Cross-coupling Of Arylboronic Acids Research Articles

Microwave-Assisted Palladium Acetate-Catalyzed C-P Cross-Coupling of Arylboronic Acids and >P(O)H Reagents in the Absence of the Usual Mono- and Bidentate P-Ligands: Mechanistic Insights.

A less-studied halogen-free variation of the Hirao reaction involving the coupling of arylboronic acids with >P(O)H reagents, such as diarylphosphine oxides, diethyl phosphite, and ethyl phenyl-H-phosphinate, was investigated in detail using Pd(OAc)2 as the catalyst precursor and applying some excess of the P-reagent to supply the ligand via its trivalent tautomeric (>P-OH) form. The optimum conditions (1.2 equiv of the P-reagent, 135-150 °C, and air) were explored for the synthesis of diaryl-phenylphosphine oxides, aryl-diphenylphosphine oxides, diethyl arylphosphonates, ethyl diphenylphosphinate, and two bisphosphinoyl derivatives. In the reaction of 4-chlorophenyl- or 3-chlorophenylboronic acid with Ph2P(O)H, triphenylphosphine oxide was also formed as a byproduct. Theoretical calculations suggested that the catalytic cycle of the P-C coupling of PhB(OH)2 with Ph2P(O)H is different from that of the usual cross-coupling reactions. It comprises the addition of a phenyl anion and then the tautomeric form >P-OH of the >P(O)H reagent to the Pd2+ catalyst complex. This is then followed by reductive elimination affording Ph3PO that is accompanied with the conversion of Pd2+ to Pd0. There is a need for a subsequent stoichiometric oxidation of Pd(0) by molecular oxygen. The spontaneous formation of the self-assembling ligands around the Pd2+ center from the >P(O)H reactant plays a crucial role in the mechanism and promotes the efficiency of the catalyst.

Magnetically separable mixed metal oxide nanocomposite (Pd/MnFe2O4) for Suzuki cross-coupling in aqueous medium

Magnetically separable Pd/MnFe2O4 nanocomposite has been synthesized by coupling palladium with MnFe2O4via citrate gel auto combustion and deposition precipitation method. The physicochemical and microscopic study of Pd/MnFe2O4 was investigated using various characterization techniques. The zeta potential of the prepared nanocomposite Pd/MnFe2O4 was found to be highly negative value of -36.7 mV, which stabilizes the particle in its dispersed state and also helps to polarize the aryl-halide bond. The catalytic activity of Pd/MnFe2O4 was explored for Suzuki cross-coupling of aryl boronic acids and aryl halides (I, Cl, Br) in an aqueous medium. Interestingly, the rate of the slow oxidative addition step of the reaction is enhanced due to the high negative surface charge of the catalyst. It is worth mentioning that high turnover number (TON) and turnover frequency (TOF), thermal stability, ease of handling, nontoxic, magnetically separable, and recyclable are the remarkable properties of the present catalyst. Moreover, the protocol was found to be significant with respect to reaction time, substrate scope, the yield of products, and solvent used for the reaction.

Copper-Catalyzed, Ceric Ammonium Nitrate Mediated N-Arylation of Amines.

Cu-Catalyzed, ligand and base free cross-coupling of aryl boronic acids with primary and secondary amines has been reported. This 'Chan-Evans-Lam' reaction has revealed that at room temperature, catalytic copper(II) acetate and ceric ammonium nitrate (CAN) as an oxidant, N-arylation can result in an effective C-N bond formation. This air stable, practical, robust protocol enables a variety of functional group tolerance on both boronic acid and amine partners.

C-Se cross-coupling of arylboronic acids and diphenyldiselenides over non precious transition metal (Fe, Cu and Ni) complexes

Various tetradentate and tridentate ligands such as salophane, bishydrazone, bisbenzimidazolyl pyridine and isonicotinohydrazide have been prepared. Transition metal complexes of these ligands with Cu, Ni and Fe have been further synthesized and characterized by UV–vis, IR, NMR and CHN analysis. Catalytic activity of the metal complexes was tested for the cross coupling of diarylchalcogenide with arylboronic acid in DMSO as solvent in presence of a base. These non-precious metal complexes catalysed cross coupling reactions smoothly in shorter reaction time compared to earlier reports with comparable yields.

