Palladium-catalyzed Coupling Research Articles

Incorporating Domain Knowledge and Structure-Based Descriptors for Machine Learning: A Case Study of Pd-Catalyzed Sonogashira Reactions.

Machine learning has revolutionized information processing for large datasets across various fields. However, its limited interpretability poses a significant challenge when applied to chemistry. In this study, we developed a set of simple molecular representations to capture the structural information of ligands in palladium-catalyzed Sonogashira coupling reactions of aryl bromides. Drawing inspiration from human understanding of catalytic cycles, we used a graph neural network to extract structural details of the phosphine ligand, a major contributor to the overall activation energy. We combined these simple molecular representations with an electronic descriptor of aryl bromide as inputs for a fully connected neural network unit. The results allowed us to predict rate constants and gain mechanistic insights into the rate-limiting oxidative addition process using a relatively small dataset. This study highlights the importance of incorporating domain knowledge in machine learning and presents an alternative approach to data analysis.

N-Heterocyclic Carbene-Palladium Polymers Network: Recyclable Pre-catalyst for Effective Suzuki-Miyaura Coupling Reaction in Water.

Rational design of high-efficiency N-heterocyclic carbene (NHC) palladium catalyst is of great importance to modern organic synthesis, especially in chemical and pharmaceutical industries. Herein, we fabricate a polymer network containing N-heterocyclic carbene palladium (PNNHC-Pd) catalytic active sites via an immobilization process. The N-heterocyclic carbene palladium can serve as a promising linkage of polymer network as well as an effective catalytic active site owing to its structural preference and strong σ-donating ability with palladium species. The results display that N-heterocyclic carbene palladium disperses homogeneously in polymer network, thus rendering PNNHC-Pd excellent catalytic activity, high stability and superior reusability in palladium-catalyzed Suzuki-Miyaura coupling reaction in aqueous medium. This work provides a new insight into the development of heterogenization of homogeneous catalysts based on polymer network.

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.

A practical total synthesis of wedelolactone

Wedelolactone, a benzofuran based natural product that can be isolated from Eclipta prostrata, exhibits a variety of biological activities. It is inefficient to obtain wedelolactone from natural sources, so it is of great significance to perform total synthesis study on this important compound. In the current study, a novel total synthesis of wedelolactone featuring palladium-catalyzed Suzuki coupling and acid-promoted intramolecular transesterification was discovered. In comparison with those reported total synthesis routes, the current strategy is more convenient and efficient, and can be used as a potential route for large scale production.

A highly efficient and selective fluorescent probe for Pd (II) based on benzotriazole-coumarin derivative and its catalytic application in Sonogashira reaction

Palladium-catalyzed coupling reactions have become effective tools for forming new carbon–carbon bonds. In this work, a novel fluorescence active benzotriazole-coumarin derivative, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-7-(diethylamino)-2-ox o-2H-chromene-3-carbohydrazide (BTANC), was synthesized as ligand in Pd(II) cation coordination. It is shown that BTANC has a strong fluorescent emission at 483 nm and Pd(II) can effectively quench the fluorescence of BTANC and BTANC shows excellent sensitivity and selectivity towards Pd (II) ions. Otherwise, the BTANC-Pd(II) complex was also tested in the Sonogashira coupling reaction of phenylacetylene and aryl halides. The desired product was obtained with high yield (up to 99%) under the optimized reaction conditions. More to that, Low fluorescence emission was observed during the Pd-catalyzed reaction process and the fluorescent emission of BTANC was recovered at the end of the Pd-catalyzed reaction because the oxidative addition of the aryl halide towards Pd (0) was shut down at the end of the Pd-catalyzed reaction. This fluorescence properties of BTANC indicates the feasibility of using fluorescence signal as a potential tool to monitor the completion of the Sonogashira coupling reaction.

