Iron-Catalyzed Friedel-Crafts-type 3,5-Diacylation of Indoles.

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.

Organoselenium-Catalyzed C2,3-Diarylation of N-H Indoles.

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.

Cu-Co Dual-Atom Catalysts Supported on Hierarchical USY Zeolites for an Efficient Cross-Dehydrogenative C(sp2)-N Coupling Reaction.

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.

Iodine-Mediated C2,3-H Aminoheteroarylation of Indoles.

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.

Design and Synthesis of (3-Phenylisoxazol-5-yl)methanimine Derivatives as Hepatitis B Virus Inhibitors.

Series of (3-phenylisoxazol-5-yl)methanimine derivatives were synthesized, and evaluated for anti-hepatitis B virus (HBV) activity in 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 0.65 µM (3TC(Lamivudine) in 189.90 µM), inhibited HBV DNA in 20.52 µM (3TC in 26.23 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.

Intermolecular C-H Aminocyanation of Indoles via Copper-iodine Cocatalyzed Tandem C-N/C-C Bond Formation.

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 carbon═carbon 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.

Synthesis of 3-halogenated 2,3'-biindoles by a copper-mediated 2,3-difunctionalization of indoles.

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.

Silver-mediated three-component cycloaddition reaction for direct synthesis of 1-N-vinyl-substituted 1,2,3-triazoles.

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.

Iodine-dependent oxidative regioselective aminochalcogenation of indolines.

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.

Iodine-mediated oxidative triple functionalization of indolines with azoles and diazonium salts.

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.

Regiodivergent C-H alkynylation of 2-arylthiazoles switched by RuII and PdII catalysis.

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.

Synthesis and bioactive evaluation of N-((1-methyl-1H-indol-3-yl)methyl)-N-(3,4,5-trimethoxyphenyl)acetamide derivatives as agents for inhibiting tubulin polymerization.

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.

Unlocking Regiodivergence in PdII- and RhIII-Mediated Site-Selective C-H Bond Alkynylation of Imidazopyridines.

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.

Ruthenium(II)-Catalyzed Remote C-H Sulfonylation of 2-Pyridones.

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.

Catalyst-controlled regiodivergent C-H bond alkenylation of 2-pyridylthiophenes.

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.

Synthesis of functionalized benzimidazoles via oxidative tandem quartic C-H aminations and cleavage of C-N and C-C bonds.

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 CN 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.

Straightforward access to novel indolo[2,3-b]indoles via aerobic copper-catalyzed [3+2] annulation of diarylamines and indoles.

Herein, we report an unprecedented aerobic copper-catalyzed [3+2] annulation reaction of diarylamines with indoles, which allows direct access to novel 2-diarylaminoindolo[2,3-b]indoles, a class of potential photoelectric device molecules. The developed transformation proceeds with broad substrate scope, good functional group tolerance, high chemo-selectivity, and no need for pre-preparation of specific agents, which offers a practical route for diverse and atom-economic synthesis of the desired products that are difficult to prepare with the conventional approaches.

Synthesis of Multisubstituted Benzimidazolones via Copper-Catalyzed Oxidative Tandem C-H Aminations and Alkyl Deconstructive Carbofunctionalization.

Benzimidazolone constitutes the core structure of numerous pharmaceuticals, agrochemicals, inhibitors, pigments, herbicides, and fine chemicals. Amination of hydrocarbons is an attractive tool for the creation of nitrogen-containing products. However, the multiple steps, harsh conditions, and low atom efficiencies often present in these reactions remain challenging. We present a multicomponent synthesis of functional benzimidazolones from arylamines, dialkylamines, and alcohols, acting via the sequence of copper-catalyzed oxidative tandem C-H aminations and alkyl deconstructive carbofunctionalization. The catalytic transformation forms multiple bonds in one single operation, uses readily available feedstocks and a naturally abundant Cu/O2 catalyst system, has broad substrate scope, avoids pre-installation of aminating agents and directing groups, and provides high chemo- and regioselectivity, resulting in direct functionalization of inert C-H and C-C bonds via single-electron oxidation-induced activation mode. This platform can be expected to provide structurally diverse products with interesting biological, chemical, and physical properties.

Direct Access to Functionalized Indoles via Single Electron Oxidation Induced Coupling of Diarylamines with 1,3-Dicarbonyl Compounds.

Under aerobic copper catalysis, an unprecedented direct synthesis of functionalized indoles via single electron oxidation induced coupling of diarylamines with 1,3-dicarbonyl compounds is presented. The protocol proceeds with good functional group and substrate compatibility, the use of readily available feedstocks and naturally abundant catalyst system, high step and atom efficiency, as well as selectivity, which offers a platform for accessing a new class of indoles with the potential for the discovery of functional molecules.