Developing a straightforward route toward the synthesis of arylaminomaleimides by palladium-catalyzed arylation of one-pot synthesized aminomaleimides.

3-Aryl-4-aminomaleimides have well-demonstrated applications, such as being used as fluorophores and inhibitors. However, their previous synthesis methods have involved tedious multi-step procedures or methods that need pre-functionalized maleimides and toxic or unstable reagents. Here, a feasible method is developed to synthesize these useful compounds. This includes the one-pot preparation of 3-aminomaleimides, followed by their direct arylation through a palladium-catalyzed Heck reaction with various aryl iodides regioselectively at the ß-position of their amine substituents. The results show that this method efficiently exhibits a broad scope.

Dual Role of Oxoaldehydes: Divergent Synthesis of 3-Aryl- and 3-Aroylcoumarins.

A facile and efficient synthetic approach to various valuable 3-aryl- and 3-aroylcoumarins by the direct arylation and aroylation of coumarins with glyoxals in a metal-free manner is presented. The aryl glyoxal is for the first time recognized to serve as an aryl surrogate in addition to its role as an aroyl transfer reagent via a simple switch in reaction conditions. The approach accommodates a broad substrate scope and high yields of the two types of cross-coupling reactions starting from identical starting materials.

Transition-metal-free oxidative cyclization reaction of enynals to access pyrane-2-one derivatives.

A novel and efficient metal-free C-H functionalization of enynals is developed to synthesize α-pyrone derivatives via the formation of two C-O bonds. In this project, K2S2O8 has been introduced as an efficient oxygen source and C-H functionalization agent in regioselective oxidative cyclization reaction with a relatively broad substrate scope.

Divergent Synthesis of α-Aroyloxy Ketones and Indenones: A Controlled Domino Radical Reaction for Di- and Trifunctionalization of Alkynes.

Three different modes of aldehyde/alkyne assembly through a controlled radical reaction are devised. While a double C-H activation/annulation leads to indenones, a concurrent oxidation of both aldehydes and alkynes in the course of their connection offers aroyloxy ketones. Besides two types of cascade reactions starting from identical materials, through a phenylpropiolic acid substrate, a cascade three C-C bond formation via an uninterrupted C-H functionalization/annulation/decarboxylative aroylation as a formidable challenge in radical reactions occurs to deliver 2-aroyl-3-aryl indenones.

Peroxy mediated Csp2-Csp3 dehydrogenative coupling: regioselective functionalization of coumarins and coumarin-3-carboxylic acids.

A regioselective direct alkylation of coumarins at C-3 via cross-dehydrogenative coupling of unactivated Csp2-Csp3 bonds is developed. This protocol employs tert-butyl hydroperoxide as the sole reagent of the reaction to combine coumarins and ethers in reasonable yields under metal- and solvent-free reaction conditions. This protocol also worked well with coumarin-3-carboxylic acids to unveil a rare instance of a catalyst-free tandem alkylation/decarboxylation reaction with conservation of the double bond.

A Regioselective Metal-Free Construction of 3-Aroyl Coumarins by Csp2-H Functionalization.

A successive metal-free TBHP-mediated regioselective C-H functionalization of coumarins toward expedient synthesis of 3-aroyl coumarins is unveiled. The ongoing method conducted through the reaction of either coumarins or coumarin-3-carboxylic acids with aromatic aldehydes. The optimized reaction condition also worked well with benzyl alcohols and styrenes as surrogates for aldehydes, which bear latent carbonyl functionality.

A biocompatible double network hydrogel based on poly (acrylic acid) grafted onto sodium alginate for doxorubicin hydrochloride anticancer drug release.