Copper-Catalyzed Oxidative Perfluoroalkylation of Aryl Boronic Acids Using Perfluoroalkylzinc Reagents

An efficient and synthetically convenient method for copper-catalyzed cross-coupling of aryl boronic acids with perfluoroalkyl zinc reagents has been described. The reaction proceeds under mild reaction conditions with a high efficiency and broad substrate scope and provides a general access to perfluoroalkylated arenes, which are of interest in life and materials science.

Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Secondary α-(Trifluoromethyl)benzyl Tosylates.

A palladium-catalyzed C(sp3 )-C(sp2 ) Suzuki-Miyaura cross-coupling of aryl boronic acids and α-(trifluoromethyl)benzyl tosylates is reported. A readily available, air-stable palladium catalyst was employed to access a wide range of functionalized 1,1-diaryl-2,2,2-trifluoroethanes. Enantioenriched α-(trifluoromethyl)benzyl tosylates were found to undergo cross-coupling to give the corresponding enantioenriched cross-coupled products with an overall inversion in configuration. The crucial role of the CF3 group in promoting this transformation is demonstrated by comparison with non-fluorinated derivatives.

Active Palladium Colloids via Palladacycle Degradation as Efficient Catalysts for Oxidative Homocoupling and Cross-Coupling of Aryl Boronic Acids

Active palladium colloids formed upon degradation of a palladacyclic complex (Herrmann–Beller 1) have been isolated for the first time and thoroughly characterized with techniques such as transmission electron microscopy (TEM), high-resolution TEM, X-ray photoelectron spectroscopy (XPS), and extended X-ray absorption fine structure spectroscopy. The synthesized palladium colloids have been utilized as efficient catalysts for the oxidative homocoupling of aryl boronic acids. Cross-coupling of two different aryl boronic acids has also been made possible using these active palladium colloids. This is the first report of this kind of coupling between aryl boronic acids.

A Highly Efficient Copper‐Mediated Radioiodination Approach Using Aryl Boronic Acids

A convenient and quantitative radioiodination method by copper-mediated cross-coupling of aryl boronic acids was developed. The mild labeling conditions, ready availability of the boronic acid substrate, simple operation, broad functional group tolerance and excellent radiochemical yield (RCY) make this a practical strategy for radioiodine labeling without further purification.

ChemInform Abstract: Palladium‐Catalyzed Arylation of Arylboronic Acids with Yagupolskii—Umemoto Reagents.

AbstractThe reaction is applicable to aryl.

Copper-catalyzed C–N cross-coupling of arylboronic acids with N-acylpyrazoles

A copper-catalyzed C–N bond forming reaction of arylboronic acids and N-acylpyrazoles was developed. This procedure used N-acetyl protected pyrazoles as starting material instead of free pyrazoles (NH). The reaction worked under neutral conditions and did not require any base or ligand. The reaction showed good functional group tolerance.

Visible-light-driven Photocatalytic N-arylation of Imidazole Derivatives and Arylboronic Acids on Cu/graphene catalyst.

N-aryl imidazoles play an important role as structural and functional units in many natural products and biologically active compounds. Herein, we report a photocatalytic route for the C-N cross-coupling reactions over a Cu/graphene catalyst, which can effectively catalyze N-arylation of imidazole and phenylboronic acid, and achieve a turnover frequency of 25.4 h−1 at 25 oC and the irradiation of visible light. The enhanced catalytic activity of the Cu/graphene under the light irradiation results from the localized surface plasmon resonance of copper nanoparticles. The Cu/graphene photocatalyst has a general applicability for photocatalytic C-N, C-O and C-S cross-coupling of arylboronic acids with imidazoles, phenols and thiophenols. This study provides a green photocatalytic route for the production of N-aryl imidazoles.