Post-Modification of Pyrrolopyrrole Aza-BODIPY toward High Near-Infrared Fluorescence Brightness

Pyrrolopyrrole aza-BODIPYs (PPABs), dimeric aza-BODIPY analogues, exhibit intense absorption and fluorescence in the visible and near-infrared (NIR) regions. Here, we developed a facile postmodification by palladium-catalyzed coupling reactions to synthesize a series of donor-acceptor-donor (D-A-D) PPABs. Despite the possible fluorescence quenching dictated by the energy-gap low, D-A-D PPABs exhibit high-fluorescence brightness in the NIR region, implying their potential use as a bright NIR emitter.

Studies Towards The Synthesis of Tartrolons D and E

AbstractA concise and stereoselective synthesis of a key fragment C3-C22 unit of tartrolons D and E is demonstrated. Three crucial fragments are combined to form the 20-carbon chain, which contains four stereogenic centers in the monomeric unit of both natural products. The crucial fragments were synthesized in highly enantioselective routes from commercial starting compounds in two, eight, and two steps, respectively, and coupled using palladium-catalyzed Sonogashira coupling and directed 1,5-asymmetric aldol reaction as key steps.

An efficient construction of quinoline-based hybrid scaffolds through palladium-catalyzed C[sbnd]S coupling

Organosulfides have prodigious value and significance in synthetic and biological chemistry. In this context, an efficient and operationally simple constructionof quinoline based hybrid scaffolds has been achieved through palladium-catalyzed CS coupling synthetic strategy. This strategy employs the reaction of 2-(2-chloroquinolin-3-yl)-3-phenylthiazolidin-4-ones with thiophenols under palladium catalysis. Some notable features of this methodology like high efficiency, good functional group toleranceand easily obtainable substrates provides apromising platform. The employed strategyis anticipated to be further utilized in developing direct transformations of inert haloquinoline into synthesis of medicinally important building blocks.

Palladium-Catalyzed Oxidative Coupling of Dibenzosiloles with α-Diazo Esters: Formal Replacement of the Silyl Group with Carbenes

We report herein a Pd(II)-catalyzed oxidative coupling reaction of dibenzosiloles with aryl diazoacetates via a metal carbene migratory insertion process. In this reaction, carbenic carbon formally displaces silicon atoms through continuous cleavage of two C(sp2)–Si bonds and successive formation of two C(sp2)–C(sp3) bonds on a carbenic carbon. Density functional theory (DFT) studies reveal that the reaction proceeds through a Pd(II)/Pd(IV) catalytic cycle, in which the two C–Si bonds are cleaved by two successive oxidative addition/reductive elimination processes rather than traditional transmetalation steps. Additive o-chloranil was necessary for this reaction, which significantly facilitated the reaction by acting as both a ligand and an oxidant, and it played different roles in different reaction stages.

Synthesis, Photophysical properties and OFET application of thienothiophene and benzothiadiazole based Donor-π-Acceptor-π (D-π -A-π) type conjugated polymers

Novel conjugated donor- π -acceptor- π (D- π -A- π) type polymers (P1-P3), possessing thieno[3,2-b]thiophene (TT) with different aromatic substituents as donors, benzo[1–3]thiadiazole (BT) as an acceptor and thiophene as a π -linker, were designed and synthesized via palladium-catalyzed Stille coupling reaction. Their electronic, optical and thermal properties were investigated using UV–vis and fluorescence spectroscopies, cylic voltammetry, and thermal gravimetric analysis. Photophysical characterizations of these novel polymers showed a remarkable mega Stokes shift, reaching up to 130 nm and optic/electronic band gaps between 1.70 and 2.00 eV, as well as good thermal stability of degradation temperature at around 260 °C. To study the effect of electron donating and withdrawing groups on the electronic properties of the π -extended polymers, their organic field-effect transistors (OFETs) were fabricated and charge transport characteristics were investigated. While all three polymers showed a p-type field-effect behaviour, dimethylamine substituted P3 exhibited the highest average saturated hole mobility, μsat, 0.04 cm2 V−1 s−1, on/off current ratio, Ion/Ioff = 3.0 × 103, and the smallest subthreshold swing, SS, 250 mV dec-1, outperforming similar p-type D- π -A- π semiconducting polymers reported in the literature. The results presented in this work corroborate that the three novel TT-BT polymers have promising potential for electronic and optoelectronic applications, in particular where the tunability of field-effect behaviour is essential for performance.

