Reaction Of Indoles Research Articles

Synthesis of CF3-Substituted N-Heterocyclic Compounds Based on C-H Activation-Initiated Formal [2 + 3] Annulation Featuring with a Latent Nucleophilic Site.

Presented herein is a novel synthesis of CF3-substituted pyrrolo[1,2-a]indole derivatives based on the cascade reactions of N-alkoxycarbamoyl indoles with CF3-ynones. Mechanistically, the formation of a product involves a tandem process initiated by Rh(III)-catalyzed and N-alkoxycarbamoyl group-directed regioselective C2-H alkenylation of the indole scaffold followed by in situ removal of the directing group and intramolecular N-nucleophilic addition/annulation under one set of reaction conditions. To our knowledge, this is the first example in which a N-alkoxycarbamoyl unit initially acts as a directing group for C2-H functionalization of the indole scaffold and is then removed to provide the required reactive NH-moiety for subsequent intramolecular condensation. Moreover, the products thus obtained could be conveniently transformed into structurally and biologically attractive cycloheptenone fused indole derivatives through an acid-promoted cascade transformation. In addition, studies on the activity of selected products against human cancer cell lines demonstrated their potential as lead compounds for the development of novel anticancer drugs.

Skeletal Formation of Carbocycles with CO2: Selective Synthesis of Indolo[3,2-b]carbazoles or Cyclophanes from Indoles, CO2, and Phenylsilane.

The catalytic reactions of indoles with CO2 and phenylsilane afforded indolo[3,2-b]carbazoles, where the fused benzene ring was constructed by forming two C-H bonds and four C-C bonds with two CO2 molecules via deoxygenative conversions. Nine-membered cyclophanes made up of three indoles and three CO2 molecules were also obtained, where the cyclophane framework was constructed by forming six C-H bonds and six C-C bonds. These multicomponent cascade reactions giving completely different carbocycles were switched simply by choosing the solvent, acetonitrile or ethyl acetate.

Phosphoric Acid Catalyzed N-Addition/ C-Addition Reaction of 3-Vinyl Indoles with Pyrazole/Pyrazolone to Construct Pyrazole-Substituted 3-(1-Heteroarylethyl)-indole Scaffolds.

Developing a highly efficient atom-economic method for the preparation of 3-(1-heteroarylethyl)-indole scaffolds is of significant value in pharmaceutical and agricultural chemistry. Herein, a phosphoric acid-catalyzed N-addition reaction of 3-vinyl indoles with pyrazoles and C-addition reaction of 3-vinyl indoles with pyrazolones were developed. A series of pyrazole-substituted 3-(1-heteroarylethyl)-indole scaffolds were synthesized in excellent yields (up to 99% yield) under mild reaction conditions. A reasonable reaction mechanism was proposed to explain the experimental results.

Palladium-Catalyzed Iodine Assisted Carbonylation of Indoles with ClCF2CO2Na and Alcohols.

A palladium-catalyzed iodine-assisted carbonylation reaction of indoles with readily available ClCF2CO2Na and alcohols has been developed. This protocol provides a practical and efficient approach to highly regioselective indole-3-carboxylates via a preiodination strategy of indoles. Different from classic carbonylation using toxic and difficult-to-handle carbon monoxide, this operationally simple and scalable reaction employed difluorocarbene as the carbonyl surrogate.

Enzymatic Synthesis of 3‐Hydroxy Bisindoles and Further C‐3 Sulfenylation via Combining a Carbocatalytic Approach in the Same Pot

AbstractHerein, we report the selective synthesis of 3‐hydroxy bisindoles via an engineered myoglobin‐catalyzed Friedel–Crafts reaction of isatin and indole. Initially, the reaction was carried out using wild‐type myoglobin as a catalyst, but the conversion was low. Therefore, a library of Mb‐variants was generated utilizing a site‐directed mutagenesis technique and obtained the double‐mutated Mb(H64V, V68A) variant as a highly reactive and selective biocatalyst for this transformation. Additionally, the robustness and generality of this protocol have been demonstrated by setting up scale‐up reactions of variously substituted isatins and indoles which produce the desired 3‐hydroxy bisindoles in 66–93 % isolated yield. Next, the enzymatic approach was combined with an carbocatalytic protocol by using graphene oxide as a catalyst to generate C‐3 sulfenylated bisindole derivatives in a one‐pot manner.

