Advances on Nickel-Catalyzed C(sp3)-C(sp3) Bond Formation

Transition metal-catalyzed coupling reactions are powerful synthetic methods for the C-C bond formation. Many coupling reactions such as Heck reaction, Negishi coupling, and Suzuki coupling have been widely applied in the syntheses of pharmaceuticals, functional materials and fine chemicals. In those coupling reactions, a C(sp(2))-C(sp(2)) bond is formed in high efficiency and selectivity. However, in contrast to the C(sp(2))-C(sp(2)) couplings, the C(sp(3))-C(sp(3)) couplings are more difficult and develop late. Because the C(sp 3 )-C(sp(3)) bonds are ubiquitous in organic compound, the C(sp(3))-C(sp(3)) bond formation is the central task of research in organic chemistry. In the past two decades, a great effort has been devoted to the development of cross-coupling reactions between alkyls to construct C(sp(3))-C(sp(3)) bonds and impressive progress has been achieved. Among the transition metal catalysts that have been used in the construction of C(sp(3))-C(sp(3)) bonds, nickel was found to be a preferable one, exhibiting unique activity and selectivity. Nickel catalysts promote the activation of alkyl electrophiles via radical catalytic cycles and inhibit and/or manipulate beta-H elimination reactions. Nickel has several variable valence states and can flexibly participate in tandem reactions and reductive cross-coupling reactions. All these characteristic natures contribute to the success of nickel catalysts in the construction of C(sp(3))-C(sp(3)) bonds. In this review, we will describe the advances on the nickel-catalyzed C(sp(3))-C(sp(3)) bond-forming reactions. The main contents of this review include: the cross-coupling of alkyl electrophiles with organometallic reagents; the coupling involving a C(sp(3))-H bond activation in the presence of directing group; the coupling co-catalyzed by nickel and photocatalyst; the reductive coupling of two alkyl electrophiles; and the additions of nucleophiles or electrophiles to alkenes such as hydroallcylation and difunctionalization of alkenes. The review will focus on the latest developments of nickel-catalyzed alkyl coupling reactions in the past two decades. The mechanisms of each reaction are discussed in detail for understanding the reactions.