Ligand-free Conditions Research Articles

C−H Activation of Benzamides Using Biogenically Synthesized Pd@CNTs Catalyst under External Ligand Free Condition: Access to Isoquinolones and A DFT Study of Phytochemicals

AbstractEnvironmentally amiable biogenic strategy for in‐situ one‐step synthesis of Pd‐NPs decorated on carbon nanotubes (CNTs) and its synthetic utility for C−H activation of benzamides to access isoquinolones has been reported for the first time. The phytochemicals present in Gliricidia sepium leaves extract was found to be serve as a reducing agent to reduce Pd (II) to Pd (0) and subsequently acts as a stabilizing agent. The formation of Pd@CNTs was confirmed by P‐XRD, FE‐SEM, EDX and ICP‐OES analysis technique with active Pd content 42.82 % w/w. In addition, DFT study of phytochemicals found in Gliricidia sepium leaves extract were conducted. The catalytic activity was showcased for the cost‐effective, step and atom economic synthesis of isoquinolones via C−H and N−H bond activation without the aid of external ligands. A series of isoquinolone derivatives were synthesized in good to excellent yields under air as a sole oxidant. In addition, catalyst recyclability and mechanistic experiments were deliberated. The Pd@CNTs unveiled superior catalytic activity and high durability towards hydrogen evolution reaction in acidic media. The Pd@CNTs attains the current density of 10 mA/cm2 at an over potential of 127 mV with a small Tafel slope of 41 mV/dec.

A General Synthesis of Cross-Conjugated Enynones through Pd Catalyzed Sonogashira Coupling with Triazine Esters.

The palladium-catalyzed Sonogashira coupling of α, β-unsaturated acid derivatives offers a diversity-oriented synthetic strategy for cross-conjugated enynones. However, the susceptibility of the unsaturated C-C bonds adjacent to the carbonyl group toward Pd catalysts makes the direct conversion of α, β-unsaturated derivatives as acyl electrophiles to cross-conjugated ketones rare. This work presents a highly selective C-O activation approach to prepare cross-conjugated enynones using α, β-unsaturated triazine esters as acyl electrophiles. Under base and phosphine ligand-free conditions, NHC-Pd(II)-Allyl precatalyst alone catalyzed the cross-coupling of α, β-unsaturated triazine esters with terminal alkynes efficiently, yielding 31 cross-conjugated enynones with diverse functional groups. This method demonstrates the potential of triazine-mediated C-O activation for preparing highly functionalized ketones.

Copper catalyzed N-arylation of sulfonamides with aryl bromides under ligand-free conditions

A practical strategy for the C-N cross-coupling of both aliphatic and aromatic sulfonamides with a variety of substituted aryl bromides is reported. Under the optimized conditions, a good representative of N-arylated products were obtained in good to excellent yields (up to 78%) under the ligand-free conditions.

Copper-Mediated C4-Benzylations of 5-Aminopyrazoles with 3-Indoleacetic Acids

Herein, we present a copper-mediated C4-benzylation of 5-aminopyrazoles with 3-indoleacetic acids. Various benzylated 5-aminopyrazoles are prepared in good-to-excellent yields under basic and ligand-free conditions in the presence of copper acetate. Moreover, this benzylation method is applicable to other substrates, including naphthylamine, 2-aminochromen-4-one, and enamines. Some products exhibit antiproliferative activities against cancer cell lines. In addition, the C4-benzylated products are cyclized into 1H-pyrazolo[4',3':6,7]azepino[3,4-b]indoles with aldehydes via one-pot two-step processes; notably, the cyclized products exhibit fluorescence emissions with large Stokes shifts.

CuF2/MeOH-Catalyzed N3-Selective Chan-Lam Coupling of Hydantoins: Method and Mechanistic Insight.

