I2-Cs2CO3 Mediated Intramolecular C2-Amination and Oxidative Rearrangement Cascade of C-3 Phenylthio Indoles: A Route to Synthesize Thiosulfonate-Embedded 2-Iminoindolin-3-ones.

An efficient, transition-metal-free protocol employing I2/Cs2CO3 for the synthesis of thiosulfonate containing 2-iminoindolin-3-ones motifs has been developed from C-3 phenylthio indoles. The reaction proceeded through intramolecular cyclization involving C-N bond formation, leading to the formation of indole-fused benzothiazines as a key intermediate. Remarkably, Cs2CO3 played a crucial role in the reaction as an oxygen source, enabling oxidative rearrangement with [1,4]-sulfonyl migration to furnish the final products with the formation of multiple functional groups such as C═O, C═N, and S-SO2.

Iodine-promoted sequential C(sp3)-H oxidation and cyclization of aryl methyl ketones with 2-(2-aminophenyl)quinazolin-4(3H)-ones.

An I2-promoted, metal-free protocol has been developed for the one-pot synthesis of 6-aroyl-5,6-dihydro-8H-quinazolino[4,3-b]quinazolin-8-ones from readily accessible substrates. This reaction involves the in situ sp3 C-H oxidation of aryl methyl ketones to phenylglyoxal, followed by imine formation and intramolecular nucleophilic addition, resulting in the formation of two new C-N bonds. Furthermore, the method is applicable to a wide range of aryl methyl ketones, including heterocycles and drug-derived substrates, yielding the desired products with yields ranging from 62% to 93%. Additionally, the practical utility of this approach was demonstrated through gram-scale synthesis.

I2-catalyzed tandem sp3 C-H oxidation and annulation of aryl methyl ketones with amidoximes for the synthesis of 5-aroyl-1,2,4-oxadiazoles.

A metal-free, iodine-catalyzed protocol has been developed for constructing biologically significant 5-aroyl 1,2,4-oxadiazole scaffolds using aryl methyl ketones and amidoximes. The strategy produces structurally diverse 5-aroyl 1,2,4-oxadiazoles in good to excellent yields, with a broad substrate scope that includes drug derived substrates. The reaction proceeds through iodine/DMSO-mediated oxidation of aryl methyl ketones, followed by imine formation and subsequent cyclization to yield the desired products. Additionally, this protocol has successfully produced the carbonyl analogs of ataluren and tioxazafen and has facilitated some intriguing late-stage transformations.

Synthesis of Di(thiophen-2-yl) Substituted Pyrene-Pyridine Conjugated Scaffold and DFT Insights: A Selective and Sensitive Colorimetric, and Ratiometric Fluorescent Sensor for Fe(III) Ions.

In this context, we used the multicomponent Chichibabin pyridine synthesis reaction to synthesize a novel di(thiophen-2-yl) substituted and pyrene-pyridine fluorescent molecular hybrid. The computational (DFT and TD-DFT) and experimental investigations were performed to understand the photophysical properties of the synthesized new structural scaffold. The synthesized ligand displays highly selective fluorescent sensing properties towards Fe3+ ions when compared to other competitive metal ions (Al3+, Ba2+, Ca2+, Cd2+, Co2+, Cr3+, Cu2+, Fe2+, Hg2+, Na+, Ni2+, Pb2+, Sr2+, Sn2+ and Zn2+). The photophysical properties studies reveal that the synthesized hybrid molecule has a binding constant of 2.30 × 103 M-1 with limit of detection (LOD) of 4.56 × 10-5 M (absorbance mode) and 5.84 × 10-5 M (emission mode) for Fe3+ ions. We believe that the synthesized pyrene-conjugated hybrid ligand can serve as a potential fluorescent chemosensor for the selective and specific detection of Fe3+ ions.

Iodine-Catalyzed Synthesis of Benzo-ß-carbolines through Desulfurative Cyclization of 2-(1H-Indol-3-ylsulfanyl)-phenylamines with Aryl Methyl Ketones.

A novel transition metal-free strategy for the synthesis of benzene-fused ß-carboline scaffolds has been developed. This protocol offers a rapid and direct pathway to access the benzene fused ß-carboline from 2-(1H-indol-3-ylsulfanyl)-phenylamines and aryl methyl ketones using an efficient catalytic system of I2/DMSO. The present mild protocol proceeds through the sequential reactions of Kornblum oxidation, Pictet-Spengler cyclization, and desulfurization to afford the desired products in excellent yields up to 99%. Moreover, this method has a wide range of substrate tolerance and is operationally simple and applicable in gram-scale synthesis.

Multicomponent Reaction Based Tolyl-substituted and Pyrene-Pyridine Conjugated Isomeric Ratiometric Fluorescent Probes: A Comparative Investigation of Photophysical and Hg(II)-Sensing Behaviors.

Herein, the synthesis of pyrene conjugated 2,6-di-ortho-tolylpyridine and 2,6-di-para-tolylpyridine structural isomers were achieved efficiently through multicomponent Chichibabin pyridine synthesis reaction. The DFT, TD-DFT and experimental investigations were carried out to investigate the photophysical behaviors of the synthesized novel pyrene-pyridine based isomeric probes. Our studies revealed that, due to the continuous conjugation of the pyrene, pyridine and tolyl moieties, the dihedral angles of the trisubstituents on the central pyridine moiety significantly influences the photophysical properties of the synthesized novel pyrene based fluorescent probes. Further, we have comparatively investigated the sensing behaviors of the synthesized tolyl-substituted isomeric ratiometric fluorescent probes with metal ions, our studies reveals that both the ortho and para tolyl ratiometric fluorescent probes have distinct photoemissive properties in selectively sensing of Hg2+ ions. Our studies indicates that, the para-tolyl substituted isomer displays more red-shift in wavelength of emission band compared to its ortho isomer analogue during ratiometric fluorescent specific detection of Hg2+ ions.

