JACS: selective n − n cross coupling of carbazole and diarylamine catalyzed by Cu under aerobic condition

N − n bonds are widely found in natural products, drugs and organic functional materials The classical n − n bond construction methods mainly include the diazotization of aniline with sodium nitrite and Br ø nsted Acid, as well as the reaction using n − chloride or n − electrophilic reagent In addition, the n − n coupling reaction of O 2 oxidation also provides a more green synthesis way for the construction of n − n bond Among them, the intermolecular N-N coupling reactions involving carbazole have been reported, but such reactions often require stoichiometric oxidants, such as KMnO 4, Ag 2O or dichromate In 2014, Phil S Baran synthesized the natural product dixiamycin B by self coupling reaction of electrochemical oxidation of carbazole (J am Chem SOC 2014, 136, 5571) (source: J am Chem SOC.) recently, Professor Shannon S Stahl of University of Wisconsin Madison and his collaborators reported for the first time a Cu catalyzed dimerization and cross coupling reaction of carbazole and diarylamine The mechanism study shows that the formation of tetraarylhydrazine is advantageous in kinetics, but because of the reversibility of the reaction, the fracture of n − n bond eventually leads to the formation of cross coupling products with thermodynamic stability (j.am Chem SOC., 2018, 140, 9074 Doi: 10.1021 / JACS 8b05245) Firstly, the coupling reaction conditions of n − n bond were screened by using 3,6 − di (tert butyl) carbazole 1A as model substrate (Table 1) The results showed that copper (II) salt could not catalyze the reaction (entry 1, 2) With 20 mol% CuBr · DMS as catalyst and 40 mol% DMAP as ligand, the reaction can proceed smoothly, and bicarbazole 2A (entry 10) can be obtained in 72% yield Further reduce the amount of CuBr · DMS to 10 mol%, DMAP to 20 mol%, and the yield of the target product can be increased to 78% (entry13) (source: J am Chem SOC.) then, the author studied the substrate applicability of the dimerization of carbazole and diarylamine (Table 2) The dimerization of carbazole and diarylamine with electron donor or electron acceptor groups in benzene ring can take place In general, the dimerization yield of diarylamine is higher than that of carbazole, and the reaction can be carried out at room temperature Diarylamine 1K can realize self coupling reaction in gram scale In addition, asymmetric diarylamine 1q can also dimerize, but the reaction temperature needs to be raised to 60 ℃ (source: J am Chem SOC.) due to the lack of n − n cross coupling reaction, and the reported methods usually require a large amount of one of the substrates Therefore, the cross coupling reaction between carbazole 1a and diarylamine 1p was attempted When the dosage of the two is 1:1, the coupling product 3A can be obtained in 72% yield, and 10% of the dimer can be generated respectively; when 1a is slightly excessive (1A: 1p = 1.5:1), the yield can be increased to 86% (source: J am Chem SOC.) the author further explored the substrate range of n − n cross coupling reaction (Table 3) Carbazoles with large steric hindrance tert butyl or halogen in benzene ring can cross couple with symmetrical or asymmetric diarylamines, and the cross coupling products can be obtained in medium to good yield, and the reaction can also be enlarged to the gram scale (3b) (source: J am Chem SOC.) in order to clarify the source of cross coupling products, the author analyzed the reaction process by 1H NMR It can be seen from Figure 2 that diarylamine 1p is consumed rapidly at the beginning of the reaction to form tetraarylhydrazine 2p, the concentration of which increases rapidly at first, and then decreases gradually with the formation of cross coupling product 3a This phenomenon shows that the formation of n − n bond in 2p is reversible under the reaction conditions Because the n − n bond of 2p is very weak, its homolysis can produce amino radicals which can cross couple with carbazole The irreversible formation of the thermodynamically stable cross coupling product 3A consumes 2p In addition, the control experiment showed that the n − n bond cleavage in 2p was not promoted by copper (source: J am Chem SOC.) conclusion: Professor Shannon S Stahl of the University of Wisconsin Madison has developed the dimerization and cross coupling reaction of carbazole and diarylamine catalyzed by copper under aerobic conditions for the first time The selectivity of the cross coupling reaction of carbazole and diarylamine comes from the reversible cleavage of N-N bond in the intermediate of tetraarylhydrazine, and the reaction finally produces the carbazole diarylamine product with stable thermodynamics.