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.     

Palladium‐catalysed reductive carbonylation of aryl halides with iron pentacarbonyl for synthesis of aromatic aldehydes and deuterated aldehydes

The first use of iron pentacarbonyl is described for the novel and efficient conversion of aryl iodides, bromides and chlorides into their corresponding aryl aldehydes and/or aryl deuterated aldehydes. The reaction is catalysed with Pd(0) in aqueous N,N‐dimethylformamide at atmospheric pressure. In this protocol, neither gaseous hydrogen nor any reducing agent is required for the formation of the carbonylated product. The reaction can be performed without a P(III) ligand for aryl iodides; however, employing a P(III) ligand is necessary to perform the reaction with aryl bromides and chlorides. Copyright © 2015 John Wiley & Sons, Ltd.     

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.     

Pd/P(t-Bu)(3): a mild and general catalyst for Stille reactions of aryl chlorides and aryl bromides

Pd/P(t-Bu)(3) serves as an unusually reactive catalyst for Stille reactions of aryl chlorides and bromides, providing solutions to a number of long-standing challenges. An unprecedented array of aryl chlorides can be cross-coupled with a range of organotin reagents, including SnBu(4). Very hindered biaryls (e.g., tetra-ortho-substituted) can be synthesized, and aryl chlorides can be coupled in the presence of aryl triflates. The method is user-friendly, since a commercially available complex, Pd(P(t-Bu)(3))(2), is effective. Pd/P(t-Bu)(3) also functions as an active catalyst for Stille reactions of aryl bromides, furnishing the first general method for room-temperature cross-couplings.     

NiCl(2)(dppe)-catalyzed cross-coupling of aryl mesylates, arenesulfonates, and halides with arylboronic acids

An investigation of the NiCl(2)(dppe)-, NiCl(2)(dppb)-, NiCl(2)(dppf)-, NiCl(2)(PCy(3))(2)-, and NiCl(2)(PPh(3))(2)-catalyzed cross-coupling of the previously unreported aryl mesylates, and of aryl arenesulfonates, chlorides, bromides, and iodides containing electron-withdrawing and electron-donating substituents with aryl boronic acids, in the absence of a reducing agent, is reported. NiCl(2)(dppe) was the only catalyst that exhibited high and solvent-independent activity in the two solvents investigated, toluene and dioxane. NiCl(2)(dppe) with an excess of dppe, NiCl(2)(dppe)/dppe, was reactive in the cross-coupling of electron-poor aryl mesylates, tosylates, chlorides, bromides, and iodides. This catalyst was also efficient in the cross-coupling of aryl bromides and iodides containing electron-donating substituents. Most surprisingly, the replacement of the excess dppe from NiCl(2)(dppe)/dppe with excess PPh(3) generated NiCl(2)(dppe)/PPh(3), which was found to be reactive for the cross-coupling of both electron-rich and electron-poor aryl mesylates and chlorides. Therefore, the solvent-independent reactivity of NiCl(2)(dppe) provides an inexpensive and general nickel catalyst for the cross-coupling of aryl mesylates, tosylates, chlorides, bromides, and iodides with aryl boronic acids.     

Synthesis of primary aromatic amides by aminocarbonylation of aryl halides using formamide as an ammonia synthon

Primary aromatic amides were prepared by a palladium-catalyzed aminocarbonylation reaction of aryl halides in high yields (70-90%) using formamide as the amine source. The reactions require a palladium catalyst in combination with a nucleophilic Lewis base such as imidazole or 4-(dimethylamino)pyridine (DMAP). Aryl, heteroaryl, and vinyl bromides and chlorides were converted to the primary amides under mild conditions (5 bar, 120 degrees C) using 1 mol % of a palladium-phosphine complex. Best results were obtained in dioxane using triphenylphosphine as the ligand and DMAP as the base. For activated aryl bromides, a phosphine-to-palladium ratio of 2:1 was sufficient, but less reactive aryl bromides or aryl chlorides required ligand-to-palladium ratios up to 8:1 in order to stabilize the catalyst and achieve full conversion. The influence of catalyst, base, solvent, pressure, and temperature was studied in detail. The mechanism of the reaction could be clarified by isolating and identifying the reaction intermediates. In addition, methylamides and dimethylamides were prepared by the same method using N-methylformamide and N,N-dimethylformamide as the amine source.     

