Photoredox Hydroxy-arylation of the Terminal Double Bond of <i>N</i>‑Substituted 3‑Methyleneisoindolin-1-ones in Visible Light

Mild and efficient ruthenium-catalyzed hydroxy-arylation of the terminal double bond of N-substituted 3-methyleneisoindolin-1-ones is described. The reaction takes place with aryl diazonium salt as the arylating reagent and water as the hydroxyl source in visible light at ambient temperature. The strategy entails vicinal difunctionalization of alkene and enables construction of 3-benzyl-3-hydroxyisoindolin-1-one heterocyclic scaffolds in moderate to good yields. C–C and C–O bonds are formed in one pot without any external additive and oxidant through an in situ generation of a carbocation intermediate in green light

Design, Synthesis, and Antibacterial Evaluation of Oxazolidinones with Fused Heterocyclic C‑Ring Substructure

A series of novel oxazolidinone antibacterials with diverse fused heteroaryl C-rings bearing hydrogen bond donor and hydrogen bond acceptor functionalities were designed and synthesized. The compound with benzoxazinone C-ring substructure (<b>8c</b>) exhibited superior activity compared to linezolid against a panel of Gram-positive and Gram-negative bacteria. Structural modifications at C5-side chain of <b>8c</b> resulted in identification of several potent compounds (<b>12a</b>, <b>12b</b>, <b>12g</b>, and <b>12h</b>). Selected compounds <b>8c</b> and <b>12a</b> showed very good microsomal stability and no CYP₄₅₀ liability, thus clearing preliminary safety hurdles. A docking model of <b>12a</b> binding to 23S rRNA suggested that the increased potency of <b>12a</b> is due to additional ligand–receptor interaction

Palladium-Catalyzed Regioselective Decarboxylative Alkylation of Arenes and Heteroarenes with Aliphatic Carboxylic Acids

An unprecedented Pd­(OAc)₂-catalyzed decarboxylative alkylation of unactivated arenes, with aliphatic carboxylic acids as inexpensive alkyl sources, is reported. The alkylation, controlled by the directing group, is regioselective, shows high functional group tolerance, and provides mild access to alkylated indolines, 2-phenylpyridines, and azobenzenes under solvent-free conditions in moderate to high yields

Copper Acetate–DMSO Promoted Methylthiolation of Arenes and Heteroarenes

An unprecedented copper acetate–DMSO promoted methylthiolation of arenes and heteroarenes in the presence of air has been developed. The reaction is highly regioselective under the directing group influence of pyridine and pyrimidine functional units and gives the thiomethylated product in moderate to high yields

One-Pot Sequential Alkynylation and Cycloaddition: Regioselective Construction and Biological Evaluation of Novel Benzoxazole–Triazole Derivatives

Individually, benzoxazole and triazole moieties are of significant biological interest owing to their importance in drugs and pharmaceuticals. To assess their combined biological impact when woven into one molecule, we designed a novel, regioselective, multicomponent, one-pot (MCOP) approach for the construction of benzoxazole-linked triazoles. The synthesis has been achieved in two sequential steps involving copper-catalyzed alkynylation of benzoxazole followed by a 1,3-dipolar cycloaddition reaction. By combination of these two bioactive units into one core, a series of new benzoxazole-triazole scaffolds has been synthesized and subjected to in vitro antibacterial and anticancer evaluation. Tests against clinical isolates of <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> showed potent Gram-negative activity for compounds <b>4</b>{<i>1,1,1</i>}, <b>4</b>{<i>1,1,4</i>}, and <b>4</b>{<i>1,2,1</i>}. The cytotoxicity of the synthesized library was determined against three cancer cell lines: HeLa, SKBr3, and Hep G2. Compound <b>4</b>{<i>2,2,2</i>} showed significant cytotoxicity against all the cell lines. These preliminary bioassay evaluations strongly suggest the promise and scope of these novel molecules as therapeutic agents in medical science

<i>N</i>‑Mannich Bases of Aromatic Heterocyclic Amides: Synthesis via Copper-Catalyzed Aerobic Cross-Dehydrogenative Coupling under Ambient Conditions