Nickel-Catalyzed C–P Cross-Coupling of Arylboronic Acids with P(O)H Compounds

A novel and efficient Ni-catalyzed coupling of a wide range of arylboronic acids with H-phosphites, H-phosphinate esters, and H-phosphine oxides has been developed, providing a general and powerful tool for the synthesis of various aryl-phosphorus compounds, especially for valuable triarylphosphine oxides, in good to excellent yield. This protocol is the first Ni-catalyzed C-P bond-forming reaction between arylboronic acids and P(O)H compounds.

ChemInform Abstract: Cu2O‐Mediated Room Temperature Cyanation of Aryl Boronic Acids/Esters and TMSCN.

A method for the efficient and reliable synthesis of aryl nitriles via the Cu2O-catalyed cross-coupling of aryl boronic acids or esters and TMSCN is presented. A broad range of substrates decorated by electron-rich and deficient, sterically very congested, and labile functionalities were tolerated. Moreover, the reaction can proceed under mild conditions at room temperature. These advantages paired with the use of cheap, readily available, and halogen-free Cu2O as catalysts make the protocol an appealing option for aryl cyanations.

Thiophene-Core Estrogen Receptor Ligands Having Superagonist Activity

To probe the importance of the heterocyclic core of estrogen receptor (ER) ligands, we prepared a series of thiophene-core ligands by Suzuki cross-coupling of aryl boronic acids with bromo-thiophenes and we assessed their receptor binding and cell biological activities. The disposition of the phenol substituents on the thiophene core, at alternate or adjacent sites, and the nature of substituents on these phenols, all contribute to binding affinity and subtype selectivity. Most of the bis(hydroxyphenyl)-thiophenes were ERβ selective, whereas the tris(hydroxyphenyl)-thiophenes were ERα selective; analogous furan-core compounds generally have lower affinity and less selectivity. Some diarylthiophenes show distinct superagonist activity in reporter gene assays, giving maximal activities 2-3 times that of estradiol, and modeling suggests that these ligands have a different interaction with a hydrogen-bonding residue in helix-11. Ligand-core modification may be a new strategy for developing ER ligands whose selectivity is based on having transcriptional activity greater than that of estradiol.

