2-Pyridone-Directed CuII-Catalyzed General Method of C(sp2)-H Activation for C-S, C-Se, and C-N Cross-Coupling: Easy Access to Aryl Thioethers, Selenide Ethers, and Sulfonamides and DFT Study.

We have demonstrated N-substituted 2-pyridones as an N,O-directing group for selective C(sp2)-H-activated thiolation, selenylation, and sulfonamidation of ortho C-H bonds of benzamides. This method utilizes a cost-effective Cu(II)-salt catalyst instead of precious metal catalysts, achieving high yields, including gram-scale synthesis and excellent functional group tolerance. We applied this protocol to access 30 different compounds with high yields, demonstrating thiolation of fluorine-substituted benzamides as well. Density functional theory (DFT) calculations support the mechanism, including acetate-supported concerted metalation deprotonation (CMD) steps and the unique role of dimethyl sulfoxide (DMSO) solvent. The facile synthesis of pharmaceutically important sulfonamides and other compounds highlights the method's potential in chemistry and medicinal chemistry.

Hybrid Heterocycles: Ag(I)-Catalyzed C-C/C-N/C-O Coupled Cascade Dual Cyclization to Valuable Indolo-4H-indolones and Indolo-4H-chromenes.

Herein, we report a highly efficient Ag(I)-catalyzed indolyzation with Friedel-Crafts alkylation through a cascade cyclization strategy for accessing valuable hybrid heterocycles for the first time. This general strategy consists of forming four C-C/C-N/C-O bonds toward dual annulation reactions of 2-alkynylanilines with methyl benzoate-2-carboxaldehydes and aromatic amines, as well as with salicylaldehydes and malononitrile. Variably substituted new indolo-4H-phthalimidines and indolo-4H-chromenes were synthesized with excellent yields (85-93%) under mild reaction conditions.

BroÌ·nsted Acid-Catalyzed [5+1] and [4+1] Annulation of Cyclic Anhydrides with o-Alkynylanilines to Construct Fused-N-Heterocycles.

An unprecedented p-TsOH and MsOH-catalyzed construction of valuable isoindolo/pyrido/pyrrolo-quinolinediones and isoindolo-indolones is demonstrated through annulation reactions of cyclic anhydrides or o-formylbenzoates with o-alkynylanilines. The metal-free BroÌ·nsted acid-mediated new [5+1] and [4+1] fused-cyclization is an operationally simple, highly regioselective, atom economical, high yielding, sustainable, and catalytically efficient approach.

Synthesis of Functionalized Arylacetamido-2-pyridones through ortho-C(sp2)-H-Activated Installation of Olefins and Alkynes.

We have identified different N-substituted 2-pyridones as inbuilt directing groups for selective C-H-activated functionalization instead of deprotecting and/or throwing away the directing groups. A robust general method for external ligand-free PdII-catalyzed C(sp2)-H olefination and alkynylation is established to access valuable phenylacetamido-2-pyridones. Diverse substrate scope has been demonstrated with 48 different examples with high yield and gram-scale synthesis. Adequate tolerance of valuable functional groups was also observed, such as olefins possessing esters, sulfone, amide, cyanide, and ketones, aromatic residues containing fluorine, chlorine, bromine, NO2, methyl, dimethyl, and methoxy, as well as 2-pyridone-N-bearing methyl, cyclopropyl methyl, cyclopentyl methyl, benzyl, phenyl, acetate, and acetamide groups, which smoothly produced the respective desired products. We used triisopropyl silane-substituted alkynes for the alkynylation reaction, which can easily be converted to several functional groups including terminal alkyne, heterocycle through click reaction, and others. Implementing our protocol, we have also demonstrated late-stage olefination and alkynylation of 2-pyridone, containing the CB2 agonist-type molecule with excellent yield. Considering N-substituted 2-pyridone acts as a biologically-active structural unit, this general method has the significance in terms of late-stage functionalization to access new molecular entities which can be employed in medicinal chemistry research through diverse C-H activation.

A competitive and highly selective 7-, 6- and 5-annulation with 1,3-migration through C-H and N-H - alkyne coupling.

We demonstrated a highly competitive and selective C-C and N-C cross-coupled 7-, 6- and 5-annulation utilizing 2-ethynylanilides to afford functionalized 1H-benzo[b]azepin-2(5H)-ones, 2-quinolinones, and 3-acylindoles in high yield. ZnCl2 was found to be the smart catalyst for 7- and 5-annulation with 1,3-migration through C-H and N-H functionalization, respectively, whereas molecular iodine performed the C-H functionalized 6-annulation with a nonconventional 1,3 H-shift. The mechanism was investigated by intermediate trapping, control, and labeling experiments.

5-Annulation of Ketoimines: TFA-Catalyzed Construction of Isoindolinone-3-carboxylates and Development of Photophysical Properties.

Herein we have demonstrated the first report on 5-annulation of ketoimines to valuable isoindolinone-3-carboxylates. Instead of commonly used aldimine substrates, relatively less reactive ketoimines are employed for developing a TFA catalyzed organoreductive cyclization to furnish a variety of isoindolinones in excellent yield and reaction rate under mild reaction conditions. This is a metal-free event, which proceeds through a one pot ketoimine formation, hydride transfer from an organic reductant 2-(naphthalen-2-yl)-2,3-dihydrobenzo[ d]thiazole, and followed by five member cyclization sequences through TFA-activation of imine and ester groups. Studies on ESI-MS kinetics, leaving group aptitude, and control experiments led us to propose the mechanistic pathway of the new ketoimine-lactamization reaction. We have shown the synthetic utility of the emerging synthons through easy transformation of isoindolinones to different synthetic analogues. We investigated photophysical properties of the small molecules for their futuristic application as a pharmaceutical and materials, and the heterocycles displayed brilliant fluorescence activity.