Suzuki Coupling of Cyclopropylboronic Acid With Aryl Halides Catalyzed by a Palladium–Tetraphosphine Complex

The tetraphosphine all‐cis‐1,2,3,4‐tetrakis(diphenylphosphinomethyl)cyclopentane (Tedicyp) in combination with [Pd(C₃H₅)Cl]₂ affords a very efficient catalyst for the coupling of cyclopropylboronic acid with aryl bromides and aryl chlorides. Higher reactions rates were observed with aryl bromides than with aryl chlorides; however, even in the presence of 1–0.4% of catalyst, a few aryl chlorides gave the coupling products in good yields. A wide variety of substituents such as alkyl, methoxy, trifluoromethyl, acetyl, benzoyl, formyl, carboxylate, nitro, and nitrile on the aryl halides are tolerated. The coupling reaction of sterically very congested aryl bromides such as bromomesitylene or 2,4,6‐triisopropylbromobenzene also proceeds in good yields.     

Synthesis and formulation of self-immolative PEG-aryl azide block copolymers and click-to-release reactivity with trans-cyclooctene

Self-immolative aryl azides can react with trans-cyclooctenes (TCO), triphenylphosphines or hydrogen sulfide (H₂S) to activate prodrugs, imaging probes and drug delivery systems. To date, the synthesis of polymers containing these aryl azide self-immolative linkers and their reactivity with a strained alkene (i.e., in a bioorthogonal reaction) has not been explored. Also, due to the instability of aryl azides towards light and high temperatures, the polymerization methods compatible with aryl azides are limited. Through systematic investigation of the reversible addition-fragmentation chain transfer (RAFT) and atom transfer radical polymerization (ATRP) methods, a self-immolative PEG-aryl azide block copolymer (PEG₄₅-b-ABOC₂₈ 2 ) and a non-responsive 4-fluoroaryl block copolymer (PEG₄₅-b-FBOC₂₄ 3 ) was prepared. ATRP provided the desired polymers in a highly controlled manner, whereas the RAFT conditions led to higher levels of aryl azide polymer degradation. The ATRP derived polymers 2 and 3 were formulated into nanoparticles of approximately 200 nm diameter, and particle triggering was demonstrated by the [3+2]-cycloaddition reaction of TCO with PEG₄₅-b-ABOC₂₈ 2 in solution (pure polymer) and as a formulated nanoparticle. Preliminary in vitro cell viability studies suggested that the stimuli-responsive aryl azide polymers/nanoparticles are not cytotoxic up to 200 μg/ml concentrations.     

Synthesis and characterization of orthopalladated complexes of 4-chloro benzoylmethylene triphenylphosphorane and their application in Suzuki cross-coupling

Orthopalladated binuclear complexes (1) have been prepared by refluxing a mixture of the phosphorus ylide (ClBPPY) with Pd(OAc)₂ in CH₂Cl₂. Complex 1 reacts with ligands (L) to give (L = PPh₃ (2), Me₃Py (3)). Cyclopalladated complexes are highly efficient catalysts for the Suzuki reactions of aryl bromide with aryl boronic acid. The monomeric complexes 2 and 3 are more active than the dimer 1. Palladium mirror was observed, indicating the involvement of classic Pd(0)/Pd(II) catalytic cycle using these cyclopalladated complexes. The coupling of aryl bromide with aryl boronic acid gave the desired biphenyl congeners in good to excellent yields. We tested the various bases, finding that inorganic bases work better than organic ones.     

Synthese und reaktionen von 1-germcyclohexa-2,4-dienen und 1-germacyclohexa-2,4-dien-eisentricarbonylen

