A nickel-catalyzed direct C-2 alkylation of indoles through monodentate-chelation assistance has been described. This reaction proceeds via an unusual strategy by the use of a well-designed and defined (quinolinyl)­amido–nickel catalyst, [{κN,κN,κN-Et2NCH2C­(O)­(μ-N)­C9H6N}­Ni­(OAc)], providing a solution to the limitations associated with bidentate-chelate auxiliaries. The method allows coupling of indoles with various unactivated primary and secondary alkyl halides with ample substrate scope. This uniquely strategized alkylation proceeded through crucial C–H activation and via an alkyl radical intermediate. The reaction by this approach represents a rare example of Ni-catalyzed monodentate-chelate-assisted C–H functionalization.

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.

Alkylation represents an important organic transformation in molecular science to develop privileged alkylated arenes and heteroarenes. Especially, the direct C−H bond alkylation using unactivated alkyl halides is a straightforward and attractive approach from both the step-economy and chemoselectivity perspectives. Substantial progress has been made in the direct alkylation using primary, secondary, and tertiary alkyl halides along with the methylation and fluoroalkylation. This Review broadly summarizes the transition-metal-catalyzed alkylations of C−H bonds on various arenes and heteroarenes with unactivated alkyl halides until October 2020. On the basis of the substrates utilized for alkylation, the Review is divided into two major sections: alkylation of arenes and alkylation of heteroarenes.