This study involved the synthesis of a new biocompatible slow-release hydrogel named poly (acrylic acid) grafted onto sodium alginate (poly (AA-g-SA)) double network hydrogel (DNH). The hydrogel was created by polymerization of acrylic acid grafted onto sodium alginate polysaccharide using crosslinkers N,N'-methylenebisacrylamide and calcium chloride via free radical polymerization. The water absorbency of the poly (AA-g-SA) double network hydrogel was improved by optimizing the quantities of ammonium persulfate initiator, pH-sensitive monomer of acrylic acid, and crosslinkers. Various analytical techniques including attenuated total reflection Fourier-transformed infrared (ATR-FTIR), X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), thermal gravimetric analysis (TGA), field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), atomic force microscopy (AFM), and Brunauer-Emmett-Teller specific surface area analysis (BET) were used to characterize the synthesized hydrogels. The swelling and on-off switching behaviors of the hydrogels were investigated in deionized (DI) water at different temperatures and pH values. The optimum poly (AA-g-SA) DNH was tested for in vitro release of a hydrophilic chemotherapeutic drug, doxorubicin hydrochloride (DOX). The eco-friendly hydrogel favorably optimized the DOX slow release owing to its swelling rate, high absorption and regeneration capabilities. The findings of this study may have significant implications for medical and scientific research.

Palladium-catalyzed decarboxylative cross-coupling reactions: a route for regioselective functionalization of coumarins.

A straightforward, regioselective, and step-economical ligand-free palladium-catalyzed decarboxylative functionalization of coumarin-3-carboxylic acids is devised. This protocol is compatible with a wide variety of electron-donating and -withdrawing substituents and allows for construction of various biologically important π-electron extended coumarins.

Base/Solvent Controlled Divergent Synthesis of Norbornane-Fused Dihydrophenanthrenes and Triphenylenes via Palladium Catalyst.

A base/solvent controlled divergent synthesis for the construction of polycyclic hydrocarbons has been developed. In this process, norbornene through a reagent role leads to the synthesis of norbornane-fused dihydrophenanthrenes, which are essential due to their biological activities. Amazingly, by switching solvent and base, the role of norbornene becomes limited to a mediator/catalyst; therefore, it is removed from the final scaffold, and triphenylenes are regioselectively synthesized. Additionally, by removing norbornene from the reaction conditions, a different path leading to synthesis of unsymmetrically substituted triphenylenes with exceptional regioselectivity is established. This reaction includes a rare domino decarboxylation/C-H activation/annulation in a chemo- and regioselective manner.

Syn- versus anti-carbopalladation of alkynes with organoborons: access to indoles symmetrically and unsymmetrically substituted on their 2,3-positions.

A palladium (II)-catalyzed borono-ortho-CH activation/amination cascade for the construction of two C-N bonds and one C-C bond in a single synthetic sequence is reported. This method proceeds through a formal syn-carbopalladation of alkynes with organoboron compounds, forming alkenyl palladium species, which are trapped by simple amines to provide highly substituted indoles. Remarkably, with an electron-rich arylboronic acid, the reaction proceeds through an unexpected anti-carbopalladation terminated by ortho-CH activation of diarylalkyne/amination reaction to provide an unsymmetrically substituted 2,3-diaryl indole instead. In the follow-up chemistry, we demonstrate that urea participates in this cascade to offer a variety of free NH-indoles.

Triethanolamine-mediated palladium-catalyzed regioselective C-2 direct arylation of free NH-pyrroles.

An atom-economical phosphane-free palladium-catalyzed direct C-2 arylation of unactivated free NH-pyrroles is devised. This method provides a straightforward route to a wide variety of substituted 2-aryl-1H-pyrroles from readily accessible starting materials. Iodoarenes bearing electron-withdrawing and electron-donating substituents are tolerated under the presented reaction conditions. The scope of the reaction is also expanded to N-aryl and -alkylpyrroles albeit in lower yields.

Assembly of Indole Cores through a Palladium-Catalyzed Metathesis of Ar-X σ-Bonds.

We describe the development of a new method for construction of highly substituted indole scaffolds through the strategic utilizing of the metathesis of Ar-X σ-bonds based on the dynamic nature of palladium-based oxidative addition/reductive elimination. A suitable and simple catalytic system has provided an appropriate platform for a productive ligand exchange and consecutive carbopalladation/C-H activation/amination of phosphine ligands with alkynes and aromatic/aliphatic amines for construction of structurally diverse indoles.