An efficient and practical N-arylation of hydantoins with substituted aryl/heteroaryl boronic acids has been established, assisted by CuF2/MeOH under the base and ligand-free conditions at room temperature and open air. The protocol is general, and various N-arylated hydantoins have been prepared in excellent yields with exclusive regioselectivity. The CuF2/MeOH combination was explored further to furnish selective N3-arylation of 5-fluorouracil nucleosides. The efficiency of the protocol was also demonstrated with the gram-scale synthesis of the marketed drug, Nilutamide. A mechanistic study based on density functional theory calculations revealed that both hydantoin and MeOH are crucial for the generation of catalytically active copper species in the reaction process, in addition to their role as a reactant and solvent, respectively. The proposed reaction mechanism indicated that selective N3-arylation of hydantoin is favorable in MeOH, which helps initiate the catalytic cycle by forming a square-planner Cu(II) complex where strong hydrogen-bond interactions are observed. This study is expected to improve the understanding of Cu(II)-catalyzed oxidative N-arylation reactions and for the de novo design and development of Cu-catalyzed coupling reactions.

Palladium (II)-catalyzed C H bond functionalization of aromatic and heteroaromatic esters with acrylates under ligand-free conditions and their Anti-microbial evaluation

Palladium (II)-catalyzed C H bond functionalization of aromatic and heteroaromatic esters with acrylates under ligand-free conditions and their Anti-microbial evaluation

Palladium-Catalyzed C7–H (Hetero)arylation of Pyrazolo[1,5-a]pyrazines with Heteroarenes and Aryl Iodides with the Assistance of Silver Salts

AbstractPyrazolo[1,5-a]pyrazines coupled with heteroarenes and aryl iodides selectively at the C7 position to afford a broad library of bi(hetero)aryl structures under ligand-free palladium-catalyzed conditions. The key to the success of the reaction is the use of silver salts as the oxidant or the base, allowing the regioselective C–H bond functionalization to occur under relatively mild conditions.

An Efficient Recyclable Polymer Supported Palladium Catalyst for Suzuki Reaction in Water

AbstractThis work describes the development of an efficient and reusable heterogeneous polymer supported palladium catalyst for Suzuki reaction in water. This novel catalyst system was designed through monoethanolamine (MEA) modification of nitrile group in Polyacrylonitrile (PAN) followed by metal salt (PdCl2) complexation. The resulting polymer complex (mPAN‐Pd) was then successfully optimised as an efficient heterogeneous catalyst for Suzuki reaction under ligand free conditions. The supported catalyst provided excellent reactivity in the coupling reactions of a series of aryl halides with phenyl boronic acids under mild reaction condition. The reaction proceeded in presence of 2 mol % ofmPAN‐Pdcatalyst at 80 °C in water and the resulting products were isolated in moderate to excellent yields upto 98 %. Furthermore, this catalyst can be conveniently recovered by simple filtration and reused at least five times without an appreciable loss in its activity or Palladium leaching.

Chromium-Catalyzed syn-Selective Ring-Opening Aryl-/Alkylation of 7-Oxabenzonorbornadiene Derivatives with Grignard Reagents

Chromium(III) trichloride in combination with aryl/alkyl Grignard reagents under ligand-free conditions exhibited extremely high catalytic activity (turnover number of up to 2.4 × 104) toward the syn-selective ring-opening aryl/alkylation of 7-oxabenzonorbornadiene derivatives, producing syn-2-aryl/alkyl-1,2-dihydronaphthalen-1-ols in high yields. The superior catalytic activity of the chromium catalyst under the ring-opening arylation conditions enabled us to use unstable aryl Grignard reagents with esters and N-protecting groups synthesized from the corresponding aryl iodides and turbo-Grignard reagent. Control experiments to elucidate the reactivity of arylchromium species such as neutral triarylchromium(III) and anionic tetraarylchromate(III) suggested that in situ formed diarylchromate(I) from tetraarylchromate(III) served as the active species in this catalytic reaction. The magnetic susceptibility of the in situ generated chromium species from CrCl3(thf)3 and excess amounts of p-tolylmagnesium bromide was reasonable for the low-spin Cr(I) species (μ = 1.93 μB).

