Search Results (19)

Tetrahydrofuran scaffolds have found promising applications in both pharmaceutical chemistry and organic synthesis but remain underexplored owing to the challenges associated with their preparation. Herein, we have developed a robust synthetic strategy for the palladium-catalyzed cascade annulation reaction of buta-1,3-dienes with alkynols for the assembly of diverse 3-methylenetetrahydrofurans with excellent functional group compatibility and good regioselectivity. More importantly, this protocol features broad substrate scope, good functional group tolerance, and good step- and atom-economy. A diverse array of functional groups such as halogen atoms, aldehyde, nitro, ester, and several aromatic heterocycles were also nicely tolerated and provided the corresponding products in moderate to good yields. It is noteworthy that the practicability is further verified by gram-scale experiments and synthetic transformation to access organic functional molecules. Full article

A synthesis of substituted 1,4-benzodiazepines has been developed via palladium-catalyzed cyclization of N-tosyl-disubstituted 2-aminobenzylamines with propargylic carbonates. The reaction proceeds through the formation of π-allylpalladium intermediates, which undergo intramolecular nucleophilic attack by the amide nitrogen to afford seven-membered benzodiazepine cores. In reactions involving unsymmetrical diaryl-substituted carbonates, regioselectivity was observed to favor nucleophilic attack at the alkyne terminus substituted with the more electron-rich aryl group, suggesting that electronic effects play a key role in determining product distribution. The versatility of this reaction was further demonstrated by constructing a benzodiazepine framework found in bioactive molecules, indicating its potential utility in medicinal chemistry. Mechanistic insights supported by stereochemical outcomes and X-ray crystallographic analysis of key intermediates reinforce the proposed reaction pathway. This palladium-catalyzed protocol thus offers an efficient and practical approach to access structurally diverse benzodiazepine derivatives. Full article

The polymerization mechanism of para-methoxystyrene catalyzed by cationic α-diimine palladium complexes with various ancillary ligands was rigorously examined using density functional theory. In the classical methyl-based α-diimine palladium complex [{(2,6-ⁱPr₂C₆H₃)-N=C(Me)-C(Me)=N-2,6-ⁱPr₂C₆H₃)}PdMe]⁺ (A⁺), the 2,1-insertion of para-methoxystyrene is favored over the 1,2-insertion, both thermodynamically and kinetically, during the chain initiation step. The resulting thermodynamically favored η³-π-benzyl intermediates face a substantial energy barrier, yielding only trace amounts of polymer, as experimentally verified. In contrast, the dibenzobarrelene-based α-diimine palladium complex [{(2,6-ⁱPr₂C₆H₃)-N=C(R)-C(R)=N-2,6-ⁱPr₂C₆H₃)}PdMe]⁺ (R = dibenzobarrelene, B⁺) shows similar energy barriers for both 2,1- and 1,2-insertions. Continuous 2,1/2,1 or 2,1/1,2 insertions are impeded by excessive energy barriers. However, theoretical calculations reveal that the 1,2-insertion product can seamlessly transition into the chain propagation stage, producing a polymer with high 1,2-regioselectivity. The observed activity of complexes A⁺ or B⁺ towards para-methoxystyrene polymerization stems from the energy barrier differences between the 1,2- and 2,1-insertions, influenced by the steric hindrance from the ancillary ligands. Further investigation into the effects of steric hindrance on the chain initiation stage involved computational modeling of analogous complexes with increased steric bulk. These studies established a direct correlation between the energy barrier difference ∆∆G (1,2–2,1) and the van der Waals volume of the ancillary ligand. Larger van der Waals volumes correspond to reduced energy barrier differences, thus enhancing the regioselectivity for para-methoxystyrene polymerization. Moreover, the experimental inertness of complex B⁺ towards styrene polymerization is attributed to the formation of stable kinetic and thermodynamic 2,1-insertion intermediates, which obstruct further styrene monomer insertion due to an extremely high reactive energy barrier. These findings contribute to a deeper understanding of the mechanistic aspects and offer insights for designing new transition metal catalysts for the polymerization of para-alkoxystyrenes. Full article

