Highly efficient synthesis of aryl ketones by PEPPSI-palladium catalyzed acylative Suzuki coupling of amides with diarylborinic acids

An improved acylative cross-coupling of various N-methyl-N-tosyl amides with diarylborinic acids for synthesis of aryl ketones is developed. In most cases, aryl ketones could be obtained in excellent yields by using 1?mol% 2,6-diisopropylphenylimidazolylidene and 3-chloropyridine co-supported palladium chloride as catalyst in the presence of 3 equiv. K₂CO₃ as base in refluxing THF. The readily prepared and cost-effective substrates, N-methyl-N-tosylamides and diarylborinic acids, and the commercially available catalyst system promise a practical and efficient access to aryl ketones.     

A highly efficient and recyclable NiCl2(dppp)/PEG-400 system for Suzuki-Miyaura reaction of aryl chlorides with arylboronic acids

Abstract

NiCl₂(dppp) in PEG-400 is shown to be a highly efficient catalyst for Suzuki-Miyaura coupling of aryl chlorides with arylboronic acids. The reaction could be conducted at 100?°C using K₃PO₄ as base, yielding a variety of biaryls in good to excellent yields. The isolation of the products was readily performed by extraction with petroleum ether and NiCl₂(dppp)/PEG-400 system could be easily recycled and reused up to five times without significant loss of activity. Our system not only avoids the use of easily volatile and toxic dioxane or toluene as a solvent but also solves the basic problem of nickel catalyst reuse.     

Carbene adduct of cyclopalladated ferrocenylimine: Efficient catalyst for the Suzuki coupling of sterically hindered aryl chlorides with a weaker base and low catalyst loading

One-pot synthesis of the N,N′-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) adduct of cyclopalladated ferrocenylimine complex 1 has been described. This complex has been successfully applied to Suzuki coupling reaction. Various aryl chlorides and boronic acids can be coupled efficiently with a mild base K₃PO₄·7H₂O and low catalyst loadings. This system has been proven to be compatible with the sterically hindered aryl chlorides and some boronic acids leading to form di- and tri-ortho-substituted biaryls in high yields.     

Indolylbenzimidazole‐based ligands catalyze the coupling of arylboronic acids with aryl halides

A novel class of compounds bearing indole and benzimidazole rings was designed and easily synthesized from 2‐indolecarboxylic acid and o‐phenylenediamine. The catalytic system derived from a 2‐indolylbenzimidazole‐based ligand and Pd(OAc)₂ in situ could lead to complete conversion of aryl bromides at 0.5 mol% Pd loading under mild reaction conditions. In the presence of a catalyst, sterically hindered biaryls were selectively generated in excellent yields by adjusting reaction parameters through the coupling of arylboronic acids with aryl halides. The efficiency of this reaction was demonstrated by its compatibility with various functional groups.     

Synthesis,characterization and catalytic activity of new aminomethyldiphosphine–Pd(II) complexes for Suzuki cross‐coupling reaction

A new range of CF₃‐substituted aminomethyldiphosphine (P―C―N) ligands ((C₆H₅)₂PCH₂)₂NR (R = ―C₆H₄(2‐CF₃) ( 1 ), ―C₆H₄(3‐CF₃) ( 1b ) has been synthesized from 2‐(trifluoromethyl)aniline and 3‐(trifluoromethyl)aniline with diphenylphosphine. The aminomethyldiphosphine ligands were reacted with Pd(cod)Cl₂ to give corresponding metal complexes, PdLCl₂ ( 2a , 2b ). The aminomethyldiphosphine–palladium compounds were characterized by utilizing several methods including NMR (¹H, ¹³C, ³¹P) and elemental analysis. These compounds were used as catalysts in Suzuki cross‐coupling reaction of aryl chlorides and bromides. The effect of base was also investigated in this current project. CF₃‐substituted aminomethyldiphosphine–palladium complexes were found to be efficient catalysts in Suzuki cross‐coupling reaction of activated and deactivated aryl boronic acids. Copyright © 2013 John Wiley & Sons, Ltd.     

