Three-Component Cascade Synthesis of Carbazoles through [1s,6s] Sigmatropic Shift under Metal-Free Conditions

Abstract

A novel method was developed for the synthesis of substituted carbazoles from commercially available starting materials under metal-free conditions. This strategy involves a [1s,6s] sigmatropic shift step and introduces an electron-withdrawing ester substituent at the C2 position of the carbazole ring. The present protocol afforded the desired carbazole derivatives with good regioselectivity and well functional group tolerance. DFT calculations were carried out to support the reaction pathway.

Recent Advances of Three‐component Reactions of Simple Indoles

“…Under suitable conditions, six‐membered Diels‐Alder intermediates 29.1 were able to undergo the dehydrogenation and aromatization to form carbazole derivatives [38a–e] . This is a good strategy for building polycyclic aromatics.…”

Recent Studies of Bifunctionalization of Simple Indoles

“…Scheme 18 is a brief summary of applications of Diels‐Alder [16a–e] among indoles, ketones and alkenes. The nucleophilic attack of indole C3 to carbonyl group and dehydration afforded dienes as the key intermediates.…”

“…Diels‐Alder reaction occured, followed by a proton shift to yield tetrahydrocarbazoles [16b] . These compounds could even get a further oxidation/ Diels‐Alder [16a] or oxidation/ arylation [16a,c–e] cascade. For example, the Yan group [16a] developed the NH4I‐promoted access to fused and bridged cyclic pyrrolo[3,4‐a]carbazoles.…”

Aerobic Oxidative Functionalization of Indoles

“…In 2019, the same group used methacrylates instead of acrylates to observe a [1 s,6 s] sigmatropic shift step and hence introduce an electron-withdrawing ester substituent at the C2 position of the resultant carbazole ring. [113] For cascade annulations involving indoles under aerobic conditions, Hu et al reported double CÀ H functionalization of indoles via three-component reac-tions for the synthesis of polyfunctional cyclopenta [b] indoles (Scheme 50). [114] The reaction sequence involves a Rh 2 (OAc) 4 -catalyzed multi-component coupling reaction and CuCl 2 -catalyzed aerobic post-cyclization process.…”