A Novel Palladium-Based Heterogeneous Catalyst for Tandem Annulation: A Strategy for Direct Synthesis of Acridones

AbstractIn order to develop an efficient, rapid, and modular cascade strategy for the direct synthesis of acridones, palladium supported on sulfated alumina and microwave activation are employed. Multifunctional heterogeneous palladium catalysts were prepared in order to carry out the sequential annulation via a Buchwald–Hartwig amination followed by an intramolecular annulation in a one-pot process. This new protocol represents the first report on a catalytic tandem synthesis of acridone derivatives from commercially available starting materials, under ligand-free conditions. The scope of the present methodology is extended to the generation of a library of functionalized acridones, showing high functional group compatibility, in moderate to excellent yields. The applicability of this novel transformation was demonstrated by the concise total synthesis of the natural product arborinine.

Dehydrogenative Synthesis of Quinolines and Quinazolines via Ligand-Free Cobalt-Catalyzed Cyclization of 2-Aminoaryl Alcohols with Ketones or Nitriles

We present a convenient and efficient protocol to synthesize quinolines and quinazolines in one pot under mild conditions. A variety of substituted quinolines were synthesized in good to excellent yields (up to 97% yield) from the dehydrogenative cyclizations of 2-aminoaryl alcohols and ketones catalyzed by readily available Co(OAc)2·4H2O. This cobalt catalytic system also showed high activity in the reactions of 2-aminobenzyl alcohols with nitriles, affording various quinazoline derivatives (up to 95% yield). The present protocol offers an environmentally benign approach for the synthesis of N-heterocycles by employing an earth-abundant cobalt salt under ligand-free conditions.

3-Alkyl-2-pyridyl Directing Group-Enabled C2 Selective C-H Silylation of Indoles and Pyrroles via an Iridium Catalyst.

An iridium-catalyzed, directing group-enabled site selective intra- and intermolecular silylation of indoles and pyrroles with hydrosilanes has been developed under ligand-free conditions. Fine-tuning of the removable 3-alkyl-2-pyridyl directing group was found to be crucial for achieving high yields for C2-silylated indole and pyrrole products. Moreover, the scalability was demonstrated, and further transformations of the silylation products were achieved.

Blue LED-Promoted Syntheses of Phosphorothioates and Phosphorodithioates.

An environmentally friendly and resourceful modular protocol for the synthesis of phosphorochalcogenoates, phosphorochalcogenothioates, and phosphinothioates under blue light-emitting diode irradiation is described. The blue LED-promoted P-S, P-Se, and P-Te bond constructions occurred under metal-free, ligand-free, oxidant-free, and photocatalyst-free conditions with minimum chemical waste generation and high atom economy providing the resulting phosphorochalcogenoates, phosphorochalcogenothioates, and phosphinothioates in good to excellent yields.

Copper(II)-Catalyzed 1,6-Hydroboration Reactions of p‑Quinone Methides Under Ligand-Free Conditions: A Sequential Methodology to gem-Disubstituted Methanols

Copper(II)-Catalyzed 1,6-Hydroboration Reactions of p‑Quinone Methides Under Ligand-Free Conditions: A Sequential Methodology to gem-Disubstituted Methanols

One-Pot Synthesis of 2,3-Disubstituted Indanone Derivatives in Water under Exogenous Ligand-Free and Mild Conditions

Diverse 2,3-substituted indanones are accessed in an efficient and robust protocol by a rhodium-catalyzed tandem carborhodium/cyclization and intramolecular proton shift pathway. The reaction is compatible with a broad range of functional internal acetylenes, especially for natural and functionalized alkynes derivatives, affording the desired indanones in good to excellent yields. Remarkably, this reaction features very mild and sustainable conditions using water as the sole solvent and without exogenous ligands. Control studies support that indanone is formed through the intramolecular proton transfer process from the key intermediate indenol.

Unconventional Site Selectivity in Palladium-Catalyzed Cross-Couplings of Dichloroheteroarenes under Ligand-Controlled and Ligand-Free Systems.