A nickel precatalyst for efficient cross-coupling reactions of aryl tosylates with arylboronic acids: vital role of dppf

An air-stable and easy-to-handle nickel precatalyst, (9-phenanthrenyl)Ni(II)(PPh₃)₂Cl, was examined for the cross-coupling reactions of aryl tosylates with arylboronic acids. Under the optimized reaction conditions, the catalytic system tolerates a wide range of activated, neutral and deactivated substrates. The selectivity of this cross-coupling reaction towards aryl tosylates and arylboronic acids has been investigated. It is proposed that ligand 1,1′-bis(diphenylphosphino)ferrocene (dppf) plays a key role in the coupling by enforcing a cis geometry in key intermediates and the active Ni(0) species.     

Catalytic Decarboxylative Cross‐Coupling of Aryl Chlorides and Benzoates without Activating ortho Substituents

The restriction of decarboxylative cross‐coupling reactions to ortho‐substituted or heterocyclic carboxylate substrates was overcome by holistic optimization of a bimetallic Cu/Pd catalyst system. The combination of a CuI/Me₄phen decarboxylation catalyst and a [(MeCN)₄Pd](OTf)₂/XPhos cross‐coupling catalyst enables the synthesis of biaryls from inexpensive aryl chlorides and potassium benzoates regardless of their substitution pattern.     

Synthesis of substituted biaryls via Suzuki,Stille and Hiyama cross‐coupling and homo‐coupling reactions by CN‐dimeric and monomeric ortho‐palladated catalysts

The catalytic activity of dimeric [Pd{C₆H₂(CH₂CH₂NH₂)–(OMe)₂,2,3}(μ‐Br)]₂ and monomeric [Pd{C₆H₂(CH₂CH₂NH₂)–(OMe)₂,2,3}Br(PPh₃)] complexes as efficient, stable and air‐ and moisture‐tolerant catalysts was investigated in the Suzuki, Stille and Hiyama cross‐coupling and homo‐coupling reactions of various aryl halides. Substituted biaryls were produced in excellent yields in short reaction times using catalytic amounts of these complexes. The monomeric complex was demonstrated to be more active than the corresponding dimeric catalyst for the cross‐coupling reaction of unreactive aryl bromides and chlorides. The combination of homogeneous metal catalysts and microwave irradiation gave higher yields of products in shorter reaction times. Copyright © 2013 John Wiley & Sons, Ltd.     

Generation of Organozinc Reagents by Nickel Diazadiene Complex Catalyzed Zinc Insertion into Aryl Sulfonates

The generation of arylzinc reagents (ArZnX) by direct insertion of zinc into the C−X bond of ArX electrophiles has typically been restricted to iodides and bromides. The insertions of zinc dust into the C−O bonds of various aryl sulfonates (tosylates, mesylates, triflates, sulfamates), or into the C−X bonds of other moderate electrophiles (X=Cl, SMe) are catalyzed by a simple NiCl₂–1,4-diazadiene catalyst system, in which 1,4-diazadiene (DAD) stands for diacetyl diimines, phenanthroline, bipyridine and related ligands. Catalytic zincation in DMF or NMP solution at room temperature now provides arylzinc sulfonates, which undergo typical catalytic cross-coupling or electrophilic substitution reactions.     

Palladium‐Catalyzed Suzuki‐Miyaura Type Coupling Reaction of Aryl Halides with Triphenylborane‐Pyridine

The Suzuki‐Miyaura type coupling reaction of aryl halides with triphenylborane‐pyridine was described. The reaction can be catalyzed by Pd(OAc)₂ (5 mol%) in presence of Cs₂CO₃ at 50°C or 80°C, and functionalized biaryls were obtained in good to excellent yields. This protocol is general and can tolerate a wide range of functional groups.     

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.     

Application of ortho‐palladated homoveratrylamine complex containing mixed phosphorus–nitrogen donors in the Suzuki reaction

The catalytic activity of [Pd{C₆H₂(CH₂CH₂NH₂)‐(OMe)₂,3,4}Br(PPh₃)] monomeric ortho‐palladated complex of homoveratrylamine and triphenylphosphine was investigated in the Suzuki cross‐coupling reaction of various aryl halides with aryl boronic acids. The substituted biaryls were produced in excellent yields using a catalytic amount of this complex in ethanol at 60°C. Copyright © 2012 John Wiley & Sons, Ltd.     