A one-pot metal-free protocol for the synthesis of chalcogenated furans from 1,4-enediones and thiols.

Transition-metal-free synthesis of chalcogenated furans through the sequential thiol-Michael/Paal-Knorr reaction of 1,4-enediones in the presence of a catalytic amount of p-toluenesulfonic acid has been developed. The present one-pot strategy involves the thiol Michael addition to 1,4-enediones in an anti-Markovnikov fashion with the formation of a new C-S bond, followed by intramolecular dehydrative annulation in the presence of cat. TsOH delivering fully substituted furans in good to excellent yields (50-99%). The reaction is compatible with a wide range of substrates and also capable of multi-gram scale synthesis of chalcogenated furans.

Iodine mediated intramolecular C2-amidative cyclization of indoles: a facile access to indole fused tetracycles.

A novel and metal-free I2-mediated intramolecular C2 amidation of indoles under mild reaction conditions is developed. This methodology affords various indole fused tetracyclic compounds, such as benzo[4,5]imidazo[1,2-a]indoles by intramolecular C2 amidation of N-aryl substituted indoles. This C2 sulfonamidative cyclization also offers convenient access to indolo[2,3-b]indoles and dihydroindolo[2,3-b]quinoline from C3 aryl substituted indoles in good to excellent yields. Indolo[2,3-b]quinolines are also synthesized by the domino cyclization-detosylation-aromatization reaction sequence.

An efficient route to synthesize isatins by metal-free, iodine-catalyzed sequential C(sp(3))-H oxidation and intramolecular C-N bond formation of 2'-aminoacetophenones.

A novel molecular I2-catalyzed synthesis of isatins through C(sp(3))-H oxidation and intramolecular C-N bond formation of 2'-aminoacetophenones with excellent yields up to 97% under transition metal, base, additive, peroxide and ligand free conditions is described. The present protocol is suitable for gram scale synthesis of isatins and retained its high yield. Further, the synthetic utility of this present reaction towards synthesis of bioactive 3-hydroxy-2-oxindoles and oxindoles is demonstrated.

Annulation of benzamides with [60]fullerene through palladium(II)-catalyzed C-H bond activation.

Palladium-catalyzed heteroannulation of N-substituted benzamides with [60]fullerene, which proceeds through direct sp(2) C-H bond activation to form 7-membered ring pallada-intermediate with C(60), led to formation of [60]fulleroisoquinolinones in moderate to good yields (8-64% based on recovered C(60)). A plausible reaction pathway is proposed.

Synthesis and Properties of Bis-corannulenes.

Corannulenecarbaldehyde and corannulenylmethyl triphenylphosphonium bromide are combined through the Wittig olefination reaction to furnish dicorannulenylethene with 70% yield. A subsequent oxidative photocyclization leads to annulation of the corannulene nuclei to produce a C42H18 nanographene structure in 59% yield. Interestingly, only the trans isomer of the dicorannulenylethene forms cocrystals with fullerene C60 through concave-convex and convex-convex π-π stacking interactions. The Mallory photocyclization could be extended to a phenanthrene-based diarylethene precursor to yield a large bicorannulene system.

A photochemical approach to aromatic extension of the corannulene nucleus.

A high yielding, general, and mild synthetic strategy is established for aromatic annulation of the corannulene scaffold. In this approach, a corannulene-based aldehyde, ylide, or ketone compound is conjugated with an aromatic unit of choice through a Wittig reaction. The resulting stilbene-like precursor can be subjected to a photochemically induced oxidative-cyclization process to yield a corannulene structure with an extended π-framework. The generality of synthesis allows for preparation of a wide range of polycyclic aromatic arene as well as heteroarene structures. Meanwhile, the mild nature of the developed protocol permits for incorporation of reactive and functional substituents onto the fused aromatic scaffold. Furthermore, efficient and simple synthesis ensures access to significant amounts of the material in a facile manner. In essence, this work demonstrates, for the first time, that photochemical synthesis is a highly practical alternative to the known flash vacuum pyrolysis and metal catalyzed processes for the aromatic extension of the bucky-bowl structure.

A versatile and one-pot strategy to synthesize α-amino ketones from benzylic secondary alcohols using N-bromosuccinimide.

A metal-free one-pot strategy has been developed for the first time to synthesize pharmaceutically important α-amino ketones from readily available benzylic secondary alcohols and amines using N-bromosuccinimide. This new reaction proceeds via three consecutive steps involving oxidation of alcohols, α-bromination of ketones, and nucleophilic substitution of α-bromo ketones to give α-amino ketones. Importantly, this novel one-pot greener reaction avoids direct usage of toxic and corrosive bromine. This methodology has been employed efficiently to synthesize pharmaceutically important amfepramone and pyrovalerone in a single step.

Palladium-catalyzed oxidative insertion of carbon monoxide to N-sulfonyl-2-aminobiaryls through C-H bond activation: access to bioactive phenanthridinone derivatives in one pot.

Palladium-catalyzed oxidative carbonylation of N-sulfonyl-2-aminobiaryls through C-H bond activation and C-C, C-N bond formation under TFA-free and milder conditions has been developed. The reaction tolerates a variety of substrates and provides biologically important phenanthridinone derivatives in yields up to 94%.