Highly efficient orthopalladated complexes of second and third benzyl amine for catalyzing the Suzuki cross‐coupling reaction

In this work, ortho‐palladated complexes [Pd(µ‐Cl)(C₆H₄CH₂ NRR′‐κ²‐C,N)]₂ and [Pd(C₆H₄CH₂NH₂‐2‐C,N)Cl(Y)] were tested in the Suzuki–Miyaura cross‐coupling reaction. Cyclopalladated Pd(II) complexes as thermally stable catalysts can activate aryl bromides and chlorides. These complexes were active and efficient catalysts for the Suzuki–Miyaura reaction of aryl bromides and even less reactive aryl chlorides. The cross‐coupled products of a variety of aryl bromides and aryl chloride with phenylboronic acid in methanol as solvent at 60 °C were produced in excellent yields. Copyright © 2010 John Wiley & Sons, Ltd.     

Improvements in cross coupling reactions of hypervalent siloxane derivatives

[formula: see text] The scope of the palladium-catalyzed cross coupling reaction of aryl halides with phenyltrimethoxysilane has been expanded to include aryl bromides, heteroaryl bromides, and aryl chlorides. A more general Pd(0)-catalyst/ligand system has been developed to activate bromides: palladium(II) acetate (Pd(OAc)2) is activated with triphenylphosphine (PPh3) or tri-o-tolylphosphine (P(o-tol)3) (1:2 molar ratio of Pd:phosphine). Coupling of aryl chloride derivatives required addition of 2-(dicyclohexylphosphino)biphenyl (Buchwald's ligand) to Pd2dba3 (tris-(dibenzylideneacetone)dipalladium(0)) (1:1.5 molar ratio of Pd:phosphine).     

9-fluorenylphosphines for the Pd-catalyzed sonogashira, suzuki, and Buchwald-Hartwig coupling reactions in organic solvents and water

The lithiation/alkylation of fluorene leads to various 9-alkyl-fluorenes (alkyl=Me, Et, iPr, -Pr, -C18H25) in>95% yields, for which lithiation and reaction with R2PCl (R=Cy, iPr, tBu) generates 9-alkyl, 9-PR2-fluorenes which constitute electron-rich and bulky phosphine ligands. The in-situ-formed palladium-phosphine complexes ([Na2PdCl4], phosphonium salt, base, substrates) were tested in the Sonogashira, Suzuki, and Buchwald-Hartwig reactions of aryl chlorides and aryl bromides in organic solvents. The Sonogashira coupling of aryl chlorides at 100-120 degrees C leads to>90% yields with 1 mol% of Pd catalyst. The Suzuki coupling of aryl chlorides typically requires 0.05 mol% of Pd catalyst at 100 degrees C in dioxane for quantitative product formation. To carry out "green" cross-coupling reactions in water, 9-ethylfluorenyldicyclohexylphosphine was reacted in sulphuric acid to generate the respective 2-sulfonated phosphonium salt. The Suzuki coupling of activated aryl chlorides by using this water-soluble catalyst requires only 0.01 mol% of Pd catalyst, while a wide range of aryl chlorides can be quantitatively converted into the respective coupling products by using 0.1-0.5 mol% of catalyst in pure water at 100 degrees C. Difficult substrate combinations, such as naphthylboronic acid or 3-pyridylboronic acid and aryl chlorides are coupled at 100 degrees C by using 0.1-0.5 mol% of catalyst in pure water to obtain the respective N-heterocycles in quantitative yields. The copper-free aqueous Sonogashira coupling of aryl bromides generates the respective tolane derivatives in>95% yield.     

Cascade alkenyl amination/Heck reaction promoted by a bifunctional palladium catalyst: a novel one-pot synthesis of indoles from o-haloanilines and alkenyl halides