A Team for Accelerating Catalyst and Reaction.

This invited Team Profile was created by the Gessner and Gooßen research groups at Ruhr-University Bochum (Germany). They recently published a series of articles in Angewandte Chemie on the application of ylide-substituted phosphines (YPhos) in palladium-catalyzed coupling reactions. Owing to their inherently strong sigma-donating ability and their modular synthesis, YPhos ligands can be tailored to fit the demands of various catalytic transformations. In the most recent article, machine learning methods were applied to identify a YPhos catalyst that enables the previously elusive Hiyama coupling of aryl chlorides. "Computer-Driven Development of Ylide Functionalized Phosphines for Palladium-Catalyzed Hiyama Couplings", J. F. Goebel, J. Löffler, Z. Zeng, J. Handelmann, A. Hermann, I. Rodstein, T. Gensch, V. H. Gessner, L. J. Gooßen, Angew. Chem. Int. Ed. 2023, e202216160; Angew. Chem. 2023, e202216160.

Synthesis of 5,6-Dihydrophenanthridines via Palladium-Catalyzed Intramolecular Dehydrogenative Coupling of Two Aryl C-H Bonds.

5,6-Dihydrophenanthridines are common aza heterocycle frameworks of natural products and pharmaceuticals. Herein, we reported the first palladium-catalyzed intramolecular C-H/C-H dehydrogenative coupling reaction of two simple arenes to generate 5,6-dihydrophenanthridines. The approach features a broad substrate scope and good tolerance of functional groups, offering an efficient alternative synthesis route for important 5,6-dihydrophenanthridine compounds.

Palladium-Catalyzed Unimolecular Fragment Coupling of N-Allylamides Bearing a Tethered Nucleophile with the Translocation of an Amide Group

AbstractThe palladium-catalyzed reaction of N-allylamides bearing a tethered nucleophile results in the extrusion of an amide moiety in the form of an isocyanate, with its subsequent capture by the pendant nucleophile­. This reaction involves the net catalytic transposition of an amide group.

A Simple, Transition Metal Catalyst-Free Method for the Design of Complex Organic Building Blocks Used to Construct Porous Metal-Organic Frameworks.

The design of metal-organic frameworks (MOFs) having large pore sizes and volumes often requires the use of complex organic ligands, currently synthesized using costly and time-consuming palladium-catalyzed coupling chemistry. Thus, in the present work, a new strategy for ligand design is reported, where piperazine and dihydrophenazine units are used as substitutes for benzene rings, which are the basic building block of most MOF ligands. This chemistry, which is based on simple, nucleophilic aromatic substitution (SN Ar) reactions, is used for the transition metal catalyst-free construction of 21 new, carboxylate-based ligands with varying sizes, shapes, and denticity and 15 linear di- and tetra-nitriles. Moreover, to demonstrate the utility of the ligands as building blocks, 16 new structurally diverse MOFs having surface areas up to 3100 m2 g-1 were also synthesized.