An efficient and facile method to synthesize <i>N</i>-Mannich bases has been developed using an inexpensive copper­(I) bromide/air catalyst system at ambient temperature. A cross-dehydrogenative coupling of <i>N,N</i>-dimethylarylamines occurs efficiently with aromatic heterocyclic amides (oxindoles, isatins), cyclic amides (lactams), simple amides (benzamide), as well as imides (succinimide, phthalimide) to furnish the corresponding amidated/imidated derivatives in good to excellent yields. Preliminary mechanistic and isotope-labeling studies suggest the reaction follows a radical pathway and involves an iminium ion intermediate

Palladium Catalyzed Carbonylative Coupling for Synthesis of Arylketones and Arylesters Using Chloroform as the Carbon Monoxide Source

We describe a modular, palladium catalyzed synthesis of aryl­(hetero)­aryl benzophenones and aryl benzoates from aryl­(hetero)­aryl halides using CHCl₃ as the carbonyl source in the presence of KOH. The reaction occurs in tandem through an initial carbonylation to generate an aroyl halide, which undergoes coupling with arylboronic acids, bornonates, and phenols. Direct carbonylative coupling of indoles at the third position has also been accomplished under slightly modified reaction conditions by <i>in situ</i> activation of the C–H bond. Notably, CHCl₃ is a convenient and safe alternation of CO gas, provides milder reaction conditions with high functional group tolerance, and gives the products in moderate to good yields

Regioselective Synthesis of <i>N</i>²‑Alkylated-1,2,3 Triazoles and <i>N</i>¹‑Alkylated Benzotriazoles: Cu₂S as a Recyclable Nanocatalyst for Oxidative Amination of <i>N</i>,<i>N</i>‑Dimethylbenzylamines

Copper chalcogenide nanoparticles (Cu₂S) synthesized for the first time from a single-source precursor, CuSPh, act as highly efficient and reusable heterogeneous catalyst for regioselective amination of <i>N</i>,<i>N</i>-dimethylbenzylamines with various azoles. The reaction involves N–H/C–H cross-dehydrogenative coupling (CDC) and demonstrates wide functional group tolerance. It provides highly selective access to <i>N</i>¹-alkylated benzotriazoles, <i>N</i>²-alkylated 1,2,3-triazoles and 4-phenyl-1,2,3-triazoles, and <i>N</i>-alkylated carbazoles in 70–89% yields under solvent-free conditions. The Cu₂S nanocatalyst has been characterized by PXRD, XPS, SEM–EDX, and HR–TEM analysis. Mechanistic studies suggest that the reaction follows a radical pathway and involves an iminium ion intermediate

Zinc Triflate Catalyzed C‑Benzylation: Chemo- and Regioselective Route to Amido Substituted Diaryl and Arylheteroarylmethanes

An unprecedented zinc triflate catalyzed selective C-benzylation of anilides and heteroaryl amides with benzyl chlorides having electron-donating group at <i>para</i>-position is reported. The protocol offers moderate to high yield of <i>para</i>-amido substituted diaryl and arylheteroarylmethanes, uses cheap and easily available benzyl chlorides as the benzylating agent, catalytic amount of zinc triflate, and takes place under ambient conditions. Aminodiarylmethane derivatives can be obtained by hydrolysis of the corresponding amides. The methodology has also been applied for preparing dimethoxydiarylmethanes in good yields, which are the key precursors for synthesis of phenolic natural products

Copper-Catalyzed <i>anti</i>-Markovnikov Hydroindolation of Terminal Alkynes: Regioselective Synthesis of Bis(indolyl)alkanes

An efficient copper-catalyzed intermolecular hydroindolation reaction of terminal aryl alkynes to expeditiously synthesize bis­(indolyl)­alkanes in moderate to high yields is described. The double nucleophilic addition of two molecules of indole to one molecule of alkyne occurs in a tandem manner through an <i>anti-</i>Markovnikov pathway. Various arenes and alkynes allow for this transformation. Preliminary mechanistic study sheds light on the observed regioselectivity involving a Cu-vinylidene complex, and 3-styryl-1H-indole as probable intermediates