Palladium-catalyzed Suzuki-Miyaura Coupling Research Articles

Palladium-Catalyzed Atroposelective Suzuki-Miyaura Coupling to Construct Axially Chiral Tetra-Substituted α-Boryl Styrenes.

Palladium-catalyzed Suzuki-Miyaura (SM) coupling is a valuable method for forming C─C bonds, including those between aryl moieties. However, achieving atroposelective synthesis of axially chiral styrenes via SM coupling remains challenging. In this study, a palladium-catalyzed atroposelective Suzuki-Miyaura coupling between gem-diborylalkenes and aryl halides is presented. Using the monophosphine ligand Me-BI-DIME (L2), a range of axially chiral tetra-substituted acyclic styrenes with high yields and excellent enantioselectivities are successfully synthesized. Control experiments reveal that the gem-diboryl group significantly influences the product enantioselectivities and the coupling prefers to occur at sites with lower steric hindrance. Additionally, the alkenyl boronate group in the products proves versatile, allowing for various transformations while maintaining high optical purities.

Synthesis of Chiral Biphenyl Monophosphines as Ligands in Enantioselective Suzuki-Miyaura Coupling.

Herein, we describe our design and synthesis of novel chiral monophosphine ligands by the short-step addition of chiral lactates as side chains to the well-known ligand SPhos/RuPhos. The new chiral ligands were shown to be highly efficient in palladium-catalyzed Suzuki-Miyaura coupling, providing a series of axially chiral biphenyl products in high yield and high enantioselectivity. Furthermore, the gram-scale reaction and the diverse conversions of the products demonstrated the potential utility of the approach.

Decarboxylative Iodination and Suzuki-Miyaura Coupling Reactions to Access Chiral 3,3'-Diaryl-1,1'-bi-2-naphthols.

An efficient synthesis of the enantiomerically pure 3,3'-bis-arylated BINOLs is accomplished through decarboxylative iodination of the dimethyl ether derivative of BINOL-3,3'-dicarboxylic acid followed by Suzuki-Miyaura coupling using a one-pot protocol. The decarboxylative iodination is effected with the dimethyl ether derivative of BINOL-3,3'-dicarboxylic acid using iodine as a terminal oxidant and the cheaply available K3PO4 as a base under neat conditions. This protocol facilitated the introduction of the aryl group at the 3,3'-position on the binaphthyl system using aryl boronic acid through a palladium-catalyzed Suzuki-Miyaura coupling reaction.

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.

Palladium-catalysed Suzuki-Miyaura coupling of α,β-unsaturated superactive triazine esters.

Palladium-catalysed Suzuki-Miyaura couplings of α,β-unsaturated acid derivatives are challenging due to the susceptibility of their CC bonds adjacent to carbonyl groups. In this work, we describe a highly selective C-O activation approach to this transformation using superactive triazine esters and organoborons as coupling partners. 42 α,β-unsaturated ketones with diverse functional groups have been prepared with this method. The mechanistic investigation unveiled that the dual function of triazine for activating the C-O bond and stabilizing non-covalent interactions between the catalyst and substrate is critical for the reaction's success. The method's efficiency, functional group compatibility and unique mechanism make it a valuable alternative to classic methods.

Regioselective coupling of benzyl chlorides with allyl and allenyl boronates catalysed by a bidentate phosphine ligand/palladium catalyst.

A palladium-catalysed aromative benzylic allylation and allenylation of benzyl chlorides with allyl and allenyl pinacolborates is described for the first time. The reactions proceed smoothly in the presence of a bidentate phosphine ligand to afford normal cross-coupling products in good yields. This novel synthetic procedure exhibits good tolerance for various electron-withdrawing and -donating functional groups linked to aromatic rings and is also well tolerant of sensitive functional groups such as NO2, CF3, CN, and COOMe. The utilisation of a bidentate ligand and heating are essential to transformation. The DFT calculation results reveal that wide-bite-angle bidentate ligands are beneficial to the formation of an η1-benzyl-η1-allylpalladium intermediate and that the normal coupling is thermodynamically favourable.

