Nickel-Catalyzed C-H Direct Amination Of Benzoxazoles With Secondary Amines

The sp2C-N bond reaction is of great interest in organic synthesis. Traditionally methods include nucleophilic substitution, the Cu-catalyzed Ullmann C-N couplings, the Pd-catalyzed Buchwald-Hartwig reaction.2-aminooxazoles are widely employed in biological, pharmaceutical and material sciences. Thus, the synthesis of2-aminooxazoles has reached more and more attention in recent years. While, for the above methods, they often require pre-installation of reactive functional groups (e.g., aryl iodides, bromides, chlorides, triflates and sulfonates) and high temperature as well as the use of expensive ligands(for Ullmann and Buchwald-Hartwig reaction). To further improve the efficiency, an immense effort has been made to develop efficient strategies for the construction of C-N bond. Doubtless, C-H functional is most efficient and atom-economic protocol, also as the future direction of organic synthetic chemistry.In recent years, the synthetic methods of2-aminooxazoles by C-H activation/C-N bond formation have been reported in the literature. They can be divided into three groups:a) Cu-catalyzed synthesis of2-aminooxazoles under alkaline condition, b) acid-promoted transition metal-catalyzed C-H activation/C-N construction of oxazoles, c) free-metal catalyzed C-H direct amination reaction.In this paper, we employed the coupling reaction of benzoxazole and dibutylamine as a model reaction to optimize the catalysts, oxidants, additives, solvents, temperature and other conditions. Finally, the best result was obtained by using5mol%Ni(OAc)2·4H2O as catalyst,3equiv TBHP as oxidant,1.2equiv propionic acid as additives, acetonitrile as solvent, at70℃for12h. and explored the substrate extension experiments. A variety of substituted benzoxazol-2-amines were synthesized in moderated to good yield. This reaction system is good tolerance of functional groups, non-sensitive to water and dioxygen.In this paper, an efficient nickel-catalyzed C-H functionalization approach providing regioselective formation of C-N bonds through C-H direct amination of benzoxazoles has been developed.