C-H activation is a powerful strategy for forming C-C bonds without the need for prefunctionalization. In this paper, we present a general, direct, and regioselective palladium-catalyzed functionalization of a phosphorus heterocycle, 2-phenyl-1H-isophosphinoline 2-oxide. The mild reaction conditions enabled the introduction of various functionalized alkenes. Moreover, the flame-retardant properties of selected products clearly highlighted the synergy between the phosphine oxide and another heteroatom-based group, even in the condensed phase. Full article

We reported palladium-catalyzed regioselective [3+2] cycloadditions of α,β-unsaturated imines with vinylethylene carbonates, providing the desired oxazolidines in moderate-to-high yields. This reaction provides a facile route for the highly regioselective synthesis of functional oxazolidines. The synthetic utility of the current method was also demonstrated by a gram-scale reaction. Full article

Dopamine is a key neurotransmitter involved in a series of biologically relevant processes and its derivatives have sparked significant interest as intriguing synthetic targets. This class of compounds is indeed not only considerable for the potential biological activities but is also promising for diverse applications in material science. In light of this, our research was focused on the synthesis of 6-aryldopamine derivatives starting from 4-(2-aminoethyl)phenol through a sequential protocol, whose main steps are hydroxylation, halogenation, and Suzuki cross-coupling. Our method demonstrated versatility, efficiency, and compatibility with various functional groups, including aldehydes, ketones, esters, ethers, and fluorine. Full article

A significant issue in developing metal-catalyzed plastic polymer materials is obtaining distinctive catalytic characteristics to compete with current plastics in industrial commodities. We performed first-principle DFT calculations on the key insertion steps for industrially important monomers, vinyl fluoride (VF) and 3,3,3-trifluoropropene (TFP), to explain how the ligand substitution patterns affect the complex’s polymerization behaviors. Our results indicate that the favorable 2,1-insertion of TFP is caused by less deformation in the catalyst moiety of the complexes in contrast to the 1,2-insertion mode. In contrast to the VF monomer, the additional interaction between the fluorine atoms of 3,3,3-trifluoropropene and the carbons of the catalyst ligands also contributed to favor the 2,1-insertion. It was found that the regioselectivity of the monomer was predominated by the progressive alteration of the catalytic geometry caused by small dihedral angles that were developed after the ligand–monomer interaction. Based on the distribution of the 1,2- and 2,1-insertion products, the activity and selectivity were influenced by the steric environment surrounding the palladium center; thus, an increased steric bulk visibly improved the selectivity of the bulkier polar monomer (TFP) during the copolymerization mechanism. In contrast, better activity was maintained through a sterically less hindered Pd metal center; the calculated moderate energy barriers showed that a catalyst with less steric hindrance might provide an opportunity for a wide range of prospective industrial applications. Full article

The catalytic activity and selectivity of two different water-soluble palladium nanoparticles capped with 5-(trimethylammonio)pentanethiolate and 6-(carboxylate)hexanethiolate ligands are investigated using the catalytic reaction of allyl benzene. The results show that the regioselective transformation of allyl benzene to 3-phenylpropanal occurs at room temperature and under atmospheric pressure in neat water via a Tsuji–Wacker type oxidation. Conventionally, the Tsuji–Wacker oxidation promotes the Markovnikov oxidation of terminal alkenes to their respective ketones in the presence of dioxygen. Water-soluble Pd nanoparticles, however, catalyze the anti-Markovnikov oxidation of allyl benzene to 3-phenylpropanal in up to 83% yields. Catalytic results of other aromatic alkenes suggest that the presence of benzylic hydrogen is a key to the formation of a p-allyl Pd intermediate and the anti-Markovnikov addition of H₂O. The subsequent b-H elimination and tautomerization contribute to the formation of aldehyde products. Water-soluble Pd nanoparticles are characterized using nuclear magnetic resonance (NMR), UV–vis spectroscopy, thermogravimetric analysis (TGA), and transmission electron microscopy (TEM). Catalysis results are examined using ¹H NMR and/or GC-MS analyses of isolated reaction mixtures. Full article

