Synthesis of indolo[2,1‐a]isoquinolines by CF₃COOH‐induced cyclization

Abstract

Indolo[2,1-a]isoquinoline alkaloids and related compounds have been known to have interesting biological activities, such as antileukemic and antitumor activities. We found that 1-(3,4-dimethoxyphenethyl)indole gave 2,3-dimethoxyindolo [2,1-a]isoquinoline and 1-(3,4-dimethoxyphenylacetyl)indole gave 2,3-dimethoxy-6-oxoindolo[2,1-a]isoquinoline, respectively, by an intramolecular cyclization carried out in boiling trifluoroacetic acid.

Pseudo Four-Component Synthesis of 5,6-Dihydroindolo[2,1-a]isoquinolines

“…The reaction progress was monitored by TLC (Sorbfil, EtOAc/hexane 1/ 1). 5, 6,9,4′:4,5]pyrrolo [2,1-a]isoquinolines 10a−d precipitated out of the reaction mixture.…”

“…Yield 196 mg (62%), yellow solid: mp = 294−295 °C. 9,150.6,148.2,146.8,145.1,136.3,134.6,131.9,130.7 (2C),130.2 (2C),127.9 (2C),127.1,126.5,126.2,119.5,119.0,116.8,116.5,114.9,112.6 (2C),111.5,108.8,91.8,75.7,55.5,55.0,54.1,41.1,28.1 ppm. IR spectrum (KBr) isoquinoline -8,10-dicarbonitrile (6b).…”

“…8 A number of approaches to the synthesis of indolo[2,1a]isoquinoline derivatives have been described in the literature. 9 However, in an effort to improve the complex and multistage process of assembling the indoloisoquinoline skeleton, derivatives of indoles and isoquinolines are commonly utilized as starting compounds. For example, the Miura 10 and Cui 11 groups successfully produced indolo [2,1a]isoquinolines and furo [3,4-c]indolo [2,1-a]isoquinolines, respectively, through rhodium-catalyzed reactions of 2-phenylindoles with alkynes.…”

“…A number of approaches to the synthesis of indolo­[2,1- a ]­isoquinoline derivatives have been described in the literature . However, in an effort to improve the complex and multistage process of assembling the indoloisoquinoline skeleton, derivatives of indoles and isoquinolines are commonly utilized as starting compounds.…”

Synthesis of Indolo[2,1-a]isoquinolines by Nickel-Catalyzed Mizoroki–Heck/Amination Cascade Reaction

“… During the last two decades, indolo­[2,1- a ]­isoquinoline motifs have attracted increasing considerable attention from medicinal and synthetic chemists due to their extensive applications. In general, the synthetic methods have focused on the formation of the fused indole ring and include rhodium-catalyzed oxidative coupling, palladium-catalyzed C–H activation, radical cyclizations, and so forth . However, many of these traditional strategies for the synthesis of indolo­[2,1- a ]­isoquinoline motifs still require the use of expensive catalysts containing metals such as Rh, Pd, etc.…”