Nickel‐Catalyzed C−H Bond Functionalization of Azoles and Indoles

Abstract

Direct CÀ H functionalization of privileged and biologically relevant azoles and indoles represents an important chemical transformation in molecular science. Despite significant progress in the palladium-catalyzed regioselective CÀ H functionalization of azoles and indoles, the use of abundant and less expensive nickel catalyst is underdeveloped. In the recent past, the nickel-catalyzed regioselective CÀ H alkylation, arylation, alkenylation and alkynylation of azoles and indoles have been substantially explored, which can be applied to the complex organic molecule synthesis. In this Account, we summarize the developments in nickel-catalyzed regioselective functionalization of azoles and indoles with a considerable focus on the reaction mechanism.

Advancement in the C–H bond alkylation of (hetero)arenes catalyzed by the most abundant transition metal–iron

“…The regioselective C(2)-H and C(3)-H functionalization of indoles is extensively explored using various metal catalysts, whereas the benzenoid C-H functionalization is less investigated. 17,101 The cost-effective 3d metal catalysis, 99,102 particularly iron catalysis, is emerging as an alternative to precious metals due to its low-cost, environmentally benign, and low toxic nature. In the realm of catalysis and viable chemical manufacturing, iron has been mainly demonstrated for the C2 and C3 alkylation of indole derivatives.…”

Recent Advances on Direct Functionalization of Indoles in Aqueous Media

“…Functionalization of indoles by C−C bond formation is one of the most well‐studied areas in the construction of indole derivatives, covering most of the reaction sites in the indole pyrrole moiety and benzene ring part [39,40] . Additionally, the types of catalysis for these reactions are diverse, including catalyst‐free, metal‐catalyzed, [41,42] organocatalyzed, [43] visible light‐mediated, [44] etc. With such a wide range of substrate types and catalytic systems, it is unsurprising that most of them use organic solvents as reaction media due to the poor solubility of most reaction substrates in water and the potential for deactivation and reduced selectivity of many catalysts, especially metal catalysts.…”

Advances in the Iron-Catalyzed Direct Functionalizations of ­Heterocycles

“…Overcoming the challenges associated with the alkylation of indoles, various noble metal catalysts, and low-cost base-metal catalysts were utilized for direct alkylation. 3e 11 Given the high abundance and low toxicity of iron, there has been significant attention paid to use the iron for direct alkylation of indoles and related heteroarenes. In an early example, Itoh showed the C-3 alkylation of free- NH indole with vinyl ketones using Fe(BF 4 ) 2 as a catalyst in acetonitrile (Scheme 1 ).…”

“…The precious 4d metals and 3d base-metal catalysts could be used to achieve regio­selective functionalization of indole. 3a c e 4b 5c 10 This section describes the developments in the sustainable iron-­catalyzed C–H functionalization of indoles, including the scopes and limitations.…”