Synthesis of N-Aryl-4,5,6,7-tetrahydroindoles

Indole, unlike pyrrole, undergoes electrophilic substitution at C-3. For example, a Vilsmeier reaction of indole gives 3formylindole exclusively. On the other hand, the same reaction with pyrrole produces 2-formylpyrrole. If the introduction of a nucleophile at the C-2 of indole is desired, 4,5,6,7-tetrahydroindole should be employed as a starting material. An introduction of the substitution and a subsequent dehydrogenation of the tetrahydroindole should be carried out to complete the synthesis of the 2-substituted indole. For such purpose we previously reported the synthesis of 5-substituted 4,5,6,7-tetrahydroindoles from cyclohexanones with suitable substituents at 4-position of the cyclic ketone. As an extension of such a synthesis, we were interested in the preparation of N-aryl-4,5,6,7-tetrahydroindoles. One way of introducing the aryl group is to apply C-N bond formation reaction, which has been an active research area in the past decade. Numerous reports can be found in literature on the N-arylation of indole. However, there are a few reports on the direct arylation of 4,5,6,7-tetrahydroindoles. Bekolo reported the N-arylation of 4,5,6,7-tetrahydro-4oxoindole (3) to prepare the N-aryl-4,5,6,7-tetrahydro-4oxoindole (5) by the cross coupling of arylboronic acids, pZ-C6H4-B(OH)2 (Z = H, o-Me, p-t-Bu, p-OEt, p-Cl) in the presence of Cu(OAc)2 and ethyl diisopropylamine in dichloromethane solution at room temperature. But the yields were in the range of 43-70% after 6-14 days of reaction time. Nishio, et. al. prepared N-aryl-4,5,6,7-tetrahydroindoles (6f, 6g, 6h, 6i) from 1-aryl-1,4,5,6,7,7a-hexahydro-2H-indol-2ones by using Lawesson’s reagent [2,4-bis-(p-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide] in 2755% yields. Olesen et al. reported the preparation of 6f, 6g, and 6i by the reactions of the corresponding cyclohexanone imines with 2-chloroacrylonitrile in 25-61% yields. Obviously, direct arylation of the tetrahydroindole (4) to synthesize the N-aryltetrahydroindole (6) requires a decent method for the preparation of 4. There are several reports for such preparations using cyclohexanone as starting material. It was converted to a dimethylhydrazone which was reacted with n-BuLi to give 1-dimethylamino-4,5,6,7-tetrahydroindole, but the removal of the dimethylamino group was not efficient. Alternatively, cyclohexanone was converted to an oxime, which was reacted with acetylene in KOH and DMSO. But the method suffers the disadvantage of the formation of N-vinyl derivatives of 4. An oxime prepared from O-(2-hydroxyethyl)hydroxylamine could be converted to 4 upon the exchange of the –OH with iodine and subsequent cyclization by t-BuOK in t-BuOH in good yield. Tetrahydroindole (4) itself is very unstable, requiring storage in a freezer under N2. 3 Furthermore, C-N bond formation is an additional step which requires the use of a transition metal catalyst. Therefore, a shorter procedure in which the N-aryl group was introduced in the earlier step is desirable. Here we report a three-step preparation of N-aryl4,5,6,7-tetrahydroindoles (6) from cyclohexane-1,3-dione (1). There are two reports of employing 1 for similar purpose. Martifnez et al. treated 1 with chloroacetone to prepare 2-(2oxo-1-propyl)-1,3-cyclohexanedione, which was converted to 2-methyl derivatives of 5. Piras et al. reacted 1 with ethyl bromopyruvate in the presence of EtOH/KOH under reflux conditions to prepare 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid, and then converted to 5a and 5g by heating with aniline and p-methoxyaniline, respectively, in 75% yield.

ChemInform Abstract: Pd/C: An Efficient, Heterogeneous and Reusable Catalyst for Phosphane‐Free Carbonylative Suzuki Coupling Reactions of Aryl and Heteroaryl Iodides.

AbstractCarbonylative Suzuki cross coupling of arylboronic acids with (het)aryl iodides is efficiently catalyzed by Pd—C to give (het)aryl aryl ketones in moderate to high yields.

ChemInform Abstract: Coupling of Heteroaryl Chlorides with Arylboronic Acids in the Presence of (1,4-Bis-(diphenylphosphine)butane)palladium(II) Dichloride.

Abstract The cross-coupling of arylboronic acids with a variety of π-deficient heteroaryl chlorides has been shown to occur in high yield in the presence of [1,4-bis-(diphenylphosphine)butane]palladium(II) dichloride as catalyst.

Fluorous Tagged N-Hydroxy Phthalimide for the Parallel Synthesis of O-Aryloxyamines

The parallel synthesis of O-aryloxyamines remains an unfulfilled need in the field of medicinal chemistry and fragment-based approaches. To fill this gap a solution-phase two-step process based on (1) a copper-catalyzed cross-coupling of aryl boronic acids with a fluorous tagged N-hydroxyphthalimide, and (2) a supported aminolysis was designed and optimized using Taguchi's method. A library of O-aryloxyamines was synthesized in high yields with high purity and diversity.

Cross Coupling of Arylboronic Acids with Imidazoles by Sulfonatocopper(II)(salen) Complex in Water

Abstract A mild and clean protocol for the cross coupling reactions between imidazoles and arylboronic acids has been developed in good to excellent yields up to 98% in the presence of sulfonatocopper(II)(salen) catalyst in water without addition of other additives and bases.

Palladium-catalyzed decarboxylative cross-coupling of alkynyl carboxylic acids with arylboronic acids

A highly efficient and mild palladium-catalyzed decarboxylative cross-coupling of aryl boronic acids and alkynyl carboxylic acids for the synthesis of unsymmetrical substituted alkynes is described for the first time.