Double C-H Activation for the C-C Bond Formation Reactions

Background: Among the numerous bond-forming patterns, C-C bond formation is one of the most useful tools for building molecules for the chemical industry as well as life sciences. Recently, one of the most challenging topics is the study of the direct coupling reactions via multiple C-H bond cleavage/activation processes. A number of excellent reviews on modern C-H direct functionalization have been reported by Bergman, Bercaw, Yu and others in recent years. Among the large number of available methodologies, Pdcatalyzed reactions and hypervalent iodine reagent mediated reactions represent the most popular metal and non-metal involved transformations. However, the comprehensive summary of the comparison of metal and non-metal mediated transformations is still not available. Objective: The review focuses on comparing these two types of reactions (Pd-catalyzed reactions and hypervalent iodine reagent mediated reactions) based on the ways of forming new C-C bonds, as well as the scope and limitations on the demonstration of their synthetic applications. Conclusion: Comparing the Pd-catalyzed strategies and hypervalent iodine reagent mediated methodologies for the direct C-C bond formation from activation of C-H bonds, we clearly noticed that both strategies are powerful tools for directly obtaining the corresponding pruducts. On one hand, the hypervalent iodine reagents mediated reactions are normally under mild conditions and give the molecular diversity without the presence of transition-metal, while the Pd-catalyzed approaches have a broader scope for the wide synthetic applications. On the other hand, unlike Pd-catalyzed C-C bond formation reactions, the study towards hypervalent iodine reagent mediated methodology mainly focused on the stoichiometric amount of hypervalent iodine reagent, while few catalytic reactions have been reported. Meanwhile, hypervalent iodine strategy has been proved to be more efficient in intramolecular medium-ring construction, while there are less successful examples on C(sp(3))-C(sp(3)) bond formation. In summary, we have demonstrated a number of selected approaches for the formation of a new C-C bond under the utilization of Pd-catalyzed reaction conditions or hyperiodine reagents. The direct activations of sp2 or sp3 hybridized C-H bonds are believed to be important strategies for the future molecular design as well as useful chemical entity synthesis.