The activation of ubiquitous C-H bonds has great significance in the field of organic synthesis given that it represents an ideal method for directly producing valuable chemicals from structurally simple compounds. First-row transition metals have recently been recognized as a potential alternative to noble transition metals because of their low cost, unique reactivity profiles, and easy availability. Among these metals, nickel (Ni) catalysts have drawn considerable attention from the scientific community. This review focuses on Ni-catalyzed C-H functionalization reactions of (hetero)arenes, including alkylation, arylation, alkenylation, alkynylation, borylation, and trifluoromethylation by using non-directing group strategies. In addition, mechanistic aspects of Ni-catalyzed C-H functionalization reactions are discussed because this allows possible new insights into catalyst improvement.
Nickel-catalyzed
oxidative C(sp2)–H/C(sp3)–H coupling
of indoles with toluene derivatives is
successfully achieved in the presence of 2-iodobutane as the oxidant.
This method allows the selective C-2 benzylation of indoles with toluene
derivatives over the alkylation with 2-iodobutane and permits the
coupling of diversified indoles via the monochelation assistance.
The reaction proceeded through a single-electron-transfer (SET) process,
wherein both the C–H nickelation of indole and the C–H
activation of toluene derivatives have a significant effect on the
entire reaction rate. The synthetic utility of this nickel-catalyzed
protocol is demonstrated by the facile removal of the directing group
and by the convenient synthesis of the melatonin receptor antagonist
Luzindole derivatives.
Well-defined and efficient POCN-ligated palladium complexes have been developed for the direct C-H bond arylation of azoles with aryl iodides. The phosphinite-amine pincer ligands 1-(R2PO)-C6H4-3-(CH2N(i)Pr2) [(R2)POCN(iPr2)-H; R = (i)Pr (), R = (t)Bu ()] and corresponding palladium complexes {2-(R2PO)-C6H3-6-(CH2N(i)Pr2)}PdCl [((R2)POCN(iPr2))PdCl; R = (i)Pr (), R = (t)Bu ()] were synthesized in good yields. Treatment of palladium complex with KI and AgOAc afforded the complexes ((iPr2)POCN(iPr2))PdI () and ((iPr2)POCN(iPr2))Pd(OAc) (), respectively. Similarly, the reaction of with benzothiazolyl-lithium produces the ((iPr2)POCN(iPr2))Pd(benzothiazolyl) () complex in a quantitative yield. The pincer palladium complex efficiently catalyzes the C-H bond arylation of benzothiazole, substituted-benzoxazoles and 5-aryl oxazoles with diverse aryl iodides in the presence of CuI as a co-catalyst under mild reaction conditions. This represents the first example of a pincer palladium complex being applied for the direct C-H bond arylation of any heterocycle with low catalyst loading. A preliminary mechanistic investigation reveals that palladium nanoparticles are presumably not the catalytically active form of and supports the direct involvement of the catalyst , with complex being a probable key intermediate in the catalytic reaction.
A general nickel-catalyzed method for the alkynylation of heteroarenes through monodentate chelation assistance is described. Many heterocycles, including indoles, pyrroles, imidazoles, and pyrazole, efficiently coupled with (triisopropylsilyl)alkynyl bromide, and synthetically important functional groups, such as halides, ether, nitrile, and nitro, are tolerated. Synthetic applicability of this Ni-catalyzed method is demonstrated by the removal of the triisopropylsilyl group and further functionalization to triazolyl, benzofuranyl, and alkynyl arene derivatives. Preliminary mechanistic investigations of the alkynylation of indole suggest that the reaction proceeds through kinetically relevant C-H activation and follows a two-electron redox pathway. A catalytically relevant Ni species, namely, [(Phen) Ni]NiBr (PheN=1,10-phenanthroline), was isolated and structurally characterized.
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