Some Investigations On Cross-Coupling Reaction Involving Metal Carbene

Metal carbene is a kind of important organic synthetic intermediate. Because of its unique and rich reactivity, this area attracted considerable attention of chemists in the last several decades. Chromium(O) Fischer carbene is an important member in the field of metal carbene. It is stable and could be easily isolated. The synthesis and reactivity of these metal complexes received indepth exploration and investigation. Apart from this relatively stable chromium(O) Fischer carbene complexes, some metal carbene precursors such as a-diazocarbonyl compounds or conjugated enynones, could also give metal carbene species in the presence of transition metals. The metal carbene species thus generated were usually active and could not be easily separated. However, it can be served as intermediate in catalytic reactions and experience a series of classical carbene transformations.In recent years, with the rapid development of cross-coupling reactions in organic synthesis, metal carbene process and cross-coupling reactions have been merged together. Such integration provides a new opportunity for further development of carbene chemistry. In this novel type of cross-coupling reactions, the carbene sources or precursors are generally used as reaction substrates. These substrates could afford highly active metal carbene intermediates in the presence of transition metals. The metal carbene species thus generated could be coupled with other components in the reaction system.In the research of my doctoral thesis, we firstly developed a cross-coupling reaction of chromium(O) Fischer carbene complexes with N-tosylhydrazones. In this transformation, the relatively stable chromium(O) Fischer carbene complexes were selected as carbene source. This reaction could deliver enol ether by taking advantage of electrophilicity of chromium(O) Fischer carbene complexes and.N-tosylhydrazones were served as nucleophiles. The enol ether could be converted into arylketone by hydrolysis, which provides an alternative approach for diaryl-ethonanes. Secondly, we developed a cross-coupling reaction of benzoxazoles with chromium(O) Fischer carbene complexes. Similarly, the chromium(O) Fischer carbene complexes were also used as electrophiles, while benzoxazole derivatives acted as nucleophiles in this transformation. This study achieved C-H bond functionalization of benzoxazoles under catalyst-free conditions.Next, we explored some related reactions on active metal carbene species, which was regard as vital intermediates in catalytic reactions. As we all know, the combination of palladium carbene and cross-coupling reactions was relatively early and it was gradually developed into maturity. Firstly, we developed a palladium-catalyzed three component reaction of N-tosylhydrazone, norbornene and aryl halide. This transformation provides an efficient method for double functionalization of norbornene. Secondly, we realized C-H bond activations of N-phenoxyacetamides with N-tosylhydrazones or α-diazocarbonyl compounds, in which the latter were used as carbene precursors. This reaction not only introduced N-tosylhydrazones as adequate component in rhodium-catalyzed C-H activations, but also provided a novel and alternative method for ortho-alkenyl phenols.In addition to a-diazocarbonyl compounds and N-tosylhydrazones, conjugated enynones have also been recognized as new entries to metal carbene through the activation of alkyne moiety. Hence, we developed a Cu(I)-catalyzed cross-coupling reaction of conjugated enynones with terminal alkynes. In this study, we have expanded the carbene cross-coupling reactions with migratory insertion process from palladium to copper by employing conjugated enynones as carbene precursors. Meanwhile, we can obtain a series of fury 1-substituted allenes. After this investigation, we developed a copper-catalyzed three component reaction of conjugated enynones, terminal alkynes and allyl halides. Allyl halides were introduced as electrophile in this reaction. This study gives us a deep understanding of migratory insertion process in carbene cross-coupling reactions. In addition, this reaction could provide an alternative route for synthesis of allyl-and furan-substituted allenes.