1,1-Diakyl(aryl)4-alkyl(aryl)-4-methoxy-1-germacyclohexa-2,5-dienes undergo ether cleavage with sodium in n-pentane or liquid ammonia. Hydrolysis of the resulting sodium salts yields the 1,1-dialkyl(aryl)-4-alkyl(aryl)-1-germacyclohexa-2,4-dienes. Reduction of 1-chloro-4-methoxy-1-germacyclohexa-2,5-dienes with LiAlH₄ can be directed to give the 1H-1-germacyclohexa-2,4-dienes with ether cleavage.The 1H-1-germacyclohexadienes are chlorinated by PCl₅ and brominated by N-bromosuccinimide to the 1-chloro- or 1-bromo-1-germacyclohexa-2,4-dienes, respectively. 1,1-Diethyl-4-phenyl-4-methoxy-1-germacyclohexa-2,5-diene reacts with PCl₃ with ether cleavage and formation of the 6-chloro-1-germacyclohexa-2,4-diene. Ether cleavage is also possible with BCl₃, the 1-phenyl-1-chloro-4R-4-methoxy-1-germacyclohexa-2,5-dienes are transformed into the 1-phenyl-1,6-dichloro-4R-1-germacyclohexa-2,4-dienes.The Fe(CO)₃ complexes of 1,1-dialkyl(aryl)-1-germacyclohexa-2,4-dienes were synthesized.     

Synthesis and applications of a new palladacycle as a high active catalyst in the Suzuki couplings

The reaction of biphenyl-based phosphine P(o-C₆H₄Me)Ph₂ (1) with Pd(OAc)₂ in toluene affords the air and water stable palladacycle (2) as a binuclear compound which has been characterized by multi-nuclear NMR spectroscopy and elemental analysis as a mixture of cis and trans isomers with relative intensity of 1:3, respectively. This palladacycle is a highly efficient catalyst precursor for the coupling of aryl boronic acids and aryl halides. Both activated and deactivated aryl bromides and chlorides are efficiently coupled in the presence of 2 to furnish the corresponding cross-coupled products in excellent yields, and a wide variety of functional groups are tolerated in aryl halides. This methodology has also been extended for the coupling of bromoarylphosphines and bromoarylphosphine oxides with aryl boronic acids for the generation of hindered corresponding products.     

Synthesis and properties of z-1,3-bis-(aryl)-4-bromo-2-buten-1-ones

Bromination of 1,3-bis(aryl)-2-buten-1-ones by N-bromosuccinimide in anhydrous carbon tetrachloride gives Z-1,3-bis(aryl)-4-bromo-2-buten-1-ones. The effect of the nature of substituent in the benzene ring on the course of a reaction with nucleophiles has been studied. Heating an alcohol solution of these ketones (Ar = 4-MeOC₆H₄, 4-ClC₆H₄) in the presence of acid or in the presence of base (Ar = Ph) gave 2,4-bis(aryl)furans. Treatment of 1,3-bis(aryl)-4-bromo-2-buten-1-ones with thioacetamide gave 2,4-bis(aryl)thiophenes. The oxidation of the halo-substituted dypnones with H₂O₂/NaOH gave (3-bromomethyl-3-aryl-2-oxiranyl)(aryl)methanones. The reaction of halo-substituted dypnones with aryl hydrazines gave 1,3,5-triaryl-1,6-dihydropyridazines or 1,3,5-triarylpyridazinium bromides depending on the structure of the reagents.     

Polyfluoroorganoboron‐Oxygen Compounds. 1 Polyfluorinated Aryl(dihydroxy)boranes and Tri(aryl)boroxins

A general preparative procedure for polyfluorinated aryl(dihydroxy)boranes C₆H_5‐nF_nB(OH)₂ (n = 3 — 5) is described. Polyfluorinated aryl(dihydroxy)boranes are easily dehydrated to the corresponding tri(aryl)boroxins (C₆H_5‐nF_nBO)₃ by thermal or chemical treatment. The property of the acids C₆H_5‐nF_nB(OH)₂ to condensate depends on the number and on the position of the fluorine atoms in the aryl group. Examples of both classes of boron compounds were isolated as pure individuals and characterized by multinuclear NMR spectroscopy.     