Efficient cyanation of aryl halide with K4[Fe(CN)6]⋅3H2O catalyzed by a P–O bidentate chelate palladium complex under air

Cyanation of aryl halide with K₄[Fe(CN)₆]?3H₂O has been carried out in the presence of a high‐activity catalyst: an air‐stable P–O bidentate chelate palladium complex. This method is applicable to both activated and deactivated aryl halides, and even a variety of aromatic nitriles are obtained in good yields under aerobic conditions. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

Poly(iminomethylene) copolymers

Copolymerization of an isocyanide giving an insoluble homopolymer with another isocyanide giving a soluble homopolymer in ethanol solution using 0.5–1% of a nickel (II) catalyst in many cases gives a soluble copolymer containing pendant groups arising from both isocyanides. Thus, methyl isocyanide, which gives an insoluble homopolymer, gives chloroform-soluble copolymers incorporating 39–44% of pendant methyl groups when copolymerized with equimolar amounts of tert-butyl isocyanide or several aryl isocyanides. Similarly, cyclohexyl isocyanide, which also gives an insoluble homopolymer, gives chloroform-soluble copolymers incorporating 43–59% of pendant cyclohexyl groups when copolymerized with equimolar amounts of several aryl isocyanides. The compositions, chloroform solubilities, and polystyrene equivalent molecular weights are given for 33 different copolymers obtained by copolymerizations of various equimolar binary mixtures of the monomers CH₃NC, (CH₃)₃CNC, cyclo-C₆H₁₁NC, C₂H₅NC, CH₃CH?CHNC,(CH₃)₂C?CHNC, 2,4,6-(CH₃)₃C₆H₂CH?CHNC, C₆H₅CH(CH₃)NC, CH₂?CHNC, (CH₃)₃CCH?CHNC, C₆H₅NC, 2- and 4-CH₃C₆H₄NC and 2-, 3-, 4-CH₃OC₆H₄NC using the nickel (II) catalyst system.     

Facile synthesis of alkynyl‐, aryl‐ and ferrocenyl‐substituted pyrazoles via Sonogashira and Suzuki–Miyaura approaches

A concise and efficient synthesis of densely substituted novel pyrazoles with alkynyl, aryl and ferrocenyl functionalities is reported, providing a platform for biological studies. The general strategy involves Sonogashira and Suzuki–Miyaura cross‐coupling reactions of easily obtainable 5‐ferrocenyl/phenyl‐4‐iodo‐1‐phenylpyrazoles with terminal alkynes and boronic acids, respectively. The starting 4‐iodopyrazoles were synthesized by electrophilic cyclization of α,β‐alkynic hydrazones with molecular iodine. Sonogashira reactions have been achieved by employing 5 mol% PdCl₂(PPh₃)₂, 5 mol% CuI, excess Et₃N and 1.2 equiv. of terminal alkyne, relative to 4‐iodopyrazole, in tetrahydrofuran at 65 °C, while Suzuki–Miyaura reactions have been accomplished using 5 mol% PdCl₂(PPh₃)₂ and 1.4 equiv. of both boronic acid/ester and KHCO₃, with respect to 4‐iodopyrazole, in 4:1 dimethylformamide–H₂O solution at 110 °C. Both Sonogashira and Suzuki–Miyaura coupling reactions have proven effective for the synthesis of alkynyl‐, aryl‐ and ferrocenyl‐substituted pyrazoles and demonstrated good tolerance to a diverse range of substituents, including electron‐donating and electron‐withdrawing groups. These coupling approaches could allow for the rapid construction of a library of functionalized pyrazoles of pharmacological interest. Copyright © 2016 John Wiley & Sons, Ltd.     

