Research group of Professor Ke Zhuofeng, Sun Yat sen University: the strategy of non dual functional outer layer mechanism to realize the efficient c-alkylation of ketone and alcohol

The "hydrogen borrowing" reaction has become a very effective synthetic method in synthetic chemistry It provides a new green synthesis method for the formation of C-C bond and C-N bond In order to realize the "hydrogen borrowing" reaction successfully, the inner mechanism strategy based on the double function outer mechanism and metastable ligand has been a hot topic in recent years However, the introduction of bifunctional sites or metastable ligands usually faces some disadvantages, such as difficult synthesis, air sensitivity and high price On the contrary, there are few reports on the strategy of non dual functional outer layer mechanism Recently, the research group of Professor Ke Zhuofeng of Sun Yat sen University has successfully realized the "hydrogen borrowing" c-alkylation of ketone and alcohol (DOI: 10.1021 / ACS Orglett 9b003030) by the combination of experiment and theoretical calculation and the special strategy of non dual functional outer layer mechanism Prof Ke Zhuofeng, professor and doctoral supervisor of School of materials science and engineering, Sun Yat sen University Fifc fellow of Kyoto University, Japan, national fund for studying abroad, was awarded the "one hundred talents plan" of Sun Yat sen University in 2012, and the "one hundred million talents plan" of Guangdong Province for outstanding youth in natural science and "one hundred million project youth of Guangdong special support" in 2015 Research interests mainly focus on the field of bionic bifunctional catalysis Through the combination of theory and experiment, research new strategies, mechanisms and methods of catalytic molecular transformation, carry out rational catalyst precise design, and explore its application in renewable energy and sustainable chemistry More than 80 papers have been published in J am Chem SOC., angel Chem., int ed., chem SCI., ACS Catalyst., org Lett., chem Commin., etc At present, the main research directions are as follows: 1 Theoretical calculation of precise catalyst design; 2 New methods of renewable catalysis and synthesis; 3 Renewable energy, renewable resources and materials Professor Ke Zhuofeng's research achievements: the strategy of non dual functional outer layer mechanism to realize the efficient c-alkylation of ketones and alcohols in synthetic chemistry, "hydrogen borrowing" reaction is a very economic and green synthesis method Because of its advantages such as atomic economy, cheap raw materials, environmental protection of by-products, no need for additional oxidants or reducers, it is a very potential sustainable green catalytic reaction, which has been widely concerned by researchers In recent years, the strategy based on the double function outer layer mechanism and the metastable ligand inner layer mechanism has been the research hotspot in this field However, the introduction of bifunctional sites or metastable arms usually faces the disadvantages of difficult synthesis, air sensitivity and high price On the contrary, there are very few reports based on the strategy of non dual functional outer layer mechanism (Figure 1) Fig 1: design strategy in "hydrogen borrowing" reaction (source: Organic letters) Recently, Professor Ke Zhuofeng's research group successfully realized an outer layer mechanism strategy based on non dual functions to efficiently catalyze the alkylation of ketone and alcohol by combining experimental and theoretical calculation (Fig 2) Figure 2: transition metal catalyzed alkylation of ketones and alcohols (source: Organic letters) The author found that the metal hydrogen of the complex has better hydrogenation performance for a, b-unsatisfied aldehyde ketone intermediates compared with the traditional phosphine containing ligands by DFT theoretical calculation (Figure 3), and has the potential to achieve more efficient hydrogenation "Hydrogen borrowing" reaction Figure 3: DFT theoretical calculation and prediction of hydrogenation of manganese (I) metal intermediate (source: Organic letters) The author optimized the template reaction of Acetophenone and benzyl alcohol by using the bidentate Nitrogen Heterocyclic Carbene manganese (I) complex, and obtained the target product with 91% yield under the optimal condition Compared with other reported bifunctional manganese (I) catalytic systems (125-140 OC, 18-24 h), the non bifunctional outer layer strategy of Nitrogen Heterocyclic Carbene manganese (I) can rapidly complete c-alkylation at 110 OC, 2 h In order to explore the substrate applicability of this method, the author investigated the ketone and alcohol substrates containing various functional groups (Figure 4) Many electron rich and electron deficient acetophenone and benzyl alcohol are suitable substrates, including halogens, ethers, heterocyclic ketones and alcohols, and even O-substituted acetophenone and benzyl alcohol with large steric hindrance Figure 4: after the study of the application scope of ketone and alcohol substrates (source: Organic letters), the author applied the method to the study of friedla ̈ nder cyclization (Figure 5) It was found that the reaction also had good substrate applicability Good yields can be obtained for a variety of acetophenone substrates containing various functional groups Figure 5: Study on the substrate applicability of friedla ̈ nder cyclization (source: Organic letters) Finally, through control experiment and DFT theoretical calculation, the author proposed a non dual function outer layer mechanism (Figure 6) DFT results show that the dehydrogenation of the system can be facilitated by the help of exogenous protons The results provide an important new idea for the design of non noble metal catalysts Figure 6: possible reaction mechanism (source: Organic letters) The research results were recently published on organic letters (DOI: 10.1021 / ACS Orglett 9b003030) Professor Ke Zhuofeng of Sun Yat sen University and Associate Professor Liu Yan of Guangdong University of technology are the corresponding authors The first author of the paper is LAN Xiaobing, Ph.D., and ye Zongren, Ph.D (author: Xiao-Bing Lan, Zongren Ye, Ming Huang, Jiahao Liu, Yan Liu, Zhuofeng Ke）。 The research was supported by the National Natural Science Foundation of China, Guangdong provincial fund for Distinguished Young Scholars, Guangdong special support program, etc.