Sonogashira reaction of aryl halides with propiolaldehyde diethyl acetal catalyzed by a tetraphosphine/palladium complex

All-cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyzes the Sonogashira reaction of propiolaldehyde diethyl acetal with a variety of aryl bromides and chlorides. A minor electronic effect of the substituents of the aryl bromide was observed. Similar reaction rates were observed in the presence of activated aryl bromides such as 4-trifluoromethylbromobenzene and deactivated aryl bromides such as bromoanisole. Turnover numbers up to 95,000 can be obtained for this reaction. Even aryl chlorides and heteroarylbromides or chlorides have been successfully alkynylated with this catalyst. Moreover, a wide variety of substituents on the aryl halide such as fluoro, trifluoromethyl, acetyl, benzoyl, formyl, nitro, dimethylamino or nitrile are tolerated.     

An Efficient and General Method for Formylation of Aryl Bromides with CO2 and Poly(methylhydrosiloxane)

The formylation of aryl halides with CO₂ to generate aryl aldehydes is challenging. Herein, we report a novel synthesis of aryl aldehydes by formylation of aryl bromides with CO₂ and a waste silane, poly(methylhydrosiloxane) (PMHS). It has been discovered that a simple combination of 1,3‐bis(diphenyphosphino)propane (DPPP)‐chelated Pd catalyst, Pd(DPPP)Cl₂, with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) is able to effectively catalyze the reaction, leading to aryl aldehydes in moderate to excellent yields, and without any by‐products in most cases. Moreover, this route could be extended to the formylation of aryl iodides with high efficiency. This approach is simple, less costly, and environmentally friendly, and also widens the applications of CO₂ to form value‐added chemicals by the construction of new C?C bonds.     

Efficient cyanation of aryl bromides with K4[Fe(CN)6] catalyzed by a palladium-indolylphosphine complex

This study describes a general palladium-catalyzed cyanation of aryl bromides using K₄[Fe(CN)₆] as the cyanide surrogate. The reactions can be successfully conducted under mild reaction conditions (at 50 °C) in mixed solvents (water/MeCN = 1:1) without any surfactant additives, and afford the desired aryl nitriles in good-to-excellent yields. Particularly noteworthy is that this system allows the mildest reaction temperature reported so far for palladium-catalyzed cyanation of aryl bromides with K₄[Fe(CN)₆] source in general. Common functional groups, including keto, aldehyde, free amine, and heterocyclic substrates are compatible under this system. Interestingly, the phosphine ligands bearing -PCy₂ moiety, which usually show excellent activity in aryl halide couplings, are found less effective than the corresponding ligands with -PPh₂ group.     

Scope and Limitations of the s-Block Metal-Mediated Pudovik Reaction

The hydrophosphorylation of phenylacetylene with di(aryl)phosphane oxides Ar₂P(O)H (Pudovik reaction) yields E/Z-isomer mixtures of phenylethenyl-di(aryl)phosphane oxides ( 1 ). Alkali and alkaline-earth metal di(aryl)phosphinites have been studied as catalysts for this reaction with increasing activity for the heavier s-block metals. The Pudovik reaction can only be mediated for di(aryl)phosphane oxides whereas P-bound alkyl and alcoholate substituents impede the P−H addition across alkynes. The demanding mesityl group favors the single-hydrophosphorylated products 1-Ar whereas smaller aryl substituents lead to the double-hydrophosphorylated products 2-Ar . Polar solvents are beneficial for an effective addition. Increasing concentration of the reactants and the catalyst accelerates the Pudovik reaction. Whereas Mes₂P(O)H does not form the bis-phosphorylated product 2-Mes , activation of an ortho-methyl group and cyclization occurs yielding 2-benzyl-1-mesityl-5,7-dimethyl-2,3-dihydrophosphindole 1-oxide ( 3 ).     

Geminally Diaurated Aryls Bridged by Semirigid Phosphine Pillars: Syntheses and Electronic Structure

