RESUMEN
The exploration of remote functionalization of indoles is impeded by the inherently dominant reactivity intrinsic to the pyrrole moiety. Herein, we delineate a novel strategy facilitated by Lewis acid mediation, enabling the remote C-H functionalization, which culminates in the synthesis of an array of selectively functionalized indole derivatives, encompassing 3-trifluoroacetyl and 5-benzoyl motifs, utilizing trifluoroacetic anhydride and various acyl chlorides. Notably, the protocol exhibits versatility, as epitomized by the extension of C5-acylation to alkylation and sulfonation reactions. This methodology is distinguished by its exemplary regio- and chemo-selectivity, extensive substrate scope, commendable tolerance to a diverse array of functional groups, and the employment of comparatively mild reaction conditions.
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An organoselenium-catalyzed C2,3-diarylation of unprotected N-H indoles with electron-rich aromatics has been developed. This one-pot multicomponent tandem cross-dehydrogenation coupling reaction allows for the incorporation of two different aromatic groups to indoles. More importantly, this approach offers significant advantages, including a high atom and step economy, eliminating the need for prepreparation of the reaction substrates, streamlining the synthetic process and enhancing its practicality. Overall, this organoselenium-catalyzed C2,3-diarylation reaction presents an efficient and versatile strategy for the functionalization of indole derivatives.
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Regiodivergent transition-metal-catalyzed oxidative C5- and ortho-alkynylation of 2-arylthiazoles have been demonstrated. Namely, Pd(II)-catalysis selectively generated C5-alkynylated products from the reaction of 2-arylthiazoles and terminal alkynes. In contrast, Ru(II)-catalysis exclusively provided ortho-alkynylated products from the same substrates. This protocol features a wide substrate scope, good functional group tolerance, high atom-economy, and exclusive regioselectivity. The alkynylated products can be readily converted into highly valuable synthons, which hold potential for applications in the fields of medicinal chemistry and materials science.
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Electrochemical carbon dioxide reduction (ECO2RR) shows great potential to create high-value carbon-based chemicals, while designing advanced catalysts at the atomic level remains challenging. The ECO2RR performance is largely dependent on the catalyst microelectronic structure that can be effectively modulated through surface defect engineering. Here, we provide an atmosphere-assisted low-temperature calcination strategy to prepare a series of single-atomic Cu/ceria catalysts with varied oxygen vacancy concentrations for robust electrolytic reduction of CO2 to methane. The obtained Cu/ceria catalyst under H2 environment (Cu/ceria-H2) exhibits a methane Faraday efficiency (FECH4) of 70.03% with a turnover frequency (TOFCH4) of 9946.7 h-1 at an industrial-scale current density of 150 mA cm-2 in a flow cell. Detailed studies indicate the copious oxygen vacancies in the Cu/ceria-H2 are conducive to regulating the surface microelectronic structure with stabilized Cu+ active center. Furthermore, density functional theory calculations and operando ATR-SEIRAS demonstrate that the Cu/ceria-H2 can markedly enhance the activation of CO2, facilitate the adsorption of pivotal intermediates *COOH and *CO, thus ultimately enabling the high selectivity for CH4 production. This study presents deep insights into designing effective electrocatalysts for CO2 to CH4 conversion by controlling the surface microstructure via the reaction atmosphere.
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A cross-coupling reaction via the dehydrogenative route over heterogeneous solid atomic catalysts offers practical solutions toward an economical and sustainable elaboration of simple organic substrates. The current utilization of this technology is, however, hampered by limited molecular definition of many solid catalysts. Here, we report the development of Cu-M dual-atom catalysts (where M = Co, Ni, Cu, and Zn) supported on a hierarchical USY zeolite to mediate efficient dehydrogenative cross-coupling of unprotected phenols with amine partners. Over 80% isolated yields have been attained over Cu-Co-USY, which shows much superior reactivity when compared with our Cu1 and other Cu-M analogues. This amination reaction has hence involved simple and non-forceful reaction condition requirements. The superior reactivity can be attributed to (1) the specifically designed bimetallic Cu-Co active sites within the micropore for "co-adsorption-co-activation" of the reaction substrates and (2) the facile intracrystalline (meso/micropore) diffusion of the heterocyclic organic substrates. This study offers critical insights into the engineering of next-generation solid atomic catalysts with complex reaction steps.
