66866-10-2Relevant academic research and scientific papers
Cascade alkenyl amination/heck reaction promoted by a bifunctional palladium catalyst: A novel one-pot synthesis of indoles from o-haloanilines and alkenyl halides
Barluenga, Jose,Fernandez, M. Alejandro,Aznar, Fernando,Valdes, Carlos
, p. 2276 - 2283 (2005)
A novel approach for the synthesis of the important indole ring is described. Indoles are obtained from o-bromoanilines and alkenyl halides in a Pd-catalyzed cascade process that involves an alkenyl amination followed by an intramolecular Heck reaction. The overall process represents the first example of the participation of alkenyl amination reactions in Pd-catalyzed cascade reactions. Initially, the relative reactivity of aryl and alkenyl bromides and chlorides towards Pd-catalyzed amination was investigated. Competition experiments were carried out in the presence of primary and secondary amines, and these revealed the reactivity order alkenyl bromides > aryl bromides > alkenyl chlorides > aryl chlorides, as well as very high chemoselectivity; the more reactive halide was always favored. Thereafter, optimized reaction conditions for the sequential alkenyl amination/Heck cyclization to give indoles were investigated with the model reaction of o-bromoaniline with a-bromostyrene. An extensive screening of ligands, bases, and reaction conditions revealed that the [Pd2(dba)3]/ DavePhos, NaOtBu, toluene combination at 100°C were the optimized reaction conditions to carry out the cascade process (dba = dibenzylideneacetone, DavePhos = 2-dicyclohexylphosphino-2'-N,N-dimethylaminobiphenyl). The reaction proceeds with aryl, alkyl, and functionalized substitutents in both starting reactants. The cyclization was also studied with N-substituted o-bromoanilines (which would give rise to N-substituted indoles); however, in this case, indole formation occurred only with 1-substituted-2-bromoalkenes. Finally, the application of this methodology to 0-chloroanilines required further optimization. Although the catalyst based on DavePhos failed to promote the cascade process, a catalytic combination based on [Pd2(dba)3]/X-Phos promoted the formation of the indole ring also from the less reactive chloroanilines.
Copper-Catalyzed Direct Arylation of Indoles and Related (Hetero)arenes: A Ligandless and Solvent-free Approach
Pandey, Dilip K.,Shabade, Anand B.,Punji, Benudhar
, p. 2534 - 2540 (2020/05/06)
A ligandless and solvent-free copper-catalyzed method for the regioselective C?H bond arylation of indoles and related heteroarenes is reported. The use of CuCl efficiently catalyzes the direct coupling of diverse heteroarenes with aryl iodides via chelation-assistance. This reaction could tolerate sensitive and structurally diverse functionalities, including halides, ethers, thioethers, amines, indolyl, pyrrolyl and carbazolyl groups. The directing group, 2-pyridinyl can be smoothly removed to generate C-2 arylated free-NH indoles, and the arylated indoles can further be functionalized into Tryptamine derivatives. Preliminary mechanistic study revealed a radical pathway for the arylation reaction. (Figure presented.).
2-Phenylindole derivatives as anticancer agents: synthesis and screening against murine melanoma, human lung and breast cancer cell lines
Gaikwad, Ruchi,Bobde, Yamini,Ganesh, Routholla,Patel, Tarun,Rathore, Anju,Ghosh, Balaram,Das, Kalpataru,Gayen, Shovanlal
, p. 2258 - 2269 (2019/06/27)
Indole derivatives have attractive anticancer properties and may be a future hope for better anticancer drug(s) of low toxicity and high potency. In this paper, syntheses of 2-phenylindole derivatives have been described via Fischer indole synthesis through a one-pot solvent-free method. The synthesized compounds were screened for anticancer potential in vitro against murine melanoma (B16F10), human lung cancer (A549), and human breast cancer (MDA-MB-231) cell lines. The results highlighted that 2-phenylindole derivatives are also promising anticancer agents in case of melanoma and lung cancer along with the breast cancer. Molecular docking analyses with possible targets for melanoma (NEDD4-1) and lung cancer (EGFR) were also performed to understand specific interactions of 2-phenylindole derivatives with the amino acid residues of the receptors.
Regioselective Synthesis of 2-Arylindoles via Palladium-Catalyzed Cyclization of Phenylglyoxal and 2-Anilinoacetophenones with Anilines
Benitez-Medina, G. Eliad,Ortiz-Soto, Sofía,Cabrera, Armando,Amézquita-Valencia, Manuel
, p. 3763 - 3770 (2019/06/24)
A versatile route has been developed for the synthesis of 2-arylindoles using a Pd-catalyzed tandem process. Under reductive conditions, different 2-arylindoles were synthesized from phenylglyoxal and aniline. This synthetic methodology involves a tandem reaction of four steps with high regioselectivity. Alternatively, 2-anilinoacetophenones intermediates also can be using to give access to the corresponding 2-arylindoles.
