Multifold C–C Coupling and Unorthodox Cyclization Catalysis for Selective Synthesis of Indolotriarylmethanes, Indolocarbazoles, and Their Analogues: A Control Experiment Study

Abstract

The selective construction of medicinally and synthetically important indole-based unsymmetrical triarylmethanes using indoles and aldehydes is challenging because the significant nucleophilicity of indole leads to C-C coupling with an azafulvene intermediate to build up the alternative bis(indolyl)methane products, which may be useful synthons. A new, straightforward, ligand-free Cu catalytic strategy for easy syntheses of unsymmetrical indolotriarylmethanes and new bisindolylbenzoyl analogues is established through the dual C-C coupling of an assembly of three reaction partners comprising aldehydes, indoles, and arylboronic acids. More importantly, this approach is exploited for multifold C-C coupling cyclization reactions with C-C cleavage using symmetrical bisindolylbenzoylmethanes in the presence of an organic base and aerial molecular oxygen as a stoichiometric oxidant. In contrast to the formation of a simple cyclocondensation product indolocarbazole, it undergoes unprecedented selective pseudo-four-component tandem oxidative cyclization with fragmentation from a 1,3-dicarbonyl compound to produce valuable fused 5,7-dihydroindolo[2,3-b]carbazoles through the functionalization of two indole C(sp)-H and one C(sp)-H bond of the active methylene residue. For a better understanding of the new reactions, we have studied various competition experiments and ESI-MS and 3D Mid-IR-ATR spectral analyses of the ongoing reactions. The predicted DFT transition state model is also in agreement with the experimental results.

Free Radical Triggered Convenient Synthesis of Bis(indolyl)methane with Potassium Peroxodisulfate as Catalyst

“…Among them, indole moiety is one of the most important heterocyclic compounds having excessive π -electron density and a nitrogen atom along with other carbon atoms. [1,2] Indole is the building block of a large number of agrochemicals, natural products, pharmaceuticals, etc. [1][2][3][4][5][6][7][8] Among the various indole based molecules, bis(indolyl)methanes (BIM), is highly attractive because of their wide range of applications in the fields of pharmaceutical and agrochemical industries, material sciences, etc.…”

“…[1,2] Indole is the building block of a large number of agrochemicals, natural products, pharmaceuticals, etc. [1][2][3][4][5][6][7][8] Among the various indole based molecules, bis(indolyl)methanes (BIM), is highly attractive because of their wide range of applications in the fields of pharmaceutical and agrochemical industries, material sciences, etc. [8,12] Bis(indolyl)methane derivatives promote metabolism of estrogen, inducing apoptosis in cancer cell of the human, radical trapping activities, bacterial, fungal, inflammatory, chronic fatigue and tuberculosis treatment, etc.…”

“…In nature, a large number of heterocyclic compounds are widely distributed due to their importance in various life processes. Among them, indole moiety is one of the most important heterocyclic compounds having excessive π ‐electron density and a nitrogen atom along with other carbon atoms . Indole is the building block of a large number of agrochemicals, natural products, pharmaceuticals, etc …”

Direct synthesis of completely unsymmetrical triarylmethanes via Fe(III) salt‐mediated in situ o‐quinone methides process

“…[35][36][37][38][39][40][41][42][43][44][45][46][47] Although several three-component reactions have been reported for the synthesis of unsymmetrical triarylmethanes, the products were often limited to indolotriarylmethanes with moderate yields. [48][49][50][51][52][53][54][55][56][57][58] Therefore, the development of a straightforward method to build the completely unsymmetrical triarylmethanes in one step from readily available starting materials remains elusive. Here, we have established a novel and efficient method for the preparation of unsymmetrical triarylmethanes.…”

A Brønsted‐Acidic Ionic Liquid Gel as an Efficient and Recyclable Heterogeneous Catalyst for the Synthesis of Bis(indolyl)methanes under Solvent‐Free Sonication

“…Indole is an important structural building block frequently found in pharmaceuticals and agrochemicals. [1 – 5] Particularly, bis(indolyl)methanes have exhibited a broad spectrum of biological activities, such as HIV ‐ 1 integrase inhibition, [6 – 8] antimicrobial, antitumor, [10 – 12] antifungal, [13 , 14] and antibacterial …”