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A metal-free one-pot oxidative cross-dehydrogenation coupling reaction for the formation of C-N/C-C bonds at the C2,3-positions of indoles with azoles and quinoxalinones has been developed. The proposed method has several notable features, including metal-free catalysis, the use of N-H free indoles as substrates, ease of operation, mild reaction conditions, and compatibility with a wide range of substrates.
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Series of (3-phenylisoxazol-5-yl)methanimine derivatives were synthesized, and evaluated for anti-hepatitis B virus (HBV) activity inâ vitro. Half of them more effectively inhibited HBsAg than 3TC, and more favor to inhibit secretion of HBeAg than to HBsAg. Part of the compounds with significant inhibition on HBeAg were also effectively inhibit replication of HBV DNA. Compound (E)-3-(4-fluorophenyl)-5-((2-phenylhydrazineylidene)methyl)isoxazole inhibited excellently HBeAg with IC50 in 0.65â µM (3TC(Lamivudine) in 189.90â µM), inhibited HBV DNA in 20.52â µM (3TC in 26.23â µM). Structures of compounds were determined by NMR and HRMS methods, and chlorination on phenyl ring of phenylisoxazol-5-yl was confirmed by X-ray diffraction analysis, and the structure-activity relationships (SARs) of the derivatives was discussed. This work provided a new class of potent non-nucleoside anti-HBV agents.
Asunto(s)
Virus de la Hepatitis B , Herpesvirus Cercopitecino 1 , Virus de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B , Antivirales/química , Herpesvirus Cercopitecino 1/genética , Antígenos e de la Hepatitis B/farmacología , ADN Viral/genética , ADN Viral/farmacología , Replicación ViralRESUMEN
An efficient copper-iodine cocatalyzed intermolecular C-H aminocyanation of indoles with a broad substrate scope has been developed for the first time. This method enables highly step-economic access to 2-amino-3-cyanoindoles in moderate to good yields and provides a complementary strategy for the regioselective difunctionalization of carbonâcarbon double bonds of interest in organic synthesis and related areas. Mechanistic studies suggest that these transformations are initiated by iodine-mediated C2-H amination with azoles, followed by copper-catalyzed C3-H cyanation with ethyl cyanoformate.
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Indoles , Yodo , Azoles/química , Catálisis , Cobre/química , Indoles/química , Yoduros , Yodo/químicaRESUMEN
A copper-mediated 2,3-difunctionalization of indoles to afford 3-halogenated 2,3'-biindoles is described herein. The protocol uses readily available feedstocks and a naturally abundant copper catalyst system, which allows the regioselective formation of C-C and C-X (X = Cl & Br) bonds in one single operation. Here the copper metal salt serves not only as a catalyst but also as a reactant to provide the source of halogen. This operationally simple procedure avoids the utilization of environmentally unfriendly reagents and displays good functional group compatibility. Noteworthily, the introduction of halogen into molecules would offer great potential for further chemical transformations.
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Herein, we report direct synthesis of 1-N-vinyl-1,2,3-triazoles via silver-mediated three-component cycloaddition reaction of phenylacetylenes, trimethylsilylazide, and 1,3-dicarbonyl compounds. The synthetic protocol proceeds with operational simplicity, good substrate and functional group compatibility, and easily available feedstocks, and without the need for pre-installation of vinylazide precursors, and offers a practical method for the efficient elaboration of triazole derivatives.
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A directing-group-free strategy for oxidative regioselective aminochalcogenation of indolines with amines and dichalconides is presented. This strategy combines tandem coupling sequences and oxidative dehydrogenation methods in a multi-component reaction, enabling the fast construction of a series of C2,3- or C2,5-aminochalcogenated indole derivatives. Moreover, the application of this synthetic approach is demonstrated through the late-stage modification of pharmaceuticals and the derivatization of the products, highlighting its potential and significance.
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We report an innovative synthetic strategy for the generation of polysubstituted indoles from indolines, aryldiazonium salts, and azoles. The methodology encompasses an electrophilic substitution reaction affording C5-indoline intermediates which undergo an iodine-mediated oxidative transformation coupled with C-H functionalization to yield the indole derivatives.
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We have disclosed silver(I)-induced switching of regioselectivity in rhodium-catalyzed C-H alkynylation of indole derivatives with the help of a pivaloyl directing group by tuning C-H metalation modes. The judicious choice of AgOAc, Ag2O, and Ag2CO3 affords an array of C2-alkynylated indoles, C4-alkynylated indoles, and C2,C4-dialkynylated indoles, respectively. The synthetic utility of the alkyne fragment is demonstrated by derivatization into valuable indole-based compounds.