Oxygenophilic Lewis Acid Promoted Synthesis of 2-Arylindoles from Anilines and Cyanoepoxides in Alcohol
Xu, Chuangchuang,Xu, Jiaxi
, p. 14733 - 14742 (2018/11/27)
A convenient synthetic method to indoles from anilines and cyanoepoxides was developed under the catalysis of BF3·OEt2 or AlCl3 in alcohols. The reaction involves a tandem reaction of the regiospecific ring-opening of cyanoepoxides with anilines, elimination of cyanide, intramolecular aromatic electrophilic substitution, and water elimination. The Lewis acid generated protic acid is an efficient catalyst. The method features readily accessible starting materials, wide substrate scope, transition-metal-free environment, and regiospecificity in the ring-opening of cyanoepoxides.
Palladium-Catalyzed C2?H Arylation of Unprotected (N?H)-Indoles “On Water” Using Primary Diamantyl Phosphine Oxides as a Class of Primary Phosphine Oxide Ligands
Moncea, Oana,Poinsot, Didier,Fokin, Andrey A.,Schreiner, Peter R.,Hierso, Jean-Cyrille
, p. 2915 - 2922 (2018/05/14)
We present the Pd-catalyzed arylation of (N?H)-indoles with functionalized haloarenes “on water” using hitherto untested primary diamantyl phosphine oxides (PPO) as ligands. Remarkable C2?H arylation selectivity was achieved by employing functionalized iodoarenes and N-unprotected indoles. We provide evidence that the in situ generated oxide of (9-hydroxydiamant-4-yl)phosphine L1 is key for the reaction efficiency by comparing a set of diamantane-based compounds structurally related to L1. Our results demonstrate the power of the new PPO ligands for the C?H functionalization of unprotected (N?H)-heterocycles.
Through-Space 1,4-Palladium Migration and 1,2-Aryl Shift: Direct Access to Dibenzo[a,c]carbazoles through a Triple C-H Functionalization Cascade
Bhunia, Samir Kumar,Polley, Arghya,Natarajan, Ramalingam,Jana, Ranjan
supporting information, p. 16786 - 16791 (2015/11/16)
A palladium-catalyzed expeditious synthesis of dibenzofused carbazoles from readily available 2-arylindoles and diaryliodonium salts is reported. Interestingly, after the electrophilic C3 palladation of indole, an unexpected "through-space" 1,4-palladium migration to the 2-aryl moiety, by remote C-H bond activation followed by C-H arylation with diaryliodonium salt, and an unprecedented 1,2-aryl shift take place. Finally, an intramolecular cross-dehydrogenative coupling (CDC) at the C2 position affords dibenzo[a,c]carbazoles in high yields. Remarkably, the present migratory annulation occurs through three C-H bond activation one C-C bond cleavage, and the simultaneous construction of three new C-C bonds in a single operation.
Well-defined NHC-Pd complex-mediated intermolecular direct annulations for synthesis of functionalized indoles (NHC = N-hetero-cyclic carbene)
Jin, Zhong,Guo, Su-Xian,Qiu, Ling-Ling,Wu, Gui-Ping,Fang, Jian-Xin
experimental part, p. 502 - 507 (2012/05/04)
As alternatives to the common tertiary phosphine/Pd systems, well-defined N-heterocyclic carbene-Pd complexes have been proven to be highly efficient precatalysts for intermolecular direct annalution of o-haloanilines and ketones at lower catalyst loadings. A highly efficient and practical protocol for synthesis of functionalized indoles was developed using (IPr)Pd(acac)Cl as catalyst. Both o-bromoanilines and o-chloroanilines gave rise to efficient coupling under the reaction conditions. Related to acyclic ones, cyclic ketones coupled more effectively with o-haloanilines. With [Pd(IPr)2] as catalyst, the base-sensitive groups including OH and CO2H groups could be tolerated. Copyright
Antimitotic activities of 2-phenylindole-3-carbaldehydes in human breast cancer cells
Kaufmann, Doris,Pojarova, Michaela,Vogel, Susanne,Liebl, Renate,Gastpar, Robert,Gross, Dietmar,Nishino, Tsuyuki,Pfaller, Tobias,von Angerer, Erwin
, p. 5122 - 5136 (2008/03/27)
Small molecules such as indoles are attractive as inhibitors of tubulin polymerization. Thus a number of 2-phenylindole-3-carbaldehydes with lipophilic substituents in both aromatic rings was synthesized and evaluated for antitumor activity in MDA-MB 231
Microwave-assisted, solvent-free Bischler indole synthesis
Sridharan, Vellaisamy,Perumal, Subbu,Avenda?o, Carmen,Menéndez, J. Carlos
, p. 91 - 95 (2007/10/03)
The solid-state reaction between anilines and phenacyl bromides in the presence of an equimolecular amount of sodium bicarbonate gives N-phenacylanilines. Microwave irradiation of mixtures of these compounds with anilinium bromides at 540 W for 45-60 s provides a mild, general, and environmentally friendly method for the synthesis of 2-arylindoles in 50-56% overall yields. A one-pot variation of the method, involving irradiation of 2:1 mixtures of anilines and phenacyl bromides, was also developed, allowing a simplified experimental procedure and leading to improved yields (52-75%). Georg Thieme Verlag Stuttgart.