Hybrid Phosphine/Amino-Acid Ligands Built on Phenyl and Ferrocenyl Platforms: Application in the Suzuki Coupling of o-Dibromobenzene with Fluorophenylboronic Acid.

We describe the synthesis and characterization of two classes of hybrid phosphino ligands functionalized with amino ester or amino acid groups. These compounds are built either on a rigid planar phenyl platform or on a functionalized - conformationally controlled - rotational ferrocene backbone. Modifications at the -PR2 phosphino groups (R=aryl and alkyl, with various steric bulk, Ph, Mes, i-Pr, Cy) and at the amino acid/amino ester functions are reported, showing a valuable high modularity. The coordination chemistry of these compounds regarding palladium and gold was investigated, in particular with respect to the coordination mode of the phosphino groups and the preferred interaction with metals for the amino ester and amino acid functions. For all the hybrid ligands, based either on ferrocenyl or phenyl platforms, the (P,N)-chelating effect dominates in solution for coordination to Pd(II), while linear P-Au(I) complexes without interaction with the amino groups are assumed. The investigation of the catalytic activity of these new ligands in the demanding palladium-catalyzed Suzuki-Miyaura coupling of o-dibromoarenes with fluorophenylboronic acid underlined the importance of the amino ester dicyclohexylphosphinoferrocene for avoiding the deleterious homocoupling and arene oligomerization side-reactions that were otherwise observed with the other phosphine ligands.

Utilization of supercritical carbon dioxide as green solvent for the Suzuki-Miyaura reaction

Newly designed alkylated acetyl acetone ligands which are 3-n-butyl-2,4-pentanedione and 3-perfluorobutyl-2,4-pentanedione were prepared by alkylation of active methylene group of 2,4-pentanedione and then used as ligands for preparation of palladium (II) (Pd) complexes soluble in supercritical carbon dioxide deposition. The solubility of prepared palladium complexes was inclusively measured in supercritical carbon dioxide at varying pressures and temperatures. The results showed that solubility of the fluorinated complex is higher than the non-fluorinated complex. The solubility of Pd complex of 3-perfluorobutyl-2,4-pentandione [Pd(FBACAC)2] ranged between 4.51 g·L−1 and 8.66 g·L−1 while the solubility of Pd complex of 3-n-butyl-2,4-pentandione Pd(BACAC)2 varied from 0.21 g·L−1 to 1.1 g·L−1 at different temperature and pressures. Efficient Suzuki-Miyaura cross-coupling reaction catalytic system for novel catalysts was carried out at various temperatures and pressures. To the best of our knowledge, it is the first study without using co-solvent, ionic liquid and phase transfer catalyst for Suzuki-Miyaura CC coupling reaction in supercritical carbon dioxide catalyst system. The results demonstrated a successful application of novel alkylated acetylacetone for palladium-catalyzed Suzuki-Miyaura coupling reaction between a phenylboronic acid and bromobenzene in scCO2.

Pd Reaction Intermediates in Suzuki-Miyaura Cross-Coupling Characterized by Mass Spectrometry.

Palladium-catalyzed Suzuki-Miyaura (SM) coupling is widely utilized in the construction of carbon-carbon bonds. In this study, nanoelectrospray ionization mass spectrometry (nanoESI-MS) is applied to simultaneously monitor precatalysts, catalytic intermediates, reagents, and products of the SM cross-coupling reaction of 3-Br-5-Ph-pyridine and phenylboronic acid. A set of Pd cluster ions related to the monoligated Pd (0) active catalyst is detected, and its deconvoluted isotopic distribution reveals contributions from two neutral molecules. One is assigned to the generally accepted Pd(0) active catalyst, seen in MS as the protonated molecule, while the other is tentatively assigned to an oxidized catalyst which was found to increase as the reaction proceeds. Oxidative stress testing of a synthetic model catalyst 1,5-cyclooctadiene Pd XPhos (COD-Pd-XPhos) performed using FeCl3 supported this assignment. The formation and conversion of the oxidative addition intermediate during the catalytic cycle was monitored to provide information on the progress of the transmetalation step.

