Practical Synthesis of Chromeno[2,3‐b]indole Skeleton via an Aldehyde Group Insertion/Aromatization Strategy

Abstract

The synthesis of chromeno[2,3-b]indole from simple starting materials remains a demanding process. Herein, 2-bromoindole undergoes nucleophilic attack from salicylaldehyde, followed by intramolecular insertion of an aldehyde group and aromatization to generate the desired chromeno[2,3-b]indoles. Moreover, various functional groups were tolerated and a gram-scale synthesis of the product could be achieved under the optimized condition.

Synthesis of Dihydrochromeno[2,3-b]indoles via an Fe(OTf)3-Catalyzed Cascade Reaction

“…Yield: 168 mg (71%) yellow liquid (purification by flash column chromatography: petroleum ether/ethyl acetate (15:1)); 1 H NMR (400 MHz, CDCl 3 ) δ 7.63 (s, 1H), 7.34 (dd, J = 8. 5,5.4 Hz,2H),2H),2H),1H),5.93 (s,1H). 13 2-((3,5-Dimethylphenyl)(hydroxy)methyl)phenol (2v).…”

“…The synthesis of chromeno­[2,3- b ]­indoles through intramolecular cyclization of the 3-(2-hydroxybenzyl)-indoles has also been reported; however, precursors with complex structures could be prepared for these methods. In 2017, Liu et al designed a simple and efficient route to synthesize chromeno­[2,3- b ]­indoles from 2-bromoindole and salicylaldehyde via a palladium-catalyzed nucleophilic attack/aldehyde group insertion/aromatization strategy (Scheme a) . Subsequently, they developed another cross-cyclization between salicylaldehydes and indoles for the preparation of chromeno­[2,3- b ]­indole derivatives through the use of elemental sulfur as the promoter and oxidant (Scheme b) .…”

“…In 2017, Liu et al designed a simple and efficient route to synthesize chromeno [2,3-b]indoles from 2-bromoindole and salicylaldehyde via a palladium-catalyzed nucleophilic attack/aldehyde group insertion/aromatization strategy (Scheme 1a). 5 Subsequently, they developed another cross-cyclization between salicylaldehydes and indoles for the preparation of chromeno- [2,3-b]indole derivatives through the use of elemental sulfur as the promoter and oxidant (Scheme 1b). 6 Despite such progress, few methods for the direct synthesis of dihydrochromeno [2,3-b]indole, especially multisubstituted dihydrochromeno [2,3-b]indoles, are disclosed.…”

FeCl3-Promoted Annulation of 2-Haloindoles: Switchable Synthesis of Spirooxindole-chromeno[2,3-b]indoles and Spirooxindole-chromeno[3,2-b]indoles

“…2-Haloindoles are versatile building blocks bearing interesting reactivity and have attracted much attention recently . The introduction of a halo group in the C2-position of the indole ring might alter the reaction pathway of 2,3-indoles.…”

Expedient Synthesis of Indolo[2,3-b]quinolines, Chromeno[2,3-b]indoles, and 3-Alkenyl-oxindoles from 3,3′-Diindolylmethanes and Evaluation of Their Antibiotic Activity against Methicillin-Resistant Staphylococcus aureus

“… 21 Recently, palladium-catalyzed conditions were employed in a cascade reaction between 2-bromoindole and salicylaldehyde. 22 Owing to their limited synthetic approaches, the biological evaluation of these molecules is limited to in vitro antiproliferative activity. 21a Our present method can afford chromeno[2,3- b ]indole under mild conditions with a high yield.…”