Halides adjacent to nitrogen are conventionally more reactive in Pd-catalyzed cross-couplings of dihalogenated N-heteroarenes. However, a very sterically hindered N-heterocyclic carbene ligand is shown to promote room-temperature cross-coupling at C4 of 2,4-dichloropyridines with high selectivity (∼10:1). This work represents the first highly selective method with a broad scope for C4-coupling of these substrates where selectivity is clearly under ligand control. Under the optimized conditions, diverse substituted 2,4-dichloropyridines and related compounds undergo cross-coupling to form C4-C(sp2) and C4-C(sp3) bonds using organoboron, -zinc, and -magnesium reagents. The synthetic utility of this method is highlighted in multistep syntheses that combine C4-selective cross-coupling with subsequent nucleophilic aromatic substitution reactions. The majority of the products herein (71%) have not been previously reported, emphasizing the ability of this methodology to open up underexplored chemical space. Remarkably, we find that ligand-free "Jeffery" conditions enhance the C4 selectivity of Suzuki coupling by an order of magnitude (>99:1). These ligand-free conditions enable the first C5-selective cross-couplings of 2,5-dichloropyridine and 2,5-dichloropyrimidine.

Synthesis of Phenolic Coumestans via a Sequential Dehydrogenation/Oxa-Michael Addition Reaction of 2',4'-Dihydroxyl-3-arylcoumarins.

A facile and practical approach for the synthesis of natural coumestans and derivatives starting from 2',4'-dihydroxyl-3-arylcoumarins has been developed. The process involved a seqential intramolecular dehydrogenation/oxa-Micheal reaction efficiently promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene at 40 °C under metal- and ligand-free conditions with good functional group compatibility.

Highly Efficient and Reusable Polymer Supported Palladium Catalyst for Copper Free Sonogashira Reaction in Water

AbstractDevelopment of a novel, greener and efficient heterogeneous catalytic system for copper free Sonogashira reaction in water is described. This novel catalyst can be easily prepared by a simple method through synthetic modification of nitrile group in Polyacrylonitrile (PAN) using monoethanolamine (MEA) followed by its complexation with palladium chloride (PdCl2). The resulting polymer Pd complex (mPAN‐Pd) was characterized by means of Fourier Transform Infrared Spectroscopy (FTIR), Energy‐Dispersive X‐ray Spectroscopy (EDAX), Inductively Coupled Mass Spectrometry (ICP‐MS) and X‐ray Photo Electron Spectroscopy (XPS) analyses. mPAN‐Pd was then explored as highly efficient heterogeneous catalyst for Sonogashira coupling reaction under copper and ligand free conditions in water affording the corresponding coupling products up to 97 % isolated yield. Moreover, the catalyst was recovered by simple filtration after the reaction and reused for next 5 cycles with excellent stability and activity. This is the first report on the use of ethanolamine modified PAN Pd (II) complex as an efficient heterogeneous catalyst for a coupling reaction.

Palladium‐Catalyzed Intramolecular C−H Heteroarylation to Access Fused Tricyclic Oxazolo[4,5‐c]Quinolines

AbstractSynthesis of fused tricyclic oxazolo[4,5‐c]quinolines from 2‐iodo‐N‐((2‐phenyloxazol‐4‐yl)methyl)anilines via intramolecular C−H heteroarylation in the presence of palladium catalyst under ligand free conditions has been disclosed. Various substituted 2‐iodo‐N‐((2‐phenyloxazol‐4‐yl)methyl)anilines are well tolerated and furnished the products in good yields. The synthetic utility of the resulting molecules has been demonstrated. This method features broad substrate scope, mild reaction conditions, good functional group tolerance, and scalability.

One-Pot Stereoselective Synthesis of 2,3-Diglycosylindoles and Tryptophan-C-glycosides via Palladium-Catalyzed C-H Glycosylation of Indole and Tryptophan.

We described a novel palladium-catalyzed C-H glycosylation of indole or tryptophan for a one-pot stereoselective synthesis of 2,3-diglycosylindoles and tryptophan-C-glycosides. In this strategy, the use of air and base-free and ligand-free conditions provided a highly efficient route to construct C-glycosides. The method can be applied to a wide range of cost-effective and convenient glycosyl chloride donors. Mechanistic studies indicated that the indole 2,3-diglycosylation sequence was C3 and then C2.