Micellar catalysis beyond the hydrophobic effect: Efficient palladium catalyzed Suzuki-Miyaura coupling of water and organic solvent insoluble pigments with food grade surfactants

Micellar catalysis is having a dramatic impact in improving the sustainability of a wide variety of chemical transformations, including most of the popular palladium mediated carbon–carbon and carbon–nitrogen bond forming reactions. The Suzuki-Miyaura coupling is one of the earliest examples of micellar catalyzed reactions and it is still a very much active research field even at industrial scale. So far, micellar catalysis proved particularly efficient in enabling the high yield, low catalyst loading and mild reaction condition coupling of hydrophobic reagents in a water solution of selected surfactants. In this paper we show that the use of aqueous solutions of a mixture of food grade lecithin and the industrial surfactant Tween 80 not only enables efficient coupling in water of hydrophobic chemicals, but also provides a very resourceful tool for the functionalization of water and organic solvent insoluble pigments of interest for the dye and printed electronic industries.

Synthesis and Biological Evaluation of Biphenyl Derivatives of Hydrazine via Palladium Catalyzed Suzuki-Miyaura Coupling Reaction

Generally, several methods for the construction of biphenyls, including Stille coupling, GombergBachmann reaction, Ullmann reaction and Suzuki-Miyaura cross-coupling are reported. In present research, considering the particularities of these methods and the characteristics of the target compounds by Suzuki-Miyaura cross-coupling reaction. To investigate the optimal conditions, a model reaction was performed using 1-bromo-4-iodobenzene and phenyl boronic acid under different conditions. The products were characterized by FT-IR, mass, 1H NMR and 13C NMR spectroscopy.

Synthesis and Optical Properties of Conjugated Copolymers based on Phenoxazine and Fluorene for an Activated Layer in Polymeric Solar Cell Applications

In this research, a conjugated copolymer based on phenoxazine and fluorene units was synthesized via palladium-catalyzed Suzuki–Miyaura coupling polymerization in the presence of a Pd catalyst and K2CO3 as the base. The number-average molecular weight of conjugated polymers was obtained to be approximately 2616 g/mol with a polydispersity index of 1.65. The yield of polymerization was established to be approximately 29%. The chemical structure, average molecular weights and optical properties of the conjugated polymer were characterized via proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared (FT-IR) spectroscopies, gel permeation chromatography (GPC), UV−vis and fluorescence spectroscopies. The conjugated polymer showed an optical band gap of 2.09 eV. The obtained conjugated polymers displayed fluorescence properties under an excitation wavelength of 400 nm. The conjugated polymers exhibit potential as activated layers in organic solar cells, proving the analysis results.

Arylketones as Aryl Donors in Palladium-Catalyzed Suzuki-Miyaura Couplings.

Herein, we report the arylation, alkylation, and alkenylation of aryl ketones via a palladium-catalyzed Suzuki-Miyaura cross-coupling reaction. The use of the pyridine-oxazoline ligand is the key to the cleavage of the unstrained C-C bond. The late-stage arylation of aryl ketones derived from drugs and natural products demonstrated the synthetic utility of this protocol.

Synthesis, characterization, molecular structure, and computational studies on 4(1H)-pyran-4-one and its derivatives

4(1H)-Pyridone-based compounds have shown promise as potent bioactive inhibitors against a broad range of diseases, particularly malaria. Our interest in 4(1H)-pyridones initiated the design and synthesis of a series of 4(1H)-pyridone derivatives, with the hope of finding new antimalarial leads. The synthesis of 4(1H)-pyran-4-one analogues (4(1H)-pyridone intermediates was successfully achieved using palladium catalyzed Suzuki-Miyaura coupling reactions. The synthesized 4(1H)-pyran-4-ones were unambiguously confirmed by TGA, 13C, 1H NMR, and IR spectroscopic analysis. Further comprehensive insights to rationalize the outcome of several reactions were deduced by means of single crystal X-ray diffraction, which was used to determine the single crystal structures of compounds 4 and 5. Compounds 5, 9 and 9a-e were successfully synthesized in moderate to excellent yields, apart from compound 9e which gave a very low yield. NMR and XRD analysis of the by-product of compound 9e showed that the boronic acid substituents reacted with each other in a side-reaction reminiscent to aryl boronic acid homo coupling or Ullmann coupling reactions. Complimentary DFT analysis of the pyranone and pyridone compounds provided insight into the substituent effect of the pyranone compounds with regards to the stability and lack of reactivity to form the corresponding pyridone compounds.

