Synthesis of functionalized indoles via cascade benzannulation strategies: a decade's overview

Abstract

Indoles are one of the most prominent aromatic heterocycles in the organic chemistry space. Due to their widespread presence in various natural products, alkaloids, drugs, approved medicines, etc. synthesis and...

“Back‐to‐Front” Indole and Carbazole Synthesis from N,N‐Bis‐(2‐bromoallyl)amines by Combining Carbolithiation Reactions with Gold‐Catalysis

“…In order to synthesize carbazole derivatives 17 through a double benzannulation process, 3,4bis(alkynol)pyrroles 16 were treated with catalytic amounts of NaAuCl 4 • 2H 2 O (Table 4). Starting substrates bearing a methyl group as R 2 substituent or a hydrogen atom as R 3 group efficiently underwent the expected double cyclization affording symmetrically functionalized 1,3,4,5,6,8,9-substituted carbazoles 17 in good yields (entries 1-4, 6-7, 9-13). However, bisalkynols 16 possessing the propargylic group R 2 bigger than methyl and the alkyne substituent R 3 different from hydrogen, such as 16 ba and 16 da, did Scheme 2.…”

“…This underdeveloped strategy, the benzannulation on the pyrrole, has important advantages for the regioselective functionalization of C4-7 positions. [5] In this area, transition metal-catalyzed annulations, both intramolecular [6] or intermolecular, [7] are the most studied processes, although some metal catalyst-free cyclizations have also been reported (Scheme 1a). [8] In contrast, the benzannulation of properly designed (indolyl)butynols is a well-established methodology for accessing carbazoles from functionalized indoles ("indole-tocarbazole" approach), [9] mainly under transition metal-catalysis.…”

“…Surprisingly, fewer strategies are known for generating the indole core from functionalized pyrroles (“back‐to‐front” approach). This underdeveloped strategy, the benzannulation on the pyrrole, has important advantages for the regioselective functionalization of C4‐7 positions [5] . In this area, transition metal‐catalyzed annulations, both intramolecular [6] or intermolecular, [7] are the most studied processes, although some metal catalyst‐free cyclizations have also been reported (Scheme 1a) [8] .…”

DDQ/Fe(NO3)3-Catalyzed Aerobic Synthesis of 3-Acyl Indoles and an In Silico Study for the Binding Affinity of N-Tosyl-3-acyl Indoles toward RdRp against SARS-CoV-2

“…By virtue of their ubiquitous nature and broad-spectrum appearance in natural and synthetic bioactive compounds and pharmaceutical ingredients, nitrogen heterocycles form an important class of compounds . Providing more emphasis, indoles and their 3-substituted derivatives are always in the center of research because of their widespread applications in pharmaceuticals as potential drug candidates and in the discovery and development of novel functional materials. , In particular, synthesis of 3-acyl indoles has drawn the immense attention of organic synthetic chemists because of their relevance in natural products and pharmaceutical entities and their capability of binding with many biological receptors to show potential anti-tumor, antiviral, and anti-carcinogenic activity (Figure ), and so forth . Moreover, these 3-acylated indoles are versatile key intermediates involved in various functional group transformations to afford valuable simple to complex organic heterocyclic scaffolds. , Therefore, the synthesis of 3-acyl indoles is still of great interest and in the foci of research.…”

Montmorillonite K10 catalyzed facile synthesis of N-substituted indoles from primary amines and Morita–Baylis–Hillman acetate of cyclohexenone

“…In general, these methods can be broadly classified into three categories: (a) the construction of the pyrrole ring from functionalized benzene, exemplified by a number of transition metal-catalyzed couplings 2 and some classic named reactions including Fischer indole synthesis, Bischler indole synthesis, Sundberg indole synthesis, etc. ; 3 (b) cascade benzannulation from pyrroles, being recently reviewed by Maji and coworkers; 4 and (c) the simultaneous building of both rings of the indole such as Nenitzescu indole synthesis and a few elegant cascade reactions, in which cyclohexanone derivatives are generally involved as either a starting material or an intermediate (Scheme 1a). 5 Although there is a plethora of aforementioned methods at our disposal, the synthesis of simple N -arylindoles relies on transition metal-catalyzed N -arylation of indoles in the presence of an expensive ligand and a stoichiometric amount of base (Scheme 1b).…”