Syntheses,spectroscopy, and X-ray structures of 3-{(R)-(Ar)-ethylimino}-1,3-dihydro-indol-2-one (Ar = Ph,MeOC6H4, BrC6H4, 1-naphthyl) and [Rh(η4-cod){3-((R)-(Ar)-ethylimino)-3H-indol-2-olato}]

Condensation of 1H-indole-2,3-dione (isatin) with (R)-(Ar)-ethylamines gives enantiopure Schiff bases, 3-{(R)-(Ar)-ethylimino}-1,3-dihydro-indol-2-one (HL) {Ar?=?Ph (HL1), 2-MeOC₆H₄ (HL2), 4-MeOC₆H₄ (HL3), 4-BrC₆H₄ (HL4), and 1-naphthyl (HL5)}. The Schiff bases readily coordinate to [Rh(μ-O₂CMe)(η⁴-cod)]₂ (cod?=?1,5-cyclooctadiene) to give mononuclear [Rh(η⁴-cod){3-((R)-(Ar)-ethylimino)-3H-indol-2-olato}] {Ar?=?Ph (1), 4-MeOC₆H₄ (2), and 4-BrC₆H₄ (3)}, respectively. The Schiff bases and complexes have been fully characterized by IR, UV-Vis, ¹H-NMR, mass, and circular dichroism (CD) spectrometry. Polarimetry and CD measurements show the enantiopurity of the Schiff bases as well as the complexes. ¹H NMR measurements reveal slow conversion of the lactam to the enol form of the Schiff bases in solution. In the solid state the lactam form dominates as shown by crystal structures of HL1 and HL4. While gross structural features of both are similar, the molecules differ significantly in the relative orientations of the aryl and lactam rings. The difference is mostly rotation about the N2–C9 bond with different C8–N2–C9–C11 torsion angle of +89.77(12)° for HL1 and C2–N2–C9–C11 of +106.8(3)° for HL4.     

Acceleration of CuI-catalyzed coupling reaction of alkyl halides with aryl Grignard reagents using lithium chloride

In the presence of LiCl, CuI-catalyzed coupling reaction of R(alkyl)-X with Ar(aryl)MgBr at rt was completed within 2 h. Effective leaving groups X in R-X were Br, I, OTs, but not Cl. Grignard reagents ArMgBr with both standard and bulky Ar such as 2-MeC₆H₄, 2-MeOC₆H₄, and 2,6-(Me)₂C₆H₃ afforded the desired products in good yields. Ester and cyano groups in R-X were tolerated. Coupling reaction with R(alkyl)-MgBr proceeded as well.     

Ligation state of nickel during CO bond activation with monodentate phosphines

The oxidative addition of phenolic electrophiles at Ni(0) in the presence of monodentate phosphine ligands was studied with both dispersion-free and dispersion-containing DFT methods. With the popular bulky ligand PCy₃, consideration of dispersion has a striking effect on the predicted ligation state of nickel during oxidative addition of aryl sulfamates. Dispersion-containing methods such as M06L indicate a clear preference for a bis-phosphine ligated transition state (TS), while dispersion free methods like B3LYP strongly favor a mono-phosphine ligated TS. This discrepancy in predicted ligation state is also found with small phosphines (PMe₃) in combination with some aryl electrophiles (carbamates, acetates, pivalates, chlorides), but a bis-PMe₃-ligated TS is predicted regardless of dispersion for other electrophiles (sulfamates, mesylates, tosylates). DFT calculations that include dispersion also offer a possible explanation for the observed poor efficacy of P^tBu₃ as a ligand in Ni-catalyzed cross-coupling reactions.     

Direct arylation of oxazole and benzoxazole with aryl or heteroaryl halides using a palladium-diphosphine catalyst

Through the use of PdCl(dppb)(C₃H₅) as a catalyst, a range of aryl bromides and chlorides undergoes coupling via C-H bond activation/functionalization reaction with oxazole or benzoxazole in good yields. This air-stable catalyst can be used at low loadings with several substrates. Surprisingly, better results in terms of substrate/catalyst ratio were obtained in several cases using electron-excessive aryl bromides than with the electron-deficient ones. This seems to be mainly due to the relatively low thermal stability of some of the 2-arylbenzoxazoles formed with electron-deficient aryl halides. With these substrates, in order to obtain higher yields of product, the reactions had to be performed at a lower temperature (100-120 °C) using a larger amount of catalyst. On the other hand, in the presence of the most stable products, the reactions were performed at 150 °C using as little as 0.2 mol% catalyst. Arylation of benzoxazole with heteroaryl bromides also gave the coupling products in moderate to high yields using 0.2-5 mol% catalyst. With this catalyst, electron-deficient aryl chloride such as 4-chlorobenzonitrile, 4-chloroacetophenone or 2-chloronitrobenzene have also been used successfully.