A novel approach for the synthesis of the important indole ring is described. Indoles are obtained from o-bromoanilines and alkenyl halides in a Pd-catalyzed cascade process that involves an alkenyl amination followed by an intramolecular Heck reaction. The overall process represents the first example of the participation of alkenyl amination reactions in Pd-catalyzed cascade reactions. Initially, the relative reactivity of aryl and alkenyl bromides and chlorides towards Pd-catalyzed amination was investigated. Competition experiments were carried out in the presence of primary and secondary amines, and these revealed the reactivity order alkenyl bromides > aryl bromides > alkenyl chlorides > aryl chlorides, as well as very high chemoselectivity; the more reactive halide was always favored. Thereafter, optimized reaction conditions for the sequential alkenyl amination/Heck cyclization to give indoles were investigated with the model reaction of o-bromoaniline with alpha-bromostyrene. An extensive screening of ligands, bases, and reaction conditions revealed that the [Pd2(dba)3]/DavePhos, NaOtBu, toluene combination at 100 degrees C were the optimized reaction conditions to carry out the cascade process (dba=dibenzylideneacetone, DavePhos=2-dicyclohexylphosphino-2'-N,N-dimethylaminobiphenyl). The reaction proceeds with aryl, alkyl, and functionalized substitutents in both starting reactants. The cyclization was also studied with N-substituted o-bromoanilines (which would give rise to N-substituted indoles); however, in this case, indole formation occurred only with 1-substituted-2-bromoalkenes. Finally, the application of this methodology to o-chloroanilines required further optimization. Although the catalyst based on DavePhos failed to promote the cascade process, a catalytic combination based on [Pd2(dba)3]/X-Phos promoted the formation of the indole ring also from the less reactive chloroanilines.     

Copper-catalyzed conversion of aryl and heteroaryl bromides into the corresponding chlorides

An efficient method for the synthesis of aryl and heteroaryl chlorides is described. The reactions of aryl and heteroaryl bromides with tetramethylammonium chloride proceeded smoothly in the presence of a copper catalyst under mild reaction conditions to produce the corresponding chlorides in satisfactory to excellent yields.     

Ni(II)/Zn-Mediated chemoselective arylation of aromatic aldehydes: facile synthesis of diaryl carbinols

Direct arylation of aromatic aldehydes with aryl bromides in the presence of Ni(II)/Zn was investigated. The choice of ligand in this nickel-catalyzed coupling was critical to the formation of the secondary alcohols. Monodentate phosphine ligands were ineffective, whereas NiBr(2)(dppe)/Zn successfully catalyzed this reductive coupling reaction. The reaction conditions were mild and diarylcarbinols with a variety of functional groups such as ketone, ester, amide, and nitrile groups were readily prepared.     

Palladium-catalyzed Stille cross-couplings of sulfonyl chlorides and organostannanes

Arene and phenylmethanesulfonyl chlorides can be cross-coupled with aryl, heteroaryl, and alkenylstannanes with desulfitation in the presence of 10 mol % CuBr.Me2S, 1.5 mol % Pd2dba3, and 5 mol % tri-2-furylphosphine in tetrahydrofuran or toluene under reflux. This extension of the Stille cross-coupling reaction realizes a new and economical method for the generation of C-C bonds. The palladium-catalyzed carbonylative Stille cross-coupling reactions of arenesulfonyl chlorides and organostannanes in the presence of CO (60 bar) at 110 degrees C in toluene generate the corresponding ketones. Arenesulfonyl chlorides are more reactive than aryl chlorides and aryl bromides in their Stille cross-coupling with organostannanes but less reactive than aryl iodides. The new methods disclosed for the generation of C-C bonds open new possibilities for medicinal chemistry and material sciences.     

Nickel‐Catalyzed Thiolation of Aryl Halides and Heteroaryl Halides through Electrochemistry

Transition‐metal‐catalyzed coupling reactions are useful tools for synthesizing aryl sulfur compounds. However, conventional transition‐metal‐catalyzed thiolation of aryl bromides and chlorides typically requires the use of strong base under elevated reaction temperature. Herein, we report the first examples of nickel‐catalyzed electrochemical thiolation of aryl bromides and chlorides in the absence of an external base at room temperature using undivided electrochemical cells.     

Palladium-catalyzed tetrakis(dimethylamino)ethylene-promoted reductive coupling of aryl halides

Tetrakis(dimethylamino)ethylene (TDAE)/cat. PdCl(2)(PhCN)(2)-promoted reductive coupling of aryl bromides having either electron-donating or electron-withdrawing groups on their para- and/or meta-position proceeded smoothly to afford the corresponding biaryls in good to excellent yields. Notably, TDAE is such a mild reductant that easily reducible groups, such as carbonyl and nitro groups, are tolerate. A similar reductive coupling of ortho-substituted aryl bromides did not occur at all. The proper choice of palladium catalysts is essential for the reductive coupling; thus, PdCl(2)(PhCN)(2), PdCl(2)(MeCN)(2), Pd(hfacac)(2), Pd(2)(dba)(3), PdCl(2), and Pd(OAc)(2) were used successively for this reaction, but phosphine-ligated palladium catalysts such as Pd(PPh(3))(4), PdCl(2)(PPh(3))(2), and Pd(dppp) did not promote the reaction. The reductive coupling did not occur with nickel catalysts such as NiBr(2), NiCl(2)(bpy), and Ni(acac)(2). The TDAE/cat. palladium-promoted reductive coupling of aryl halides having electron-withdrawing groups took place more efficiently than that of aryl halides substituted with electron-donating groups. A plausible mechanism of TDAE/cat. palladium-promoted reaction is discussed.     

