Synthesis of carbazole compounds by C-H amination of angelw

C-N bonds exist widely in chemical molecules, so the construction of C-N bonds has always been one of the hotspots in organic chemistry Nitrogen guest chemistry has a long history of research, which has a unique advantage in the formation of C-N bond In the past ten years, gold catalyzed transformation of nitrogen to guest has shown unique advantages in the synthesis of heterocycles In this regard, ye, Hashimi, Liu and gagosz have made outstanding contributions In addition, the C-H insertion reaction can also take place to form C-N bond, which is similar to the C-H insertion reaction of carbene Therefore, the nitrogen guest compound is an important synthon in the process of constructing N-containing molecules However, transition metals, expensive ligands, high temperature or strong UV irradiation are often needed to form the intermediate, which is not conducive to the development of green chemistry So far, there are few reports on the conditions of moderate nitrogenation without transition metal catalysis Carbazole and its corresponding heterocyclic compounds are widely found in natural products (Figure 1), such as carprofen, furostifoline, atanisatin, glycoborine, siamenol and clausine families Effective construction of carbazole parent ring is of great significance to improve the molecular drug resistance In addition, polymers with carbazole have important applications in photosensitizers and organic photovoltaic devices (source: angelw Chem Int ed.) therefore, the development of simple methods for the synthesis of carbazole compounds has attracted great attention Among them, the main synthesis methods include: 1) the construction of intermolecular benzene ring; 2) the intermolecular cyclization of unsaturated system; 3) the intermolecular coupling reaction catalyzed by PD; 4) the intramolecular oxidation C-H amination reaction catalyzed by transition metal; 5) the intramolecular aryl nitrogen guest C-H insertion reaction Among these methods, direct C-H insertion of carbene is a more attractive one Chemists often use 2-azido-diaryl as the precursor of nitrogen guest, and use ultraviolet light, laser, high temperature or metal catalyst to excite to produce nitrogen guest intermediate However, these methods all have the risk of explosion, which limits their further application Recently, A Stephen K Hashmi group of Heidelberg University, Germany, reported a new intermolecular C-H amination method to synthesize carbazole compounds The reaction uses thioimine as the substrate, and the conditions are mild and simple Relevant research results were published in angelw Chem Int ed (DOI: 10.1002 / anie 202000146) Firstly, the author used the thioimine compound 2A as the template substrate to optimize the conditions (Table 1) Through the optimization of the reaction conditions such as catalyst, light intensity, etc., the author finally determined the optimal conditions for the reaction: THF as the solvent, reaction under the light conditions at room temperature, the final yield can be 99% to get the target product (source: angelw Chem Int ed.) after determining the optimal reaction conditions, the author then expanded the substrate range of the reaction (Table 2) First of all, the ortho aryl substituent can be obtained in high yield CL, methyl, tert butyl, phenyl and other groups are all compatible with the reaction conditions For the substituent of AR 2, the mixture can be obtained in the ratio of 1:1 In addition, the reaction conditions are also compatible with the halogen substituted thioimines In addition to carbazole compounds, 8 h-thiophene [2,3-b] indole, γ - carboline and other structures can also be synthesized by this method (source: angelw Chem Int ed.) then, the author studied the orthoolefin substituted substrates (scheme1) under the same conditions Fortunately, these substrates can obtain corresponding indoles in medium yield Then, the reaction was amplified and the synthesis of clausine C and clausine n (scheme 2) was realized by using this method (source: angelw Chem Int ed.) (source: angelw Chem Int ed.) finally, the author compared the efficiency of this method and Rh catalytic method with the same substrate, and found that the reaction time of this method is faster and the efficiency is higher; through the deuterium generation experiment (KIE), the speed limit steps of these two methods are the same Summary: A Stephen K Hashmi group developed a new method of C-H amination by using aryl thiamine as the source of nitrogen Compared with the previous method, this condition is more mild, simple, applicable more widely, and there is no potential danger of explosion, which provides a new simple synthesis method for carbazole compounds.