Ir(I)-Catalyzed C–H Bond Alkylation of C2-Position of Indole with Alkenes: Selective Synthesis of Linear or Branched 2-Alkylindoles

Abstract

A cationic iridium-catalyzed C2-alkylation of N-substituted indole derivatives with various alkenes has been developed, which selectively gives linear or branched 2-alkylindoles in high to excellent selectivity. This protocol relies on the use of the carbonyl group on the nitrogen atom of indole as a directing group: a linear product was predominant when an acetyl group was used as a directing group, and a branched product was predominant with a benzoyl group.

Regioselective Catalytic Alkylation of N-Heterocycles in Continuous Flow

“…In order to achieve regioselectivity on indole derivates and related heterocycles alkylation, methods have been widely investigated [12][13][14][15][16][17]. The nucleophilic nature of the carbon atom in the 3-position [18] makes the indole susceptible towards direct alkylation reactions.…”

Rh(III)-Catalyzed, Highly Selectively Direct C–H Alkylation of Indoles with Diazo Compounds

“…This reaction relied on a norbornene-mediated cascade process. Shortly after, Shibata developed a cationic iridium-catalyzed C2-alkylation for efficient synthesis of C2-alkyl substituted indoles with various alkenes [22]. Later, Glorius described a Rh(III)-catalyzed C-H alkylation of indoles with allylic alcohols with an excess amount of Cu(OAc) 2 as an oxidant, while stoichiometric amounts of salt waste are generated as a byproduct [23,24].…”

Palladium-Catalyzed Regioselective 2-Carbethoxyethylation of 1H– Indoles By C-H Activation: One-Step Synthesis of Ethyl 2-(1H-Indol-2-Yl) Acetates

“…Owing to the development of the transition-metal catalyzed C-H activation chemistry, methods for regioselective direct C2/C3-alkenylation [27][28][29][30][31][32][33], alkynylation [34][35][36][37][38][39][40][41], cyano [42,43] and arylation [44][45][46][47][48][49][50][51][52] of indole nucleus have been well developed to date. However, regioselective C2-alkylation of indole is more challenging.…”