Pd-catalyzed Suzuki-Miyaura Research Articles

Precision Propargylic Substitution Reaction: Pd-Catalyzed Suzuki-Miyaura Coupling of Nonactivated Propargylamines with Boronic Acids.

Palladium-catalyzed Suzuki-Miyaura cross-coupling is an efficient approach for C-C bond construction. Here we report a deaminative Suzuki-Miyaura reaction to achieve chemo- and regioselectivity in the cross-coupling of nonactivated propargylamines with boronic acids, in which methyl propiolate is introduced to promote the cleavage of the C-N bond to form the C-C bond. This method features a wide range of substrates, good functional group tolerance, and ease of operation, providing an alternative approach to accessing valuable propargylated aromatic compounds.

Recent Advancements in Continuous-Flow Suzuki-Miyaura Coupling Utilizing Immobilized Molecular Palladium Complexes.

Immobilized Pd-catalyzed Suzuki-Miyaura coupling under continuous-flow conditions using a packed-bed reactor, representing an efficient, automated, practical, and safe technology compared to conventional batch-type reactions. The core objective of this study is the development of an active and durable catalyst. In contrast to supported Pd nanoparticles, the attachment of Pd complexes onto solid supports through well-defined coordination sites is considered a favorable approach for preparing highly dispersed and stabilized Pd species. These species can be directly employed in various flow reactions without the need for pre-treatment. This concept paper explores recent achievements involving the application of immobilized Pd complexes as precatalysts for continuous-flow Suzuki-Miyaura coupling. Our focus is to elucidate the significance of the designed catalyst structures in relation to their catalytic performance under flow conditions. Additionally, we highlight various reaction systems and catalyst packing methods, emphasizing their crucial roles in establishing a practical synthesis process.

A Synthesis of α-Alkyl Cycloenones by Pd-Catalyzed Suzuki-Miyaura Coupling with Cyclic Morita-Baylis-Hillman Adducts.

We herein disclose a Pd-catalyzed Suzuki-Miyaura coupling of cyclic Morita-Baylis-Hillman adducts with organoboronic acids under mild conditions, which allows for a rapid access to diverse α-alkyl substituted cycloenones. The advantage of this method resides in the employment of functionalized allyl alcohols as the unprecedented electrophilic partners in the absence of external activators.

Synthesis of Mono-, Di-, Tri-, and Tetra-cationic Pyridinium and Vinylpyridinium Modified [2.2]Paracyclophanes: Modular Receptors for Supramolecular Systems.

In this report, a new series of mono-, di-, tri-, and tetra-cationic pyridinium and vinyl pyridinium-modified [2.2]paracyclophanes as useful molecular tectons for supramolecular systems are described. Regioselective functionalization at specific positions, followed by resolution step and successive transformations through Pd-catalyzed Suzuki-Miyaura and Mizoroki-Heck cross-coupling chemistry furnish a series of modular PCP scaffolds. In our proof-of-concept study, on N-methylation, the PCPs bearing (cationic) pyridyl functionalities were demonstrated as useful molecular receptors in host-guest supramolecular assays. The PCPs on grafting with light-responsive azobenzene (-N=N-) functional core as side-groups impart photosensitivity that can be remotely transformed on irradiation, offering photo-controlled smart molecular functions. Furthermore, the symmetrical PCPs bearing bi-, and tetra-pyridyl functionalities at the peripheries have enormous potential to serve as ditopic and tetratopic 3D molecular tectons for engineering non-covalent supramolecular assemblies with new structural and functional attributes.