Tandem Reactions of Electrophilic Indoles toward Indolizines and Their Subsequent Transformations through Pd(II)-Mediated C-H Functionalization to Access Polyring-Fused N-Heterocycles.

A simple and efficient synthetic approach for generating a library of structurally novel indolizines has been developed via sequential 1,3-dipolar cycloaddition-ring opening processes. Using this methodology, a series of indolizines bearing different substituents were made in moderate to good yields. The presence of two functionalizable C-H bonds in these indolizine motifs makes them attractive for accessing fused indolizine scaffolds. In this line, we have introduced palladium-mediated site-selective C-H functionalizations, where the N-center and the two C-H centers of the indolizine moiety can be readily functionalized to generate fused N-heterocycles. Utilizing a Pd-mediated dual C-H activation of 5-benzoyl-substituted indolizine afforded 6H-indeno-indolizine, and a tetracene, viz., indolizino[2,1-b]indoles, was produced in the same substrate by the Pd-catalyzed selective C-H amination in the presence of oxygen.

Synthesis of 2-Substituted Indoles via Migration Reaction of 3-Substituted Indoles with Triflic Acid.

This study showcases the 1,2-migration reactions of alkyl and aryl groups on the indole molecule. Trifluoromethanesulfonic acid effectively facilitates the migration of the substituent from C3- to C2-position of the indole structure. The resulting C2-substituted indoles offer a valuable pathway for the synthesis of natural products and medicinal compounds.

Visible-Light Mediated Reaction of Indole with Aryl Halides Using Porphyrin Photocatalyst: A Feasible Technique to Afford N-Functionalized Indoles

Visible-Light Mediated Reaction of Indole with Aryl Halides Using Porphyrin Photocatalyst: A Feasible Technique to Afford N-Functionalized Indoles

Chiral Phenol‐2NO Ligand Cooperation with Achiral Organic Base in the Zn(II)‐Catalyzed Asymmetric Alkylation Reaction of Indoles

Comprehensive SummaryThe privileged C2‐symmetric rigid phenol‐type ligand is more attractive but challenging in asymmetric catalysis. Herein, we designed and synthesized a class of rigid‐featured chiral tridentate Phenol‐2NO ligands, that incorporate the advantages of both the phenol skeleton and pyrroloimidazolone‐based N‐oxide moiety, from readily available L‐prolinamides in operationally simple two steps and up to 44% overall yield. More importantly, using an achiral quinoline derivative as an additive, the newly developed Phenol‐2NO ligand could serve as the anioic ligand upon deprotonative activation to coordinate to Zn(II) to form a highly enantioselective catalyst for the asymmetric Michael‐type Friedel‐Crafts alkylation reaction of indoles with 2,3‐dioxopyrrolidines. Excellent yields (up to 90%) and high enantioselectivities (up to 99% ee) are obtained for a wide range of substrates under mild conditions. Experiments and DFT calculations revealed the reaction mechanism and the origins of the enantioselectivity. This also represented the first activation of phenol‐type ligand/metal complex by an achiral organic base as the additive in asymmetric catalysis.

Accessing ladder-shape azetidine-fused indoline pentacycles through intermolecular regiodivergent aza-Paternò–Büchi reactions

Small molecules with conformationally rigid, three-dimensional geometry are highly desirable in drug development, toward which a direct, simple-to-complexity synthetic logic is still of considerable challenges. Here, we report intermolecular aza-[2 + 2] photocycloaddition (the aza-Paternò–Büchi reaction) of indole that facilely assembles planar building blocks into ladder-shape azetidine-fused indoline pentacycles with contiguous quaternary carbons, divergent head-to-head/head-to-tail regioselectivity, and absolute exo stereoselectivity. These products exhibit marked three-dimensionality, many of which possess 3D score values distributed in the highest 0.5% region with reference to structures from DrugBank database. Mechanistic studies elucidated the origin of the observed regio- and stereoselectivities, which arise from distortion-controlled C-N coupling scenarios. This study expands the synthetic repertoire of energy transfer catalysis for accessing structurally intriguing architectures with high molecular complexity and underexplored topological chemical space.