Geminally diaurated μ₂‐aryl complexes have been prepared where gold(I) centers were bridged by the semirigid diphosphine ligands bis(2‐diphenylphosphinophenyl)ether (DPEphos) and 4,6‐bis(diphenylphosphanyl)dibenzo[b,d]furan (DBFphos). Diaurated complexes were synthesized in ligand redistribution reactions of the corresponding di‐gold dichlorides with di‐gold diaryls (six of them new) and silver(I) salts. Diaurated complexes were isolated as salts of the minimally coordinating anions SbF₆^? and ReO₄^?. Efforts to prepare salts of the tetraarylborate [B(3,5‐(CF₃)₂C₆H₃)₄]^? led to transmetalation from boron, with crystallization of the fluorinated aryl complex. The new complexes were characterized by multinuclear NMR, absorption and emission spectroscopies, 77 K emission lifetimes, and by combustion analysis; three are crystallographically characterized. Structures of geminally diaurated aryl ligands are compared to those of mono‐aurated analogues. Both crystal structures and density‐functional theory calculations indicate slight but observable disruptions of aryl ligand aromaticity by geminal di‐gold binding. An intermolecular aurophilic interaction in one structurally authenticated complex was examined computationally.     

Synthesis of Alkyl-Aryl Ethers by Copper-catalyzed Etherization Reactions of Aryl Fluorides with Tetraalkylammonium Bromides and H2O

Synthesis of alkyl aryl ethers via copper‐catalyzed etherizations of electron‐deficient aryl fluorides with quaternary ammonium bromides and water has been developed. In the presence of Cu(OAc)₂, POPh₃ ( L4 ) and Cs₂CO₃, a variety of electron‐deficient aryl fluorides underwent the reaction with quaternary ammonium bromides and H₂O in moderate to good yields. The mechanism was also discussed.     

Preparation of Complexes of Nickel(II) Aryl Carboxylates with Morpholine and Piperidine

Complexes of nickel(II) aryl carboxylates with a general formula Ni(RC₆H₄COO)₂L₂ where R=H, p-CH₃. p-Cl, m- & p-NO₂; and L = morpholine and piperidine; have been prepared by the interaction of nickel(II) aryl carboxylates with a large excess of appropriate amine. Unlike parent anhydrous nickel(II) aryl carboxylates all these complexes are soluble in common organic solvents.     

Determination of interactions between aryl polyesters and poly(ether imide) via glass transition temperatures of separated phases in immiscible blends

Phase behavior in domains of immiscible blends of poly(pentamethylene terephthalate)/poly(ether imide) (PPT/PEI) and poly(hexamethylene terephthalate)/poly(ether imide) (PHT/PEI) were investigated using differential scanning calorimetry (DSC). The measured glass transition temperature (T _g) reveals that aryl polyesters dissolve more in the PEI-rich phase than the PEI does in the aryl polyester-rich phase, for both PPT/PEI and PHT/PEI systems. Additionally, optical microscopy supports the conclusion that PPT (or PHT) dissolves more in the PEI-rich phase than PEI does in the PPT-rich (or PHT-rich) phase in the aryl polyester/PEI blends. Furthermore, the Flory–Huggins interaction parameters (χ₁₂) for the PPT/PEI and the PHT/PEI blends were calculated to be 0.12 and 0.17, respectively. For the blend systems comprising of PEI and homologous aryl polyesters, the value of χ₁₂ exhibits a trend of variation with respect to structure of aryl polyesters. For the PPT/PEI and PHT/PEI blends, investigated in this study, value of the polymer–polymer interaction parameter (χ₁₂) between the aryl polyester and the PEI was found to be positive, which increases with the number of methylene moieties in the repeating unit of the aryl polyester, ultimately resulting in phase separation observed.     

Diphenylphosphorylated PEG (DPPPEG) as a new support for generation of nano-Pd(0) as catalyst for carbon–carbon bond formation via copper-free Sonogashira and homocoupling reactions of aryl halides in PEG

In this study, synthesis and application of diphenylphosphorylated PEG₂₀₀ (DPPPEG₂₀₀) are described. Herein, we report a very simple procedure for the preparation of DPPPEG₂₀₀ as a stable solid through the reaction of PEG₂₀₀ with ClPPh₂. This compound was used as a very suitable ligand for the in situ generation of nano-Pd(0) particles through its reaction with PdCl₂ as a pre-catalyst. Isolation of this catalyst is very simple through addition of diethyl ether to the reaction mixture and centrifugations. Full characterization of the nano-Pd(0)/DPPPEG200 was performed by XRD spectra, UV–Vis spectra, and also by TEM image. This nano-complex was used as an efficient catalyst for copper-free Sonogashira and homocoupling reactions of aryl halides. The sonogashira reaction of aryl halides was conducted at 80 °C in PEG. However, the homocoupling reaction was performed at 100 °C for aryl iodides and activated aryl bromides and at 130 °C for deactivated aryl bromides and aryl chlorides in PEG. The catalyst was recovered and recycled for four consecutive runs.     

