[Corrigendum] angelw: Professor Li Chaojun and Zeng Huiying of Lanzhou University realized palladium catalyzed C-H functionalization in aqueous phase

In recent years, researchers have realized the regioselective activation of C-H bond (scheme 1a) by using the intermediate of ring metallization formed by guiding group However, the guiding group needs to be introduced in advance and is usually difficult to be removed from the product Although researchers have developed removable or traceless guiding bases to overcome these challenges, they usually need to use stoichiometric guiding bases (scheme 1b) Recently, the researchers formed transient guiding group (scheme1c) by adding reversible guiding group of catalytic amount The "two in one" strategy will be very attractive for the transformation of environmental protection and atomic economy In this strategy, the transient guiding group reacts with C-H bond activation site as a substrate at the same time Recently, Lanzhou University and Professor Li Chaojun have proposed the "two in one" strategy and successfully applied it to palladium catalyzed C-H functionalization in water phase In this kind of reaction, C-H bond of indole or pyridine at C2 position is activated by palladium catalyst, and then cyclized with transient guiding group (imine) to form a new C-C bond, so as to construct a variety of tetrahydro β - carboline frameworks (scheme 1D) with quaternary carbon centers Relevant results were published on angelw Chem Int ed (DOI: 10.1002 / anie 201813391) (source: angelw Chem Int ed.) in the early stage of the study, the author devoted to optimize the C-H functional reaction conditions of tryptamine 7a and cyclopentanone 8A (Table 1) In argon atmosphere, when 5-equivalent sodium formate is used as base and Pd / C is used as catalyst, 9A (entry 1) of spiro ring product can be obtained by reacting 7a and 8A in water at 100 ℃ for 24 hours with 50% yield Inspired by the results, the authors investigated different palladium catalysts The results showed that PD (OH) 2 / C was the best catalyst, and the yield was 80% (entry 6) When the sodium formate was reduced to 3 equivalent and the reaction time was reduced to 6 h, the yield did not change significantly (entries 7-10) When ketone was increased to 3 equivalent, the yield was 93% (entry 11) The control experiment showed that sodium formate and Pd (OH) 2 / C were necessary for the reaction (source: angelw Chem Int ed.) after obtaining the optimal reaction conditions, the author next investigated the range of various ketone substrates (Table 2) Although cyclopentanone can obtain spiro product 9A in an excellent yield (90%), increasing the size of Cyclopentanone will lead to a decrease in the yield of the corresponding product 9b-9c, which may be due to the increase of steric hindrance Heterocyclic ketone or cyclohexanone can react smoothly with tryptamine, and the corresponding spiro product can be obtained in medium yield for 9D - 9h In addition, linear ketone is also a suitable substrate, and the cyclized product 9i - 9K is obtained in good yield Ketoacids can also react well, forming the cyclized product 9l-9m in a short time If the reaction time is prolonged, the intramolecular amine ester exchange reaction will take place further, forming the fused ring compound 10 and the bridge ring compound 11 (source: angelw Chem Int ed.) then, the author investigated the universality of the reaction with various substituted tryptamines as substrates (Table 3) Tryptamine compounds with electron donor or electron acceptor at different positions of benzene ring can obtain the corresponding cyclized product 9N - 9R in good yield The product 9s - 9y can also be obtained from tryptamine substrates with alkyl, ester and amide groups at C1 position of the side chain (source: angelw Chem Int ed.) based on mechanism experiments and related literature, the author proposed a reasonable reaction mechanism (Figure 2) In water, palladium and sodium formate produce HPD II h species The transient guiding group imine A is formed by condensation of tryptamine and cyclopentanone The isolated pair electron coordination of imine forms palladium ring intermediate B, which releases hydrogen at the same time, thus realizing highly selective C-H activation at C2 position Then, at high temperature, the lone pair electron coordination between palladium and imine changes to π - bond intermediate C Then, the polar unsaturated bond with imine is cyclized to form intermediate D Finally, the ligand exchange between intermediate D and sodium formate was carried out to obtain spiro product 9a and regenerate hpdiih species (source: angelw Chem Int ed.) in order to explore the practicability of the "two in one" strategy and further exclude the reaction pathway of Pictet Spengler, the author studied the electron deficient aromatic system which could not be reacted under Pictet Spengler condition (Table 4) It is gratifying that a series of electron deficient aromatic substrates can be successfully cyclized with ketone to form the corresponding product 15A - 15F under slightly changed conditions (source: angelw Chem Int ed.) conclusion: the author realized the C-H functionalization of tryptamine derivatives in aqueous phase by "two in one" strategy The transient guiding group acts as both guiding group and reaction substrate in the reaction Through this strategy, various tetrahydro - β - carboline skeletons with quaternary carbon centers have been synthesized In addition, the strategy can be extended to the electron deficient aromatic system which can not be reacted under Pictet Spengler condition.