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Two complementary regiodivergent C-H alkynylations of 2-arylthiazoles are reported. When RuII catalysis is employed, an aryl ortho-alkynylation process is favored. The alkynylated products are gained in good yields. With the use of PdII catalysis, a thiazole C5-alkynylation process is developed, allowing for the construction of C5-alkynylated products. This strategy not only expands the methods for the functionalization of 2-arylthiazoles, but also provides new opportunities for the rapid assembly of complex molecular structures, which may have great potential in organic synthesis, medicinal chemistry, and materials science.
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A one-pot strategy for iron-catalyzed C2,3-H arylphosphorylation of electron-deficient quinoxalines with phosphines and aryl compounds is reported. The proposed method features the use of non-noble metal catalysts, the capacity of utilizing multiple aryl compounds as substrates, the simultaneous formation of C-P and C-C bonds in one pot, the simplicity of its operation, the mildness of the reaction conditions, and its compatibility with a wide range of substrates. Moreover, it offers a practical route for direct access to 2-aryl-3-phosphino N-heteroarenes, a class of potential cyclometalated C^N and N^P bidentate ligands that are difficult to prepare with existing C(sp2)-H functionalization methods.
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Based on the inhibitory effect of CA-4 analogues and indoles on tubulin polymerization, we designed and synthesized a series of N-((1-methyl-1H-indol-3-yl)methyl)-2-(1H-pyrazol-1-yl or triazolyl)-N-(3,4,5-trimethoxyphenyl)acetamides. All the synthesized compounds were evaluated for their in vitro antiproliferative activities against HeLa, MCF-7 and HT-29 cancer cell lines, and some of the target compounds demonstrated effective activities towards the three tumour cell lines. Among them, compound 7d exhibited the most potent activities against HeLa (IC50 = 0.52 µM), MCF-7 (IC50 = 0.34 µM) and HT-29 (IC50 = 0.86 µM). Mechanistic studies revealed that compound 7d induced cell apoptosis in a dose-dependent manner, arrested the cells in the G2/M phase and inhibited polymerization of tubulin via a consistent way with colchicine. Therefore, 7d is a potential agent for the further development of tubulin polymerization inhibitors.
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Herein, a ruthenium-mediated remote C-H mono- and disulfonylation of 2-pyridones with arylsulfonyl chlorides is developed. The catalytic system consisting of a [Ru(p-cymene)Cl2]2 catalyst and KOAc additive allows 2-pyridones to undergo C3,C5-disulfonylation in 1,4-dioxane, and C5-sulfonylation when the C3-position of 2-pyridones is blocked. The successful transformation of the products and late-stage modification of estrone further highlighted the potential utility and significance of this synthetic protocol. Preliminary mechanistic studies indicated that the remote regioselectivity might be dictated via chelation-assisted ruthenation.
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An efficient PdII- and RhIII-controlled site-selective C-H bond alkynylation of imidazopyridines using (bromoethynyl)triisopropylsilane is disclosed. The divergent methodology allows straightforward access to a wide range of products alkynylated at the C3 and ortho positions. This strategy is suggestive of a practical platform that can be suitable for late-stage diversification and may assist in the design of more selective and complementary catalytic systems.
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A novel and effective RhIII- and PdII-controlled switchable C-H alkenylation of 2-pyridylthiophenes with alkenes is realized. The alkenylation reactions proceeded smoothly in a highly regio- and stereo-selective manner to afford a broad range of C3- and C5-alkenylated products. Depending on the catalyst employed, the reactions involve two typical approaches: C3-alkenylation via chelation-assisted rhodation and C5-alkenylation via electrophilic palladation. This regiodivergent synthetic protocol was successfully applied for the straightforward building of π-conjugated difunctionalized 2-pyridylthiophenes, which may show great potential in organic electronic materials.
Asunto(s)
Alquenos , Quelantes , Catálisis , Alquenos/químicaRESUMEN
Via aerobic copper-catalyzed tandem quartic C-H aminations, we herein present an unprecedented approach for the synthesis of functionalized benzimidazoles from aniline derivatives and 2-substituted cyclic amines. The cyclic amines act as the CîN building blocks and are involved in the annulation reaction by cleavage of inert α-C-N and ß-C-C bonds. The synthetic protocol features high selectivity, no need for specific aminating agents, mild conditions, and the use of a naturally abundant [Cu]/O2 catalyst system.