C−H Functionalization of Indoles by 3d Transition‐Metal Catalysis

Abstract

Over the past decade, the use of 3d transition metal for the regioselective C−H bond functionalization of indoles has significantly increased. Particularly, advances in manganese, iron, cobalt, nickel and copper catalysis have demonstrated the selective C(2)−H and C(3)−H arylation, alkenylation, alkynylation and alkylation to a greater extent. Similarly, the C−O and C−N bond‐forming reactions are manifested via direct C−H bond activation by these earth‐abundant metals. The emergence of 3d metals in selective functionalization of the biologically relevant indoles and related heteroarenes would make this protocol more attractive for practical applications. Herein, we provide a brief overview of 3d transition metal‐catalyzed (mostly Mn, Fe, Co, Ni and Cu) C−H functionalization of indoles and related heteroarenes.

Controlling selectivity in N-heterocycle directed borylation of indoles

“…To date this area has been dominated by sixmembered heterocycle based directing groups and thus C2 functionalisation. 17…”

Recent Advances in Metal‐Catalyzed Functionalization of Indoles

“…The proposed mechanism involves a single‐electron‐transfer in the Ni(I)/(III) cycle with the C−Cl activation as the proposed rate‐limiting step. Overall, the Ni(I)‐catalyzed C2−H functionalization reactions developed by the Punji group expanded the potential of nickel catalysis in expanding the toolbox of indole transformations using 3d transition metals [40] …”

Crystal structure and Hirshfeld analysis of diethyl (2E,2′E)-3,3′-[1-(8-phenylisoquinolin-1-yl)-1H-indole-2,7-diyl]diacrylate

“…Methods for the synthesis of functionalized indoles have therefore attracted a lot of attention over the past few decades. Among them, transition-metal-catalysed direct C-H activation of the indole framework itself has emerged as a fascinating avenue to afford functionalized indole derivatives on account of its atom economy and simplified procedure (Sandtorv, 2015;Liu, Zhao& Wu, 2017;Jagtap & Punji, 2020). On the other hand, because of the much higher reactivity of the 3-position than the 2-position and in turn than the sites in the six-membered ring (Joule et al, 2000;Fanton et al, 2010), studies on the synthesis of 2,7-disubstituted indole derivatives have scarcely been reported.…”