A novel one-step synthesis of imidazo[5,1-a]isoquinolines via a tandem Pd-catalyzed alkylation-direct arylation sequence.

A palladium-catalyzed/norbornene-mediated one-step synthesis of highly functionalized imidazoles via a sequential alkyl-aryl and aryl-heteroaryl bond formation is devised. This method provides an efficient route to a wide variety of substituted imidazo[5,1-a]isoquinolines from readily accessible N-bromoalkyl imidazoles and aryl iodides.

A Fast Track to Indoles and Annulated Indoles through ortho- vs ipso-Amination of Aryl Halides.

A complementary site selective ortho- vs ipso-amination of aryl halides using non-electrophilic amine sources for construction of indole scaffolds is reported. A palladium-catalyzed alkyne insertion/C-H activation/palladacycle amination via merger of three easily diversified components including iodoarenes, alkynes, and amines delivers indoles with different substitution patterns even in gram scales. By employing ortho-bromoanilines, a consecutive annulative π-extension of indoles proceeds to construct indolo[1,2-f]phenanthridine scaffolds via four C-C and C-N bond formations in one pot.

A transition-metal-free fast track to flavones and 3-arylcoumarins.

A highly regioselective and transition-metal free one-pot arylation of chromenones with arylboronic acids has been achieved employing K2S2O8. The procedure consists of a sequence of some reactions including an arylation/decarboxylation cascade and proceeds well in aqueous media to afford biologically interesting flavones and 3-arylcoumarins. This method exhibited excellent selectivity and functional group tolerance under mild conditions. The reaction also showed perfect efficacy for the preparation of styryl coumarins.

Direct, one-step synthesis of condensed heterocycles: a palladium-catalyzed coupling approach.

[reaction: see text] A palladium-catalyzed one-step synthesis of fused aromatic heterocycles from bifunctional bromoenoates or bromoalkyl indoles and iodoarenes is reported. This method provides an efficient route to a wide variety of substituted polycyclic aromatic and heteroaromatic compounds from readily accessible starting materials.

Palladium/norbornene chemistry: an unexpected route to methanocarbazole derivatives via three Csp3-Csp2/Csp3-N/Csp2-N bond formations in a single synthetic sequence.

A Catellani reaction terminated by palladacycle amination leading to methanocarbazoles is reported. The outcome is the formation of three different Csp(3)-Csp(2)/Csp(3)-N/Csp(2)-N bonds through a Heck reaction/C-H activation/double amination cascade in one process.

A one-pot domino C-H, C-C activation in coumarins: a fast track to 2,3-diaryl benzo[b]furans.

An approach to synthesize 2,3-diaryl benzo[b]furans using coumarins and aryl bromides is developed. This state-of-the-art strategy capitalizes on a palladium-catalyzed one-pot decarbonylative diarylation of coumarins, paving the way to achieve biologically interesting 2,3-diaryl benzo[b]furans.

Synthesis and anticholinergic activity of 4-hydroxycoumarin derivatives containing substituted benzyl-1,2,3-triazole moiety.

A series of 4-hydroxycoumarin-derived compounds 8a-p containing N-benzyl-1,2,3-triazole motif were designed as AChE inhibitors. The title compounds were obtained conveniently using multicomponent click reaction. The in vitro anticholinesterase evaluation of synthesized compounds against AChE and BuChE showed that some of them are potent and selective inhibitors of AChE. Among them, 2-chlorobenzyl derivative 8k showed the most potent activity against AChE (IC50  = 0.18 µm). Its activity was also superior to that of standard drug tacrine. The kinetic study and molecular docking simulation of the most potent compound 8k were also described.

Three-bond breaking of cyclic anhydrides: easy access to polyfunctionalized naphthalenes and phenanthrenes.

Benzannulation of phthalic anhydrides with alkynes to polyfunctionalized naphthalenes and phenanthrenes was confirmed to be straightforward using a palladium catalytic system. Sequential liberation of CO2 and CO occurred via oxidative decomposition of anhydride. In the case of 1,8-naphthalenedicarboxylic anhydrides, both aryls were encompassed in the annulation reaction to afford acenaphthylenes.