Iodine mediated intramolecular C2-amidative cyclization of indoles: a facile access to indole fused tetracycles

Abstract

A novel and metal-free I2-mediated intramolecular C2 amidation of indoles under mild reaction conditions is developed. This methodology affords various indole fused tetracyclic compounds, such as benzo[4,5]imidazo[1,2-a]indoles by intramolecular C2 amidation of N-aryl substituted indoles. This C2 sulfonamidative cyclization also offers convenient access to indolo[2,3-b]indoles and dihydroindolo[2,3-b]quinoline from C3 aryl substituted indoles in good to excellent yields. Indolo[2,3-b]quinolines are also synthesized by the domino cyclization-detosylation-aromatization reaction sequence.

I+/TBHP Catalysis For Tandem Oxidative Cyclization To Indolo[2,3‐b]quinolines

“…Based on our recent findings regarding the tandem oxidative dearomative [11] cyclization of homotryptamines, [12] we report here the hypoiodite‐catalyzed [13,14] chemoselective tandem oxidative cyclization of indole derivatives 2 tethered to aniline sulfonamides to give indolo[2,3‐ b ]quinolin‐5‐ium sulfonates 3 under mild conditions using catalytic amount of tetrabutylammonium iodide and TBHP as an oxidant at room temperature (Scheme 1d). Although, similar to previous iodine‐mediated intramolecular coupling reactions under basic conditions, [9e] our catalytic oxidative coupling proceeded under nearly neutral conditions via a similar intermediate dihydroindolo[2,3‐ b ]‐quinoline 4 , but to give the products 3 as sulfonate salts, which could be easily isolated in analytically pure form via only a simple filtration of the crude reaction mixture. In addition, both N ‐unsubstituted and N ‐Me indole derivatives 2 could be used under our catalytic conditions to give the corresponding indolo[2,3‐ b ]quinolin‐5‐ium salts 3 in good to high yields.…”

“…In addition, concentrated HCl was required to achieve the second step and tosyl chloride was generated as a side product of detosylation. On the other hand, Sekar and colleagues reported an intramolecular tandem cyclization of indole derivatives tethered to aniline sulfonamide followed by detosylation and aromatization to give the corresponding indolo[2,3‐ b ]quinolines (Scheme 1c) [9e] . However, similar to the intermolecular coupling reaction shown in Scheme 1b, [9c] the substrate scope of this intramolecular reaction was also limited to N ‐alkyl substituted indoles.…”

“…However, similar to the intermolecular coupling reaction shown in Scheme 1b, [9c] the substrate scope of this intramolecular reaction was also limited to N ‐alkyl substituted indoles. In addition, both the inter‐ and intramolecular coupling methods required a stoichiometric amount of molecular iodine in the presence of cesium carbonate under heating conditions [9c,e] …”

Unified Strategy to Access 6H‐Benzofuro[2,3‐b]indoles and 5,6‐Dihydroindolo[2,3‐b]indoles via UV Light‐Mediated Diradical Cyclization

“…In contrast, only a few methods for the construction of 6 H ‐ benzofuro[2,3‐ b ]indoles and 5,6‐dihydroindolo[2,3‐ b ]indoles have been reported. The major synthetic approaches to 5,6‐dihydroindolo[2,3‐ b ]indoles include two classes: (i) Pd‐mediated C−I/C−H or oxidative C−H/C−H coupling reaction (Scheme , path (a)), (ii) electrophilic amination of arene C−H bond, Cadogan cyclization, and iodine‐mediated cyclization (path b) . As for 6 H ‐ benzofuro[2,3‐ b ]indoles, there are only two synthetic routes via copper‐mediated coupling reaction or oxidative cycloamination reaction in literature.…”

Metal-free C–H sulfonamidation of pyrroles by visible light photoredox catalysis

“…15 Another approach is the sulfonamidation of indoles by stoichiometric amounts of iodine. [16][17][18] In 2008 Moeller et al developed an intramolecular sulfonamidation of alkenes by electrochemical oxidation of electron-rich double bonds and subsequent C-N bond formation with a sulfonamide anion [19][20][21][22] and in 2013 Nicewicz et al published the catalytic anti-Markovnikov intramolecular hydroamination following a similar concept. They oxidized the alkene with the organic photocatalyst 9-mesityl-10-methylacridinium 23 followed by an intramolecular reaction with the sulfonamide.…”