Tetracoordinate Boron Intermediates Enable Unconventional Transformations.

ConspectusOrganoboron compounds are a class of multifunctional reagents for the construction of carbon-carbon and carbon-heteroatom bonds in modern synthetic chemistry. The transformations of organoboron compounds are usually carried out through tetracoordinate boron intermediates and mainly include additions to unsaturated bonds, rearrangement reactions, transmetalation reactions, and so on. Although great progress has been achieved in improving tetracoordinate boron intermediates, there are still shortcomings, such as sparse activation modes, a paucity of reaction strategies and difficulties in stereoselective control. In this Account, we mainly discuss our recent advances in the development of unconventional transformations of organoboron compounds based on the design of tetracoordinate boron intermediates, including the following three topics: (1) the construction of C-B bonds; (2) the construction of C-C bonds; (3) the design and application of chiral tetracoordinate boron.The development of new strategies to build C-B bonds is of great interest for chemists. We have developed tandem reactions involving multiple tetracoordinate boron intermediates for the selective borylations of alkynes and the synthesis of stable tetracoordinate boron, including a domino-borylation-protodeboronation (DBP) strategy for selective borylations of alkynes, highly regio-, stereo-, and chemoselective Cu-catalyzed diborylation of β-CF3-1,3-enynes and cascade B-Cl/C-B cross-metathesis and C-H bond borylation for the synthesis of tetracoordinate triarylboranes. We have also developed novel strategies involving tetracoordinate boron intermediates to form C-C bonds because the formation of C-C bonds is an enduring theme of organic chemistry. We disclosed long distance or multiple migration reactions and novel coupling partners in transmetalation reactions, such as long distance 1,4-migrations of tetracoordinate nitrile oxide boron and nitrilium boron intermediates, multiple migrations of tetracoordinate isocyanide boron intermediate, palladium-catalyzed Suzuki-Miyaura coupling of thioureas or thioamides, copper-catalyzed atroposelective Michael-type addition, and a palladium-catalyzed atroposelective Catellani reaction. Moreover, in terms of stereoselective control of the tetracoordinate boron intermediate, we found that a chiral tricoordinate boron complex could activate water to form a chiral tetracoordinate boron complex with Brønsted acidity, which has been successfully applied with high enantioselectivity to the asymmetric catalytic reduction of challenging indoles.This Account summarizes our recent efforts using unconventional transformations of organoboron compounds for the design of tetracoordinate boron intermediates, which not only achieved the precise construction of a wide range of diverse C-B bonds and C-C bonds but also developed a novel chiral Brønsted acid for the asymmetric catalytic reduction of challenging indoles.

S(vi) in three-component sulfonamide synthesis: use of sulfuric chloride as a linchpin in palladium-catalyzed Suzuki-Miyaura coupling.

Sulfuric chloride is used as the source of the –SO2– group in a palladium-catalyzed three-component synthesis of sulfonamides. Suzuki–Miyaura coupling between the in situ generated sulfamoyl chlorides and boronic acids gives rise to diverse sulfonamides in moderate to high yields with excellent reaction selectivity. Although this transformation is not workable for primary amines or anilines, the results show high functional group tolerance. With the solving of the desulfonylation problem and utilization of cheap and easily accessible sulfuric chloride as the source of sulfur dioxide, redox-neutral three-component synthesis of sulfonamides is first achieved.