Efficient nickel/N-heterocyclic carbene catalyzed C-S cross-coupling

The cross-coupling reaction of aryl halides with aliphatic and aromatic thiols catalyzed by readily available Ni(OAc)₂ with N-heterocyclic carbene (NHC) is reported. Ni(OAc)₂/NHC catalyst showed good activities toward various aryl halides in C-S coupling reaction, even with aryl chlorides. Reactions occurred in excellent yields, broad scope, and high tolerance of functional groups.     

In Situ Generation of ArCu from CuF2 Makes Coupling of Bulky Aryl Silanes Feasible and Highly Efficient

A bimetallic system of Pd/CuF₂, catalytic in Pd and stoichiometric in Cu, is very efficient and selective for the coupling of fairly hindered aryl silanes with aryl, anisyl, phenylaldehyde, p‐cyanophenyl, p‐nitrophenyl, or pyridyl iodides of conventional size. The reaction involves the activation of the silane by Cu^II, followed by disproportionation and transmetalation from the Cu^I(aryl) to Pd^II, upon which coupling takes place. Cu^III formed during disproportionation is reduced to Cu^I(aryl) by excess aryl silane, so that the CuF₂ system is fully converted into Cu^I(aryl) and used in the coupling. Moreover, no extra source of fluoride is needed. Interesting size selectivity towards coupling is found in competitive reactions of hindered aryl silanes. Easily accessible [PdCl₂(IDM)(AsPh₃)] (IDM = 1,3‐dimethylimidazol‐2‐ylidene) is by far the best catalyst, and the isolated products are essentially free from As or Pd (<1 ppm). The mechanistic aspects of the process have been experimentally examined and discussed.     

threo‐2‐(2,6‐Dimethoxy­phen­oxy)‐1‐(4‐hydr­oxy‐3,5‐dimethoxy­phenyl)­propane‐1,3‐diol: a conformational study

In the crystal structure of the title compound, C₁₉H₂₄O₈, the mol­ecules adopt a conformation in which the bulky 2,6‐dimethoxy­phen­oxy and 4‐hydr­oxy‐3,5‐dimethoxy­phen­yl groups are almost as far apart as possible. The C(aryl)·C(aryl) distance is 4.8766 (19) Å, which is close to the calculated maximum value (4.92 Å). The C(aryl)—C—C—O(aryloxy) torsion angle is 173.76 (11)° and the C(benzylic)—C—O—C(aryl) torsion angle is 149.09 (11)°. The conformation is compared with those of related lignin model compounds. The hydrogen‐bonding pattern is discussed in terms of graph‐set theory.     

[PdCl2{8-(di-tert-butylphosphinooxy)quinoline)}]: a highly efficient catalyst for Suzuki-Miyaura reaction

The complex [PdCl₂(P-N)] containing the basic and sterically demanding 8-(di-tert-butylphosphinooxy)quinoline ligand (P-N) is a highly efficient catalyst for the coupling of phenylboronic acid with aryl bromides or aryl chlorides. The influence of solvent and base has been investigated, the highest rates being observed at 110 °C in toluene with K₂CO₃ as the base. With aryl bromides the reaction rates are almost independent on the electronic properties of the para aryl substituents, on the contrary, reduced reaction rates are observed when bulky substituents are present on the substrate. Nevertheless the coupling of 2-bromo-1,3,5-trimethylbenzene with phenylboronic acid can be carried out to completion in 2 h using a catalyst loading of 0.02 mol %. Under optimized reaction conditions, turnover frequencies as high as 1900 h⁻¹ can be obtained in the coupling of 4-chloroacetophenone with phenylboronic acid; lower reaction rates are obtained with substrates bearing EDG substituents on the aryl group.