Synthesis of Indoles via Electron-Catalyzed Intramolecular C–N Bond Formation

Abstract

A new protocol for the preparation of N-substituted indole-3-carboxylates has been developed. The key C−N bond formation occurs under transition-metal-free conditions employing a t-BuOK/DMF system without special initiators or additives. Across a number of substrates, indoles were afforded in yields higher or comparable to those obtained under transition-metalcatalyzed conditions. While demonstrating high functional group tolerance, new conditions are particularly attractive for manufacturing halogenated indoles that cannot be made in a pure form using other metal-based catalytic methods.

Highly Reactive Cyclic Monoaryl Iodoniums Tuned as Carbene Generators Couple with Nucleophiles under Metal-Free Conditions

“…Starting from 1a and 1a-alike cMAVIs, our structurally diversified coupling products 4 could be transformed into different series of heterocyclic fragments ( Figure 4 ). 4aa-4ag underwent palladium-catalyzed intracellular C-N formation to accomplish the indole ring construction in series 1 compounds (5a-5g) ( Bugaenko et al., 2018 ; Ignatenko et al., 2010 ). Meanwhile, the terminal vinyl double bond in 4aa could be used as an acceptor for halogenation ( Meimetis et al., 2014 ; Song et al., 2013 ).…”

Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018–2021)

“…The more recent catalytic approaches for the efficient synthesis of indole ring have been illustrated in Fig. 1 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 . The catalyst PtCl 4 was explored by Chaisan and co-workers 12 in 2018 to promote the hydroamination of 2-alkylanylaniline for the preparation of 2-substituted indoles.…”

“…In 2018, N -substituted indole-3-carboxylates were prepared in good yields with the help of t -BuOK/DMF system under transition metal free conditions reported by Bugaenko and others 16 . These conditions are mainly suitable for the production of halogenated indoles without any traces of dehalogenation products.…”

Pd-Catalyzed Redox-Neutral C–N Coupling Reaction of Iminoquinones with Electron-Deficient Alkenes without External Oxidants: Access of Tertiary (E)-Enamines and Application to the Synthesis of Indoles and Quinolin-4-ones

“…Enamines are prominent organic intermediates that play a pivotal role in a variety of essential transformations such as acylation, alkylation, and conjugate addition and are useful for the synthesis of chiral compounds such as 2,3-dihydrobenzofurans, 1,3-aminoalcohol, hemiacetal, (−)-paroxetine, and (+)-femoxetine as well as heterocycles such as pyrazoles, isoxazoles, pyridones, pyranones, and pyrimidines . They have been shown to be promising building blocks in various other challenging chemical reactions, to have conspicuous biological activity, and to be important precursors for indole-functionalized drugs . To date, indoles have been recognized as prerogative structures; for instance, 5-hydroxyindole is the structural core in drugs such as serotonin, indomethacin, L-761066, and LY311727, in that they function as neurotransmitters, nonsteroidal anti-inflammatory agents, COX-2 inhibitors, and selective inhibitors of secretory phospholipase s-PLA2, respectively .…”