Gallic Acid Derived 1, 2-Diarylindole as a Potential Antifungal Agent against Candida Strain.

In recent decades, Candida albicans has become a serious issue for public health. The worldwide rapid rise in drug resistance to conventional therapies is the main contributing reason. Moreover, because of their potent activity at low concentrations and apparent lack of toxicity, compounds originating from plants are used in therapeutic treatments because of their potent activity at low concentrations and apparent lack of toxicity. Particularly in immunocompromised people, Candida species can result in a wide range of ailments. Present manuscript describes antifungal activity of an indole derivative 1-(4-((5- methoxy-2-(3,4,5-trimethoxyphenyl)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1- amine (7, 100DL-6) by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS- Delhi). The synthetic strategy for the preparation of indole derivatives was modified through Fischer indole reaction. Antifungal activity of an indole derivative 1-(4-((5-methoxy-2-(3,4,5- trimethoxyphenyl)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1-amine (7, 100DL-6) was done by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS-Delhi). Compound 100DL-6 efficacy was determined by Combination synergy study, ergosterol binding assay, MTT toxicity study and Mutagenicity. Compound 100DL-6 was obtained in 65% yield on desired motifs. Docking scores found were 100DL-6 (-8.7 kcal/mol) and Fluconazole (-7.6 kcal/mol). Further, RMSD were shown for 100DL6 (0.26 ± 0.23 nm) and fluconazole (1.2 ± 0.62 nm). Indole derivative 100DL-6 was active against the tested fungal pathogens and the total zone of inhibition was measured between 13-14 mm in diameter and MIC values between 31.25 μg/mL to 250 μg/mL and MFC values between 62.5 μg/mL to 500 μg/mL. In checkerboard assay synergistic mode of interaction of 100DL-6 with known antifungal drugs was observed. In the presence of ergosterol 100DL-6 and standard drug (s) increased their MIC values, demonstrating a considerable affinity for ergosterol. Compound 100DL-6 was considered to be less-cytotoxic to the cells as determined by MTT assay. Lead compound 100DL-6 was found to be non-mutagenic. In the present study, 100DL6 (indole derivatives) significantly abrupted the ergosterol biosynthetic pathway and showed moderate anti-candidal effects. These studies suggest that 100DL6 significantly enhances antifungal effect of clinical drug fluconazole synergistically and may be considered as in clinical trial prior to some extensive in-vivo validations.

Cu(I)-based chiral catalysts bearing binaphthyl-Proline hybrid ligands and their application in enantioselective Friedel-Crafts reactions of indoles with isatins

Highly enantioselective Friedel-Crafts reactions of indoles with isatins were realized using chiral Cu(I) catalyst bearing BINOL and proline-based electronically and sterically tunable chiral O–N–N tridentate ligands. Such catalyst system showed excellent performance in enantioselective Friedel-Crafts alkylation of different indoles, and a series of 3-indolyl-3-hydroxyoxindoles were obtained in high yields (90–98 %) and excellent enantioselectivities (82–98 % ee) under mild reaction conditions.

Sustainable Synthesis of Indole-Substituted Densely Functionalized Pyrrole.

A novel chromatography- and catalyst-free methodology has been developed for the synthesis of poly substituted pyrrole in good yields via a multicomponent reaction of arylglyoxal, 1,3-dicarbonyl, indole, and aromatic amine. This strategy provides various advantages such as simple experimental and workup procedures, mild reaction conditions, no added catalyst, use of green solvent, and simple purification procedure of pure product without using column chromatography. This green method offers a simple and highly effective strategy to synthesize a wide range of indole-pyrrole conjugates in a one-pot operation.

