociation energy and Millikan charge analysis (photo source: J am Chem SOC.) in order to further explore the electron donating properties of pincers, the authors synthesized six different structures of amino manganese and tested their c o infrared vibration absorption frequency (Figure 5) For the three kinds of amino manganese containing isopropylphosphine structure units, the test results show that imidazole's electron delivery ability is stronger than pyridine and alkylphosphine (Fig 5a), for the three kinds of amino manganese containing phenylphosphine structure units, the test results show that imidazole's electron delivery ability is stronger than pyridine, and pyridine's electron delivery ability is stronger than arylphosphine (Fig 5b) The results show that the electron delivery capacity of different ligand units is imidazole > pyridine and alkylphosphine > arylphosphine (Fig 5C) In conclusion, compared with PNP type, NNP type clamped manganese catalyst has stronger electron delivery capacity and smaller steric hindrance, which leads to NNP type clamped manganese catalyst showing higher activity in hydrogenation of a series of inert substrates Fig 5 Infrared test results of aminomanganese a tr-ftir with different structures (photo source: J am Chem SOC.) based on this mechanism, the author further considers whether the ligand effect can be applied to hydrogenation of other types of substrates, especially for hydrogenation of non carbonyl derivatives In order to verify this assumption, the researchers used quinoline as the model substrate, and compared the reaction activity of different n-np and p-NP clamp type manganese catalysts in quinoline hydrogenation (Fig 6) The results showed that NNP type Mn catalyst also showed higher activity than PNP type Mn catalyst in the hydrogenation of heterocyclic compounds, and NNP type Mn catalyst was used to realize the high efficiency and high selectivity hydrogenation of 32 different heterocyclic compounds Fig 6 Manganese catalyzed quinoline hydrogenation (photo source: J am Chem SOC.) the author took quinoline hydrogenation as an example, and also carried out a detailed mechanism study The hydrogenation of quinoline, the model substrate, experienced a series reaction route of 1,2 hydrogenation isomerization imine hydrogenation (Fig 7) In the first step, the activation energy of the 1,2 addition reaction determines the difference of the activity between the n-np and p-NP clamp type manganese catalysts Therefore, the ligand effect found by the authors shows good universality in the hydrogenation of carbonyl and non carbonyl derivatives catalyzed by manganese Figure 7 Results of manganese catalyzed quinoline hydrogenation mechanism (photo source: J am Chem SOC.) were published in Journal of the American Chemical Society (DOI: 10.1021 / JACS 9b09038) The authors of this paper are Yujie Wang +, Lei Zhu +, Zhihui Shao, gang Li, Yu Lan *, and Qiang Liu * Tutor introduction: Liu Qiang (http://cbms.chem.tsinghua.edu.cn/liugroup/about.html) Lan Yu (http://hgxy.cqu.edu.cn/szll/ly.htm)