Acid‐Catalyzed Four‐Component Tandem Double Cyclization: Access to Dihydroindolizino[8,7‐b]indoles

Abstract

The novel one pot four‐component reaction for the construction of dihydroindolizino[8,7‐b]indoles and their derivatives have been developed from ninhydrine, tryptamine, dimetylene acetylene dicarboxylate and aliphatic alcohol. This reaction produces to go through via Pictet‐Spengler cyclization reaction and construction of C−C and C−N bond readily achieved under transition metal free condition. Meanwhile, advantageous of tandem double cyclization are not only reducing reaction steps but also waste production.

Pictet–Spengler-Based Multicomponent Domino Reactions to Construct Polyheterocycles

“…In 2019, the group of Kumbhare reported a novel one-pot four-component cyclization reaction for constructing dihydroindolizino[8,7- b ]indoles 167 from ninhydrin 163 , tryptamine 164 , dimetylene acetylene dicarboxylates 165 , and aliphatic alcohols 166 in the presence of TFA ( Scheme 37 ). 104 In this reaction, the tandem Pictet–Spengler cyclization reaction and construction of C–C and C–N bonds could be produced under transition metal-free conditions at 120°C for 14 hours, finally providing the desired fused-indole derivatives in good yields.…”

Recent applications of ninhydrin in multicomponent reactions

“…Various anilines containing electron donating and withdrawing groups successfully responded under mild conditions. Mechanistically, the NaOHpromoted reaction might proceed via deprotonation of CHCl 3 , 125 The reaction proceeded via Pictet-Spengler, Michael addition and the nucleophilic addition reaction, leading to the formation of C-C and C-N bonds in the MeCN medium. Notably, the heterocyclic motif was achieved through a double tandem cyclisation in the presence of a CF 3 COOH catalyst.…”