Dearomative spiroannulation of indoles enabled by the diaza-[1,2]-Wittig rearrangement

Reported herein is the first diaza-[1,2]-Wittig rearrangement-enabled dearomative spiroannulation reaction of indoles. This protocol features metal-free conditions, a redox-neutral process, a broad substrate scope, and a good yield.

Enantioselective Synthesis of Unsymmetrical α,α-Diarylacetates via Organocatalyzed Formal C-H Insertion Reactions of Sulfoxonium Ylides with Indoles and Pyrroles

The chiral unsymmetrical α,α-diarylmethine skeleton is widely found in natural products and synthetic pharmaceuticals. The catalytic asymmetric C-H insertion reaction of simple, unprotected indoles and pyrroles with α-aryl sulfur ylides...

Molecular identification and antibiotic resistance profiling of Vibrio spp. in diarrhoeal patients from Dinajpur, Bangladesh

This research aimed to characterize Vibrio species from cholera-suspected patients in three hospitals in Dinajpur. We collected 36 stool samples and identified Vibrio spp. using cultural, morphological, and biochemical tests. The highest prevalence was observed in children (18.18%), compared to adolescents (0%), adults (16.67%), and senior adults (16.67%). Cultural identification revealed yellow colonies on TCBS agar, hemolytic colonies on blood agar, pale non-lactose fermenting colonies on MacConkey agar, and white, opaque colonies on nutrient agar. Gram staining showed gram-negative, curved rod-shaped bacteria. Biochemical tests indicated positive reactions for oxidase, catalase, MR, TSI, citrate utilization, MIU, and indole, while VP was negative. Molecular characterization by PCR and gel electrophoresis using 16S rRNA primers confirmed the presence of Vibrio spp. Antibiotic sensitivity testing showed that isolates were sensitive to cotrimoxazole-25µg (21 mm to 30 mm), neomycin-30µg (22 mm), gentamycin-10µg (15 mm), streptomycin-10µg (20 mm), and tetracycline-30µg (17 mm), but resistant to penicillin, mecillinam, and amoxicillin. These findings suggest streptomycin and cotrimoxazole as effective drugs for controlling cholera.

The use of a tertiary solvent mixture to study solvent dynamic effects in the photoinduced electron transfer reaction of excited singlet pyrene and indole

The solvent dynamic effects in the PET reactions were studied in a series of tertiary solvent mixtures PA/BN/DEP, spanning a wide range of dielectric constants (5.90 < εs < 23.4) while maintaining refractive index and viscosity constant.

A Mn(iii)-catalyzed arylboronic acid-based cascade reaction via a nonclassical organometallic-radical mechanism

An efficient Mn(iii)-catalyzed cascade reaction of arylboronic acids, o-cyanoaryl isocyanides, and indoles was developed. The mechanism was fully investigated and elucidated.

Recent advances in oxidative dearomatization involving C-H bonds for constructing value-added oxindoles.

Exploring three-dimensional chemical space is an important research objective of organic synthetic chemistry. Oxidative dearomatization (ODA) is one of the most important and powerful tools for realizing this goal, because it changes and removes aromatic structures from aromatic compounds to increase levels of saturation and stereoisomerism by direct addition reactions between functional groups with aromatic cores under oxidative conditions. As a hot topic in indole chemistry, the synthetic value of the oxidative dearomatization of indoles has been well recognized and has witnessed rapid development recently, since it could provide convenient and unprecedented access to fabricate high-value-added three-dimensional oxindole skeletons, such as C-quaternary indolones, polycycloindolones and spiroindolones, and be widely applied to the total synthesis of these oxindole alkaloids. Therefore, this article provides a review of recent developments in oxidative dearomatization involving the C-H bonds of indoles. In this article, the features and mechanisms of different types of ODA reactions of indoles are summarized and represented, and asymmetric synthesis methods and their applications are illustrated with examples, and future development trends in this field are predicted at the end.

Py-2NO ligand enabled Ni(ii)-catalyzed asymmetric Michael addition reaction of indoles with β,γ-unsaturated α-keto esters

This work diversified the Py-2NO ligand library recently developed by our group and further expanded the application of chiral Py-2NO ligands in asymmetric catalysis.