Cobalt(Ⅱ)-Catalyzed Direct C–H Amination Of Arenes Assisted By An N,O-Bidentate Directing Group

In this thesis, a variety of benzamide substrates employing 2-aminopyridine 1-oxide moiety as the N,O-bidentate auxiliary group were synthesized. For the first time, inexpensive cobalt salt could be ultilized as the catalyst in the C-H amination of arenes with simple alkylamines. This method could tolerate a broad range of arylamide substrates bearing various functional groups including methoxy, methyl, tert-butyl, phenyl, trifluoromethyl, fluoro, chloro, bromo and even iodo. Additionally, on the basis of reaction results and DFT calculation, a plausible reaction mechanism was proposed. The main research results were shown as follows: 1. Synthesis of benzamide substrates 1 containing 2-aminopyridine 1-oxide moietyBenzamide substrates 1 were obtained by the reaction of the corresponding benzoic acids with 2-Aminopyridine 1-oxide(1.1 equiv.) in CH2Cl2 solvent in the presence of EDCI and DMAP for 12 h(Scheme 1, Yields: 75-92%).2. Cobalt(Ⅱ)-Catalyzed C–H Amination of Arenes with Simple Alkylamines By exploring the template reaction of 2-benzamidopyridine 1-oxide(1a) with morpholine(2a), the optimized reaction condition was obtained as following: Co(OAc)2·4H2O(10 mol%), Na OAc(2.0 equiv.), Ag NO3(2.5 equiv.), KNO3(0.5 equiv.), air, Me CN(0.5 m L), 85 oC(Scheme 2). With this standard condition in hand, the reaction provided the amination yields from 14% to 91% with 34 examples in all.3. Proposed Reaction Process of Cobalt-Catalyzed C-H Amination To probe the reaction course of C-H bond, a series of control experiments were conducted. The lack of KIE(~1.2) was observed in the parallel reaction of 1a and [D5]-1a with 2a, indicating that C-H cleavage was not rate-limiting step(Scheme 3). The addition of radical quencher, 2,2,6,6-tetramethyl-1-piperidinyloxy(TEMPO), 2,6-diisopropyl-4-methylphenol(BHT) or p-benzoquinone(BQ)(1.0 equivalent in each case), totally inhibited the reaction. The electron paramagnetic resonance(EPR) spectrum of the crude reaction mixture clearly showed the existence of a single electron(g = 2.0013). Guided by further density functional theory(DFT) calculations, a plausible mechanism was proposed(Scheme 3).