Pd-Catalyzed Suzuki-Miyaura Cross-Coupling Reaction in Glycerol Using KOH as Base and Glycerol-Triethanolamine Deep Eutectic Solvent under Inorganic Base‑Free Conditions

Glycerol and glycerol-triethanolamine deep eutectic solvent are both environmentally benign, cost-effective, and practical solvents for the Pd-catalyzed Suzuki-Miyaura cross-coupling of aryl halides with arylboronic acids. Utilizing KOH as base, the reaction in glycerol proceeded smoothly with low catalyst loadings (up to 0.5 mol% of PdCl2(PPh3)2) providing excellent yields (up to 99%) of the cross-coupling products, which can be readily extracted with hexane. However, the recyclability of the glycerol medium containing the catalyst is limited to a few cycles. Furthermore, it was explored the use of chlorodiphenylphosphine as a pre-ligand. Although glycerol phosphinite was not generated in situ, PPh2Cl proved to be an excellent pre-ligand, yielding the coupling product with a 98% yield. Compared to glycerol, glycerol-triethanolamine deep eutectic solvent (TEOA:G DES) proves to be a superior solvent for the cross-coupling reaction. In addition, the presence of amine group in the solvent allowed to obtain an inorganic base-free cross-coupling protocol. Aryl bromides and aryl boronic acids containing both electron releasing and attracting functional groups can be coupled without requiring the addition of any further base, affording the biphenyl products in moderate to good yields. The cross-coupling products can be easily isolated by extraction with hexane. Moreover, we observed the formation of triethanolamine phenylboronate during the reaction. The triethanolamine boronate was subsequently synthesized through the condensation of phenylboronic acid with triethanolamine and fully characterized. 11B nuclear magnetic resonance (NMR) spectroscopy confirmed the coordination of the nitrogen to the boron atom of the triethanolamine boronate.

Synthesis of Functionalized Hexahydrocarbazoles by Beckmann Elimination and Nucleophile-Intercepted Beckmann Fragmentation.

The Beckmann elimination and nucleophile-intercepted Beckmann fragmentation (NuBFr) of oximes starting from regioisomeric indolinyl bicyclic ketones lead to products that are subjected to further synthetic manipulations and ultimately result in the stereospecific formation of densely functionalized hexahydrocarbazoles. The Pd-catalyzed Suzuki-Miyaura cross-coupling reaction of a key alkenyl bromide intermediate with various boronic acids gives arylated products.

Enzymatic Peptide and Protein Bromination: The BromoTrp Tag.

Bio-orthogonal reactions for modification of proteins and unprotected peptides are of high value in chemical biology. The combination of enzymatic halogenation with transition metal-catalyzed cross-coupling provides a feasible approach for the modification of proteins and unprotected peptides. By a semirational protein engineering approach, variants of the tryptophan 6-halogenase Thal were identified that enable efficient bromination of peptides with a C-terminal tryptophan residue. The substrate scope was explored using di-, tri-, and tetrapeptide arrays, leading to the identification of an optimized peptide tag we named BromoTrp tag. This tag was introduced into three model proteins. Preparative scale post-translational bromination was possible with only a single cultivation and purification step using the brominating E. coli coexpression system Brocoli. Palladium-catalyzed Suzuki-Miyaura cross-coupling of the bromoarene was achieved with Pd nanoparticle catalysts at 37 °C, highlighting the rich potential of this strategy for bio-orthogonal functionalization and conjugation.

Doubly N-confused and ring-contracted [24]hexaphyrin Pd-complexes as stable antiaromatic N-confused expanded porphyrins

As isomers of the regular porphyrins, N-confused porphyrins have attracted extensive attention of chemists because of their unique chemical structures, chemical reactivities, and physical properties, which result in their promising applications in the fields of catalytic chemistry, biochemistry and material science. Typically, N-confused porphyrins are synthesized via acid catalyzed condensation and following oxidation during which lactams are often formed as the byproducts. Here we report doubly N-confused and ring-contracted [24]hexaphyrin(1.1.0.1.1.0) mono- and bis-Pd-complexes as stable antiaromatic N-confused expanded porphyrins, which are synthesized through Pd-catalyzed Suzuki-Miyaura coupling of 1,14-dibromotripyrrin. These macrocycles show a paratropic ring currents, an ill-defined Soret band, a red-shifted weak absorption tail, and a small HOMO-LUMO gap. NBS bromination of the bis Pd-complex give its mono- and dibromides regioselectively, which are effectively used to synthesize a [24]hexaphyrin dimer and a NiII porphyrin-[24]hexaphyrin-NiII porphyrin triad, respectively.