LARVICIDAL ACTIVITY OF THE SYNTHESISED LIGNANS, NEOLIGNANS, AND COUMARIN AGAINST Crocidolimia binotalis 2nd INSTAR LARVAE

Five compounds comprising 8-O-4’-neolignan (7), two arylnaphthalene lignans (5, 8), aryldihydrobenzofuran neolignan (4), and lignan (6) were synthesised by enzymatic coupling reaction using horseradish peroxidase (HRP) between vanillin (1) with methyl ferulate (2) or methyl sinapate (3). All of these compounds, as well as previously synthesised palladium-catalysed coupling products of neolignan (9), 8-O-4'-neolignan (10), arylcoumarin (11), and lignan (12), were examined for larvicidal activity against Crocidolomia binotalis 2nd instar larvae. It revealed that seven out of nine synthesised compounds had a mortality rate of more than 90% after 24 hours of exposure. Neolignan (10) and lignan (6) demonstrated the strongest larvicidal activity with LD50 = 2.218 mg/L and LD50 = 1.678 mg/L, respectively compared to the standard azadirachtin (LD50 =2.818 mg/L). The results showed that the synthesised compounds have a high potential for use in the control of C. binotalis larvae and could be used in the development of new and more effective compounds as larvicides.

Efficient Preparation of Chloroquine Enantiomers via Crystallization Resolution and Palladium-Catalysed Coupling

Abstract: Chloroquine (CQ) was found to exhibit antiviral activity against novel coronaviruses, which makes the preparation of CQ enantiomers particularly important. In this work, we developed an efficient method for the preparation of CQ enantiomers by crystallization resolution and palladium-catalyzed coupling. The obtained chiral CQ had been fully assigned by 1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC spectra. Moreover, the enantiomeric excess value of CQ was rapidly detected by binaphthol phosphate as a chiral NMR shift reagent.

Computer-Driven Development of Ylide Functionalized Phosphines for Palladium-Catalyzed Hiyama Couplings.

Palladium-catalyzed couplings of silicon enolates with aryl electrophiles are of great synthetic utility, but often limited to expensive bromide substrates. A comparative experimental study confirmed that none of the established ligand systems allows to couple inexpensive aryl chlorides with α-trimethylsilyl alkylnitriles. In contrast, ylide functionalized phosphines (YPhos) led to encouraging results. A statistical model was developed that correlates the reaction yields with ligand features. It was employed to predict catalyst structures with superior performance. With this cheminformatics approach, YPhos ligands were tailored specifically to the demands of Hiyama couplings. The newly synthesized ligands displayed record-setting activities, enabling the elusive coupling of aryl chlorides with α-trimethylsilyl alkyl nitriles. The preparative utility of the catalyst system was demonstrated by the synthesis of pharmaceutically meaningful α-aryl alkylnitriles, α-arylcarbonyls and biaryls.

Palladium-Catalyzed Cyclization Coupling with Cyclobutanone-Derived N-Tosylhydrazones: Synthesis of Benzofuran-3-Cyclobutylidenes and Spirocyclobutanes

A palladium-catalyzed cyclization coupling of iodoarene-tethered alkynes with cyclobutanone-derived N-tosylhydrazones is reported, providing a convenient and efficient approach to benzofuran-3-cyclobutylidenes. On this basis, spirocyclobutanes can be generated smoothly in an efficient cascade manner by the addition of dienophiles. Good yields and scalability are demonstrated. Sequential intramolecular carbopalladation, palladium-carbene migratory insertion, δ-hydride elimination, and cycloaddition processes are involved.

Palladium-Catalyzed Cross-Electrophile Coupling between Aryl Diazonium Salt and Aryl Iodide/Diaryliodonium Salt in H2O–EtOH

We report herein a mild highly chemoselective palladium-catalyzed cross-electrophile coupling between readily accessible aromatic diazonium salt and aryl iodide or diaryliodonium salt in water-ethanol (2:1) medium. Mechanistic studies revealed that ethanol is crucial to generate an active Pd(0) catalyst, and the counterion of the diazonium salt renders a cationic Pd(II) species that facilitates subsequent oxidative addition to aryl iodide/diaryliodonium salt. Silver(I) salt was crucial to retain the catalytic activity of palladium, removing the iodide ion as a precipitate.

Recent advances and prospects in palladium-catalyzed Hiyama coupling reaction

Recent advances and prospects in palladium-catalyzed Hiyama coupling reaction