Nitrogen-containing heterocycles can have several applications in the pharmaceutical industry since they contain a wide spectrum of biological activities. Imidazolidinones have shown activity against leukemia, lung cancer, and metabolic disorders. These cyclic urea frameworks can be obtained through transition-metal-catalyzed intermolecular cycloaddition using an aziridine moiety as the starting material. These reactions often provide effective one-step procedures that result in heterocyclic derivatives that are challenging to access through conventional approaches. We have previously described the photoreaction of butyl pyridinium salt with the corresponding bicyclic aziridine in continuous flow. Additionally, we reported that the palladium-catalyzed ring opening of bicyclic aziridines with active methylenes exhibited a new S_N2’ selectivity. In this study, the reaction between bicyclic aziridines and several isocyanates, in the presence of Pd(0)-catalyst is presented. The reactions proceed through ring opening of the aziridine moiety, with the formation of the π-allylpalladium complex, followed by cyclization via nucleophilic addition of nitrogen to the isocyanate, affording regioselectively imidazolidinones. Full article

The first access to N-1, N-4 disubstituted pyrrolo[2,3-d][1,2,3]triazoles is reported. The series were generated using a “one-pot” MCR, leading to a single regioisomer of the attempted heteroaromatic skeleton in good yields. Next, the functionalization of C-5 and C-6 positions was investigated. (Het)aryl groups were introduced at the C-5 and C-6 positions of the pyrrolo[2,3-d][1,2,3]triazoles using regioselective electrophilic brominations followed by Suzuki–Miyaura cross coupling reactions. Palladium-catalyzed cross-coupling conditions were optimized and a representative library of various boronic acids was employed to establish the scope and limitations of the method. Full article

Indole moiety is well-known as a superlative framework in many natural products and synthetic pharmaceuticals. Herein, we report an efficient procedure to synthesize a series of functionalized 2-methyl-1H-indole-3-carboxylate derivatives from commercially available anilines properly functionalized by different electron-withdrawing and -donating groups through a palladium-catalyzed intramolecular oxidative coupling. The conversion of a variety of enamines into the relevant indole was optimized by exposing the neat mixture of reactants to microwave irradiation, obtaining the desired products in excellent yields and high regioselectivity. The synthesized compounds were confirmed by ¹H and ¹³C spectroscopic means as well as by high-resolution mass spectrometry. Full article

An efficient synthesis of ketimines was achieved through a regioselective Hg(I)-catalyzed hydroamination of terminal acetylenes in the presence of anilines. The Pd(II)-catalyzed cyclization of these imines into the 2-substituted indoles was satisfactorily carried out by a C-H activation. In a single-step approach, a variety of 2-substituted indoles were also generated via a Hg(I)/Pd(II)-catalyzed, one-pot, two-step process, starting from anilines and terminal acetylenes. The arylacetylenes proved to be more effective than the alkyl derivatives. Full article

Suzuki coupling reaction has been often used for the preparation of a diverse set of substituted pyrimidines. In this study, the Suzuki coupling of 2,4-dichloropyrimidines with aryl and heteroaryl boronic acids was investigated. A thorough screening of reaction conditions and the use of microwave irradiation led to a very efficient and straightforward synthetic procedure providing C4-substituted pyrimidines in good to excellent yields. Short reaction time (15 min) and extremely low catalyst loading (0.5 mol%) are the main advantages of our tetrakis(triphenylphosphine)palladium(0) catalyzed microwave-assisted procedure, which could be used for quick and low-cost regioselective preparation of substituted pyrimidine rings. Full article

Herein, an eco-friendly palladium-catalyzed tandem reaction for the one-pot synthesis of carbazoles under microwave irradiation is reported. This approach involves an amination and a direct arylation from available and inexpensive anilines and 1,2-dihaloarenes. For the development of this purpose, a novel recoverable palladium nanocatalyst supported on a green biochar under ligand-free conditions is used. Compared with other existing palladium-based protocols, the present synthetic methodology shows a drastic reduction in reaction times and excellent compatibility with different functional groups, allowing to obtain a small library of carbazoles with high yields and regioselectivity. The novel heterogeneous palladium nanocatalyst can be recycled and reused up to five times without significant loss activity. Full article

A flexible two-step, one-pot procedure was developed to synthesize 2-aryl propionic acids including the anti-inflammatory drugs naproxen and flurbiprofen. Optimal results were obtained in the presence of the novel ligand neoisopinocampheyldiphenylphosphine (NISPCPP) (9) which enabled the efficient sequential palladium-catalyzed Heck coupling of aryl bromides with ethylene and hydroxycarbonylation of the resulting styrenes to 2-aryl propionic acids. This cascade transformation leads with high regioselectivity to the desired products in good yields and avoids the need for additional purification steps. Full article