Expanding the scope of the Cu assisted Suzuki-Miyaura reaction

Recent advances in the development of the copper facilitated Suzuki-Miyaura reaction are described. Improvements include expansion of substrate scope to include aryl chlorides and polyhalo aryl boronates. It was found that use of S-Phos and X-Phos could accomplish the coupling of 2-pyridyl boronates to aryl chlorides and bromides in shorter reaction times and in higher yield than previously described with DPPF.     

Efficient Stille cross-coupling reaction catalyzed by the Pd(OAc)2/Dabco catalytic system

[reaction: see text] An efficient Pd(OAc)2/Dabco-catalyzed Stille cross-coupling reaction procedure has been developed. In the presence of Pd(OAc)2 and Dabco (triethylenediamine), various aryl halides including aryl iodides, aryl bromides, and activated aryl chlorides were coupled efficiently with organotin compounds to afford the corresponding biaryls, alkene, and alkynes in good to excellent yields. Furthermore, high TONs [turnover numbers, up to 980,000 TONs for the coupling reaction of 1-bromo-4-nitrobenzene and furan-2-yltributyltin] for the Stille cross-coupling reaction were observed.     

Modified (NHC)Pd(allyl)Cl (NHC = N-heterocyclic carbene) complexes for room-temperature Suzuki-Miyaura and Buchwald-Hartwig reactions

A series of (NHC)Pd(R-allyl)Cl complexes [NHC: IPr = N,N'-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, SIPr = N,N'-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene; R = H, Me, gem-Me2, Ph] have been synthesized and fully characterized. When compared to (NHC)Pd(allyl)Cl, substitution at the terminal position of the allyl scaffold favors a more facile activation step. This translates into higher catalytic activity in the Suzuki-Miyaura and Buchwald-Hartwig reactions, allowing for the coupling of unactivated aryl chlorides at room temperature in minutes. In the Suzuki-Miyaura reaction, aryl triflates, bromides, and chlorides react with boronic acids using very low catalyst loading. In the N-aryl amination reaction, a wide range of substrates has been coupled efficiently; primary-, secondary-, alkyl-, or aryl-amines react in high yields with unactivated, neutral, and activated aryl chlorides and bromides. In both reactions, extremely hindered substrates such as tri-ortho-substituted biaryls and tetra-ortho-substituted diarylamines can be produced without loss of activity. Finally, the present catalytic system has proven to be efficient with as low as 10 parts-per-million (ppm) of precatalyst in the Buchwald-Hartwig reaction and 50 ppm in the Suzuki-Miyaura reaction.     

Palladium-catalyzed cross-coupling of pyrrole anions with aryl chlorides, bromides, and iodides

[reaction: see text] A general method for the conversion of pyrrole anions to 2-arylpyrroles has been developed. Using a palladium precatalyst and sterically demanding 2-(dialkylphosphino)biphenyl ligands, (pyrrolyl)zinc chloride may be cross-coupled with a wide range of aryl halides, including aryl chlorides and aryl bromides, at low catalyst loadings and under mild conditions. A high degree of steric hindrance is tolerated. Certain ring-substituted pyrrole anions have also been arylated with aryl bromide substrates.     

Pd(OAc)2/DABCO-catalyzed Suzuki-Miyaura cross-coupling reaction in DMF

The scope and limitations of the Pd(OAc)₂/DABCO (1,4-diaza-bicyclo[2.2.2]octane)-catalyzed Suzuki-Miyaura cross-coupling reactions have been demonstrated. The results showed that the effect of solvent had a fundamental influence on the reaction. In the presence of Pd(OAc)₂ and DABCO, both aryl bromides and aryl chlorides all worked well with arylboronic acids to form biaryls, heteroaryl-aryls, and biheteroaryls in moderate to excellent yields using DMF as the solvent. Additionally, the reactions of aryl bromides were conducted under relatively mild conditions.