Palladium‐Catalyzed Intermolecular Alkenylation of Indoles by Solvent‐Controlled Regioselective CH Functionalization

Abstract

Either the C2‐ or the C3‐substituted product can be obtained with the same palladium(II) catalyst in an oxidative intermolecular alkenylation of indoles. A variety of conditions can be used for derivatization at the 3‐position; however, the presence of acetic acid is required for the C2‐selective process (see scheme). Further elaboration of the products by a similar CH functionalization process leads to the bisalkenylated indoles selectively.

Direct transition metal-catalyzed functionalization of heteroaromatic compounds

“…It was speculated that strongly coordinating solvents such as DMSO or acetonitrile disfavor the migration, thus leading to C-3-regioselectivity, while weakly coordinating solvents, such as 1,4-dioxane, in conjunction with AcOH, facilitate the migration affording the products of C-2 substitution. 102 Further, Gaunt disclosed a method for C-2 and C-3 regioselective intermolecular C-H alkenylation and annulation of pyrroles 198 and 199 (Scheme 69). 103 Notably, the regiochemistry in this mild and high-yielding aerobic protocol can be completely controlled via sterically and electronically tuned N-protecting groups to obtain either C-2 or C-3 functionalized products 199 and 200 selectively.…”

Hg(OTf)2-catalyzed direct vinylation of tryptamines and versatile applications for tandem reactions

“…4 The first approach involves an oxidative addition, which usually takes place at the electron-rich C3 position of indoles and thereby yields a C3-vinylated product. 5 In most cases, catalytic functionalization of C-H at the C2 position poses a difficult problem and often requires a directing group at the N1 or C3 positions, entailing high temperature conditions (Scheme 1c). 6 The other approach employs a metal activator of alkynes, generating electrophilic metal complexes and subsequent hydroarylation reactions.…”

Three different approaches to C-H bond functionalization in the synthesis of antitumor alkaloids rhazinilam, rhazinal and rhazinicine

“…To complete the synthesis a third important step consisted in the formation of the 9-membered lactam (Scheme 8). In previous works, they developed an efficient catalytic system to control the regioselectivity of the alkenylation of indoles 10 and pyrroles. 9 It was…”