Acenaphthoimidazolylidene-Ligated Palladacycle Enabled Suzuki-Miyaura Cross-Coupling Employing Equimolar Organoboron for Tri-Ortho-Substituted Bi(hetero)aryls and Teraryls.

The Pd-catalyzed Suzuki-Miyaura cross-couplings (SMRs) are utilized as the most practical method to construct C-C bond, especial for biaryls. However, a major disadvantage of current protocols is the requirement of excess organoboron coupling partner (1.5-3.0 equiv.). Herein, a novel palladacyclic 1,3-bis(2,6-diisopropylphenyl)acenaphthoimidazol-2-ylidene (AnIPr) precatalyst possessing a chiral oxazoline was designed, which enabled a general protocol towards bulky tri-ortho-substituted biaryls, ternaphthalenes and diarylanthracenes via the Pd-catalyzed SMR employing equimolar organoborons and aryl bromides. A remarkable scope of substrates with various functional groups and heterocycles were well compatible with an adaptability to synthesize useful ligands.

A Convergent Synthesis of HPK1 Inhibitor GNE-6893 via Palladium-Catalyzed Functionalization of a Tetrasubstituted Isoquinoline

A scalable convergent synthesis of GNE-6893 (1) involving Pd-catalyzed Suzuki–Miyaura cross-coupling and C–N coupling as key steps is reported. The production of the final active pharmaceutical ingredient (API) was achieved in 33% overall yield and 98 A% HPLC purity by a one-pot process of global deprotection, pH adjustment, crystallization, and isolation. Green chemistry practices were implemented in the process development of GNE-6893 (1) by utilizing a biocatalytic resolution to produce (3R,4S)-4-methyltetrahydrofuran-3-ol and replacing toxic triphosgene with a safer alternative, disuccinimidyl carbonate (DSC), to construct the carbamate penultimate intermediate to API.

TXPhos: a highly stable and efficient ligand designed for ppm level Pd-catalyzed Suzuki–Miyaura coupling in water

TXPhos, a highly stable and efficient ligand designed for ppm level Pd catalyzed Suzuki–Miyaura coupling reactions under micellar conditions with a TOF up to 40 000 s−1.

Bulky, electron-rich, renewable: analogues of Beller's phosphine for cross-couplings.

In recent years, considerable progress has been made in the conversion of biomass into renewable chemicals, yet the range of value-added products that can be formed from biomass remains relatively small. Herein, we demonstrate that molecules available from biomass serve as viable starting materials for the synthesis of phosphine ligands, which can be used in homogeneous catalysis. Specifically, we prepared renewable analogues of Beller's ligand (di(1-adamantyl)-n-butylphosphine, cataCXium® A), which is widely used in homogeneous catalysis. Our new renewable phosphine ligands facilitate Pd-catalysed Suzuki-Miyaura, Stille, and Buchwald-Hartwig coupling reactions with high yields, and our catalytic results can be rationalized based on the stereoelectronic properties of the ligands. The new phosphine ligands generate catalytic systems that can be applied for the late-stage functionalization of commercial drugs.

Catalytic desymmetrization of the mechanical bond

In the October issue of Chem , Chong Tian, Ye Zhu, and co-workers describe a post-synthetic catalyst-controlled desymmetrization strategy for synthesizing mechanically planar chiral rotaxanes by relying on distal ionic interactions between a prochiral rotaxane and a novel anionic chiral phosphine ligand to trigger a desymmetrizing Pd-catalyzed Suzuki-Miyaura coupling. In the October issue of Chem , Chong Tian, Ye Zhu, and co-workers describe a post-synthetic catalyst-controlled desymmetrization strategy for synthesizing mechanically planar chiral rotaxanes by relying on distal ionic interactions between a prochiral rotaxane and a novel anionic chiral phosphine ligand to trigger a desymmetrizing Pd-catalyzed Suzuki-Miyaura coupling.

