Study On The Formation Of C-X Bonds Catalyzed By N-Heterocyclic Carbenes

Organosulfur compounds, γ,γ-disubstituted butenolides and amides are very important compounds which are prevalent in natural products, pharmaceuticals and biological and have widespread application in the field of medical chemistry and biochemistry. The formation reactions of C-S, C-C, C-N bonds are the essential for the synthesis of these compounds.N-Heterocyclic Carbebe(NHC) as the organocatalysis have been achieved significant progress in the past decade and catalyzed many typical reactions. But with the further research, the type of reaction catalyzed by N-Heterocyclic Carbene constantly broadened. This paper is mainly base on the NHC-catalyzed the formation of C-S, C-C, C-N bonds and synthetic the α-thioenal, γ,γ-disubstituted butenolides and amides. The main contents include three parts as follow:1.N-Heterocyclic Carbene-catalyzed the formal cross-coupling reaction of α-haloenals with thiols to construct C-S bond. In the presenece of 5 mmol% IMes·HCl, 1.6equiv K2CO3 in dichloromethane, 20 α-thioenals were obtained in 51-90% and good Z-selectivity and 19 α-thioenals are the new compounds. Finally, a proposed mechanism was presented and we detected the intermediate of bisulfenylated aldehyde and it can be transformed into the desired product under the optimization conditions.2. NHC-catalyzed the direct vinylogous Michael of γ-substituted butenolides to construct C-C bond. In the preseneceof 5-20 mmol% IPr catalyst, 30 kinds of γ,γ-disubstituted butenolides were obtained in 38-99% yield and excellent diastereoselectivity(up to 99:1) and the anti-adduct as the major product. Finally, a proposed mechanism shows that the NHC plays a role of Br?nsted base and first NHC activate the butenolides by the hydrogen bond, then undergo conjugate addition to give the desired product.3.NHC-catalyzed the amidation of vinyl erters with aromatic amines to construct C-N bond. In the presence of 6 mmol% IMes·HCl and 5 mmol% tBu OK, 28 amides compounds were obtained in 51-100% yield. Two proposed mechanism were also given and the reaction mechanism were further studied by the 1H NMR and 13 C NMR experiments. Besides, the reaction can be scaled-up easily while maintaining the high yield and there are prospects for industrial application.In summary, based on NHC as the organocatalysis,we developed the most efficient approaches to construct the C-S bond, γ,γ-disubstituted butenolides and amides with the advantage of mild reaction conditions and atom economy. The application of NHC were also expanded.