RESUMEN
We disclose herein a metal-free cascade reductive Friedel-Crafts alkylation/cyclization of keto acids/esters for the synthesis of tetralones and indanones. Owing to the simple reaction conditions and setup, this protocol features broad substrate generality, facile scalability, and remarkable functional group tolerance, including the synthesis of bioactive molecule sertraline.
RESUMEN
We have developed a straightforward and efficient synthetic protocol to produce 5,6,7,12-tetrahydrobenzo[2,3]azepino[4,5-b]indole and 7,12-dihydro-6H-benzo[2,3]oxepino[4,5-b]indole derivatives under mild conditions. This annulation process involves the intramolecular cyclization of the in situ generated ketimine moiety via the formation of dihydrospiroindolequinoline, which serves as a key intermediate in the reaction pathway. Several control experiments and spectroscopic studies were performed to elucidate the underlying reaction mechanism.
RESUMEN
Herein, we have disclosed pentafluorophenol as an operative catalyst for synthesizing (spirocyclic) tetrahydro-ß-carbolines via the Pictet-Spengler reaction. This straightforward catalytic protocol works under mild conditions resulting indole alkaloids in excellent yield with remarkable functional group tolerance, including late-stage modifications. This transformation demonstrates a practical and adaptable approach to produce a highly effective gram-scale synthesis of the natural alkaloid Komavine and enables the synthesis of the commercial drug Tadalafil.
RESUMEN
A novel and effective Brønsted acid-catalyzed chemoselective synthesis of bis(indolyl)alkanes and 3-alkyl indoles is reported. The selectivity of two significant indole derivatives is attained by allowing the same substrates to go through divergent reaction routes catalyzed by different catalysts. Furthermore, this mild approach is applicable to a wide range of substrates and has high efficacy in large-scale reactions. A plausible mechanism is provided based on the control experiments and spectroscopic studies.
Asunto(s)
Alcanos , Indoles , Alcanos/química , Catálisis , Indoles/química , Óxidos , EstirenosRESUMEN
This work describes a mild and robust double hydroarylation strategy for the synthesis of symmetrical /unsymmetrical diaryl- and triarylmethanes in excellent yields using Lambert salt (0.2-1.0â mol%). Despite the anticipated challenges associated with controlling selective product formation, unsymmetrical diaryl- and triarylmethanes products are obtained unprecedentedly. A highly efficient gram scale reaction has also been reported (TON for symmetrical product=475 and for unsymmetrical product=390). The synthetic utility of the methodology is demonstrated by the preparation of several unexplored diaryl- and triarylmethane-based biologically relevant molecules, such as arundine, vibrindole A, turbomycin B, and certain anti-inflammatory agents. A total synthesis of an anti-breast-cancer agent is also demonstrated. Control experiments, Hammett analysis, HRMS and GC-MS studies reveal the reaction intermediates and reaction mechanism.
Asunto(s)
Neoplasias , Elementos de Transición , Aldehídos , Catálisis , Ácidos de LewisRESUMEN
Herein, a mild metal-free and efficacious route for the synthesis of biologically important 3-aryl oxindole derivatives is described. Using Lambert salt-initiated hydroarylation of isatin, a diverse array of monoarylated products, symmetrical/unsymmetrical double-arylated products, and deoxygenated hydroarylated products could be synthesized from the single starting substrate in good to excellent yields. A preliminary mechanistic study revealed that the reaction proceeds via a monoarylated product followed by a nucleophilic attack by another electron-rich arene nucleophile under mild conditions. The potential of newly synthesized symmetric/unsymmetric 3,3-disubstituted oxindole, 3-substituted 3-hydroxy oxindoles, 3,3-di(indolyl)indolin-2-ones, and α-aryl oxindoles as valuable building blocks is further illustrated.