Copper-Catalyzed Or Mediated Reactions On Sp~3-sp~3 Carbon-Carbon Bonds

The construction of carbon-carbon bonds is the core content in organic synthetic chemistry and builds the basis for the synthesis of biologically active molecules. In recent decades, transition-metal catalyzed carbon-carbon bonds formation has emerged as an indispensable tool in modern organic synthesis. Compared with the dominant way which generally involves the coupling of organometallic reagents with organic halides or pseudohalides, driect coupling of two different organic halides or pseudohalides shows practical advantages, such as simplifying reaction steps, avoiding the prior preparation and handling of stoichiometric, usually air-and moisture-sensitive organometallic reagents. On the other hand, transition-metal-mediated C-H functionalization have been developed to one of the most versatile and powerful tool for carbon-carbon bonds formation. This method enables the direct functionalization of ubiquitous C-H bonds by avoiding the usual prefunctionalization steps in traditional cross-coupling reactions. Due to the abundant and hypotoxic nature of the copper catalysts, copper-catalyzed/mediated C-H functionalization has attracted tremendous research interest in recent decades.In the beginning, we gave a concise review of the latest developments of transition metal catalyzed reductive cross-coupling reactions include Co, Pd, Fe and Ni-catalyzed reductive aryl-alkyl or alkyl-alkyl couplings. It is worth noting that present methods disfavored the using of readily available alkyl pseudohalides. And these reactions are usually effective for the aryl-alkyl couplings, but the direct cross-coupling between two alkyl halides is often plagued with the homo-coupling of each alkyl halide reactant. It is still urgent to develop new catalyst systems to improve the scope of reductive couplings. Interestingly, copper, which proved to be an efficient catalyst in coupling reactions involved alkyl halides or pseudohalides, was seldom used in these transformations. Additionally, we also summarized the recent development of copper-catalyzed/mediated C-H functionalization. However, most of these reports are limited to the functionalization of C(sp2)-H bonds or activated allylic or benzylic C(sp3}-H bonds. Much fewer efforts were taken to the functionalization of unactivated C(sp3)-H bonds with copper salts.Next, we reported the first Cu-catalyzed direct cross-coupling reaction between non-activated alkyl pseudohalides with alkyl and aryl bromides. The new method undergoes a mechanism concerning rapid in-situ Grignard reagent formation followed by copper-catalyzed SN2 substitution. Cross-coupling between aryl-alkyl, alkyl-alkyl especially two tertiary alkyl carbons can all be achieved. This method can also be used for the synthesis of 2,3-dihydrobenzofuran and hexahydrobenzopyran derivatives.Finally we reported, for the first time, that copper can promote the unprecedented oxidative demethylation of propionamides with the 8-amidoquinoline-derivied bidentate auxiliary. This novel strategy enables the direct cleavage of the saturated C-C bonds at the a-methyl positions of propionamides with excellent regioselectivity. Further mechanistic studies indicated that a mechanism of initial C(sp3)-H activation followed by oxidative demethylation was involved in this new reaction. It is provides a straightforward way to the functionalization of propionamide derivatives, which are important structural moieties in natural products and medicals.