Copper-Catalyzed N−H Functionalizations of NH-Sulfoximines for C−N Bond Formation

Recently, N−H functionalizations of NH-sulfoximines have arouse considerable attention because of interesting biological activities of the resulting products. In this thesis we presented three types of N−H functionalizations of NH-sulfoximines for the construction of C(sp3)−N bonds and C(sp2)−N bonds by copper catalysis. First, a copper-catalyzed A3-coupling of sulfoximines, aldehydes, and alkynes was achieved, and provided a variety of N-propargylsulfoximines in good yields. This C(sp3)−N bond formation allowed for good compatibility of functional groups of these three substrates. Mechanistically, a sulfoximinium derived from sulfoximines and aldehydes was suggested as the key intermediate involved in the A3-coupling. Then, we developed an efficient method for the synthesis of ketoacyl sulfoximines starting from sulfoximines and aryl methyl ketones. In the presence of copper catalysts under the oxygen atmosphere, a wide range of aryl methyl ketones were suitable to couple with various sulfoximines giving the desired products in good yields. This copper-catalyzed oxidative amidation involved the cleavage of three C(sp3)−H bonds and one N−H bond, and the formation of one new C(sp2)−N bond.The last project described a copper-catalyzed N−arylation of NH-sulfoximines with nonacidic arenes with an assistance of an aminoquinoline directing group. Oxygen from the air atmosphere served as terminal oxidant, and was efficient to promote the dual C(sp2)−H/N−H activation in the presence of copper catalysis. The arylation underwent a cross-dehydrogenative coupling process, affording sulfoximidoyl-containing benzoic acid derivatives in moderate to excellent yields ranging from 46%-92%