Synthesis and characterization of porphyrin–pyrene hybrids

Palladium-catalyzed Suzuki–Miyaura coupling of 5-functionalized Ni(II) porphyrins with 1,3,6,8-tetrafunctionalizedpyrenes was carried out to obtain two kinds of porphyrin–pyrene hybrids. These compounds were comprehensively characterized by nuclear magnetic resonance (NMR), high-resolution mass spectrometry and ultraviolet-visible (UV-vis) absorption spectrometry, and their electrochemical properties were studied by both cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Fluorescence spectra for zinc compounds and free-base compounds were performed. In addition, the structure of 4Zn, a porphyrin tetramer, was determined by X-ray diffraction analysis, in which two planes formed by the porphyrin unit and the pyrene moiety adopt nearly perpendicular geometry with two sets of dihedral angles displaying 85.14 (4)[Formula: see text] and 83.90 (4)[Formula: see text], respectively. In the UV-vis absorption spectra, the maximum wavelengths of Soret bands and Q bands for these hybrids were observed at 434 and 648 nm. As the number of porphyrin units increases, the corresponding molar extinction coefficient rises markedly, in which the maximal value is 7.4 × 105 M[Formula: see text] • cm[Formula: see text] belonging to 4Zn. Moreover, the presence of energy transformation from the pyrene moiety to the porphyrin unit has been proved by emission spectra. Finally, the electrochemical properties of these porphyrin–pyrene hybrids were analyzed by using cyclic voltammetry and differential pulse voltammetry, which show that the nickel hybrids possessed the maximal electrochemical highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap and the zinc compounds displayed the minimum electrochemical HOMO–LUMO gap.

A Scalable Synthesis of Biaryl Unit of the HIV Protease Inhibitor Atazanavir

Atazanavir is one of the most prescribed HIV-1 protease inhibitors approved by the FDA. It was the first protease inhibitor approved for once-a-day dosing to treat AIDS due to good oral bioavailability and favorable pharmacokinetic profile. This research aims to develop a new synthetic cost effective process for biaryl-hydrazine unit {tert-butyl 2-[4-(2-pyridinyl)benzyl]hydrazinecarboxylate} of atazanavir on a large scale. The synthesis involved palladium catalyzed Suzuki-Miyaura coupling of 2-chloropyridine and (4-cyanophenyl)boronic acid followed by DIBAL-H reduction of cyano group to aldehyde which is then treated with tert-butyl carbazate to furnish hydrazone subsequently in situ reduction with NaBH4. A large scale synthesis of biaryl-hydrazine unit of atazanavir was accomplished in three steps with 71% overall yield. We have developed a short and efficient synthesis of atazanavir key intermediate biaryl-hydrazine unit. The process does not require the usage of Grignard reagent, expensive catalyst, protection/deprotection of aldehyde moiety and catalytic hydrogenation.

Cover Feature: Original Suzuki–Miyaura Coupling Using Nitro Derivatives for the Synthesis of Perylenediimide‐Based Multimers (Eur. J. Org. Chem. 47/2019)

The Cover Feature shows 1-nitro-perylen-ediimide (1-nitroPDI), an attractive starting material for the preparation of “satellite-shaped” PDI-based multimers. The nitro derivative is involved as an original electrophile into efficient palladium-catalyzed Suzuki–Miyaura couplings with polyboronic ester linkers affording multimers of various geometries. The protocol improves the synthetic access to the reported class of tridimensional PDI based multimers, which are of particular interest as Non-Fullerene Acceptors in organic photovoltaics. More information can be found in the Full Paper by L. Rocard, P. Hudhomme et al.

Palladium-catalyzed Suzuki-Miyaura coupling of thioureas or thioamides

Cross-coupling reactions involving metal carbene intermediates play an increasingly important role in C–C bond formation. Expanding the carbene precursors to a broader range of starting materials and more diverse products is an ongoing challenge in synthetic organic chemistry. Herein, we report a Suzuki-Miyaura coupling reaction of in situ-generated Pd–carbene complexes via desulfurization of thioureas or thioamides. This strategy enables the preparation of a broad array of substituted amidinium salts and unsymmetrical diaryl ketones. The reaction is readily scalable, compatible with bromo groups on aromatic rings, tolerant to moisture and air and has a broad substrate scope. Furthermore, a single crystal structure of Pd-diaminocarbene complex is obtained and proven to be the key intermediate in both catalytic and stoichiometric reactions. Preliminary mechanistic studies demonstrate the dual role of the silver salt as a desulfurating reagent assisting the elimination of sulfur and as oxidant facilitating the PdII/Pd0/PdII catalytic cycle.