Mechanically planar chiral rotaxanes through catalytic desymmetrization

<h2>Summary</h2> Establishing mechanical chirality has remained a substantial synthetic hurdle despite the fast-growing applications of interlocked architectures in supramolecular chemistry. Here, we report the development of a catalyst-controlled desymmetrization strategy that decouples the creation of mechanically planar chirality and assembly of interlocked bonds. Employing a novel class of anionic chiral phosphine ligands, the Pd-catalyzed Suzuki-Miyaura reactions enable enantioselective access to various mechanically planar chiral rotaxanes. This study demonstrates that precise catalytic stereocontrol over mechanical chirality is achievable by engaging distal ionic substrate-catalyst interactions, despite the noncovalent nature of the interlocking stereogenic elements.

De Novo Diastereoselective Synthesis of 1-Hydroxyl Allogibberic Methyl Ester en Route to Diverse Bioactive Molecules.

The first de novo synthesis of 1-hydroxyl allogibberic methyl ester, en route to pharbinilic acid and other bioactive molecules, is accomplished in diastereoselective manner. Key reactions of the synthesis include a Pd-catalyzed Suzuki-Miyaura cross-coupling reaction, a Lewis acid-catalyzed reductive Prins cyclization reaction, and a SmI2-mediated transannular pinacol coupling reaction. The synthesis provides a new avenue to access diverse relevant bioactive molecules.

Recoverable low fluorine content palladium complex-catalyzed Suzuki-Miyaura and Sonogashira coupling reactions under thermomorphic mode

The reaction of [PdCl2(CH3CN)2] and bis-5,5'-(RfCH2OCH2)-2,2′-bpy (1), where Rf = n-C4F8H, in the presence of dichloromethane (CH2Cl2) resulted in the synthesis of low fluorine content Pd complex, [PdCl2 [5,5′-bis-(RfCH2OCH2)-2,2′-bpy] (2). The Pd-catalyzed Suzuki-Miyaura and Sonogashira coupling reactions of several aryl halides with their respective reagents were selected to demonstrate the feasibility of catalytic activity and recycling usage with 2 as the catalyst by using dibutyl ether (DBE) as the solvent at 140–145 °C under the thermomorphic mode. The Pd complex 2-catalyzed Suzuki-Miyaura reactions of different aryl iodides with phenylboronic acid derivatives have showed good recycling results though its activity was observed to decrease after the fifth cycle. Similarly, 2-catalyzed Sonogashira reactions of several aryl iodides with phenyl acetylene have also displayed good recycling results for a total of up to 8 cycles, with a high yield and TON. The electronic effect studies from substituents in both Suzuki-Miyaura and Sonogashira coupling reactions showed that electron withdrawing groups on the aryl iodide speed up the reaction rate. Furthermore, the catalytic activity of the Pd complex (2) showed a better result with the more reactive aryl iodide compared to the less reactive aryl bromide and chloride. To our knowledge, this is the first example of recoverable low fluorine content Pd-catalyzed Suzuki-Miyaura and Sonogashira reactions under the thermomorphic mode.

Assembly of Pyran-Fused Isoquinolines via Rhodium-Catalyzed Double Annulations of Methyl Benzimidates with Diazo Compounds

AbstractA variety of pyran-fused isoquinoline derivatives were prepared in moderate to good yields through the rhodium-catalyzed dual C–H functionalization/annulation of methyl benzimidates and diazo compounds. A one-pot procedure, broad substrate scope, diversified products, and mild reaction conditions make this transformation a powerful tool for the synthesis of fused heteroarenes. In addition, the synthetic application was extended by large-scale synthesis and late-stage functionalization via Pd-catalyzed Suzuki–Miyaura, Heck, and Sonogashira cross-coupling reactions. Furthermore, a photophysical survey reveals that the pyran-fused isoquinoline products exhibit fluorescence properties and show potential for exploring fluorescent material applications.

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki-Miyaura coupling reactions.

The photochromic norbornadiene/quadricyclane system is among the most promising candidates for molecular solar thermal (MOST) energy storage. As in this context there is still the need for new tailor-made derivatives, borylated norbornadienes were synthesized that may be used as versatile building blocks. Thus, the 4,4,5,5-tetramethyl-2-(bicyclo[2.2.1]heptadien-2-yl)-1,3,2-dioxaborolane was prepared and shown to be a suitable substrate for Pd-catalyzed Suzuki–Miyaura coupling reactions with selected haloarenes. It was demonstrated exemplarily that the novel monosubstituted 2-(1-naphthyl)norbornadiene, that is accessible through this route, is transformed to the corresponding quadricyclane upon irradiation, whereas the back reaction can be accomplished by thermal treatment.

Triazine-Based Conjugated Microporous Polymers With Different Linkage Units for Visible Light-Driven Hydrogen Evolution.

Conjugated microporous polymers (CMPs), as a kind of two-dimensional material, have attracted extensive attention due to their advantages in visible light–driven photocatalytic splitting of water for hydrogen evolution. However, improving the microstructure and electronic structure of the material to enhance their photocatalytic performance for hydrogen evolution remains a challenge. We designed and reported two analogous CMPs including CMP-1 and CMP-2 that contain triazine and dibenzothiophene-S,S-dioxide units, which were prepared by Pd-catalyzed Suzuki-Miyaura coupling reaction. The main difference of two CMPs is that the triazine units are connected to benzene unit (CMP-1) or thiophene unit (CMP-2). Both of the CMPs exhibit excellent light capture capability, and compared with CMP-2, CMP-1 has faster separation rates and lower recombination rates for the charge carriers (electron/hole), and then, a higher hydrogen evolution rate was obtained from water decomposition reaction. We find the H2 production rate of CMP-1 can be up to 9,698.53 μmol g−1h −1, which is about twice of that of CMP-2. This work suggests that molecular design is a potent method to optimize the photocatalytic performance toward hydrogen evolution of the CMPs.

Fluoroaromatic 2H-imidazole-based push-pull fluorophores: Synthesis, theoretical studies, and application opportunities as probes for sensing the pH in saliva

A series of novel push-pull fluorophores based on 2H-imidazole scaffold bearing perfluorophenyl substituent and extended electron-donating conjugating π-system were synthesized. In particular, the Pd-catalyzed Suzuki-Miyaura coupling reactions were exploited as a main synthetic strategy to modify 4-(4-bromophenyl)-2,2-dimethyl-5-(pentafluorophenyl)-2H-imidazole with various electron-donating functionalities. The comprehensive photophysical studies were carried out for the synthesized fluorophores, including the analysis of absorbance and emission spectra and determination of absolute quantum yields. The designed compounds were found to have a strong emission in the range of 470–610 nm depending on both the nature of solvent used and the structure of electron-donating group attached to the aryl moiety. The pH effect of the aqueous-organic mixture buffer solution on the fluorescent characteristics of the synthesized compounds was established and the deprotonation-induced “turn-on” pH sensing mechanism supported by DFT calculations was proposed for the first time. Particularly, the sequence of deprotonation was confirmed, and free energies for all N-protonated and N-proton-free forms were calculated. No toxic effect on the human embryonic kidney cells (HEK-293) at concentration of ≤512 μM was observed in vitro experiments. In addition, new opportunities for the practical application of these molecular ensembles were demonstrated in case of fluorometric determination of the pH both in model solutions and real saliva probes, with 3-(4-(2,2-dimethyl-5-(pentafluorophenyl)-2H-imidazole-4-yl)phenyl)-9-phenyl-9H-carbazole being used.