An efficient and general method for the Heck and Buchwald-Hartwig coupling reactions of aryl chlorides

The β-diketiminatophosphane Pd complex acted as a powerful catalyst for the Heck coupling of aryl chlorides with alkenes. Various aryl and heteroaryl chlorides were coupled efficiently under relatively mild conditions. Furthermore, this catalytic system also proved to be highly active in the Buchwald-Hartwig coupling of deactivated and sterically hindered aryl chlorides at room temperature.     

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.     

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.     

A surprisingly mild and versatile method for palladium-catalyzed Suzuki cross-couplings of aryl chlorides in the presence of a triarylphosphine

In the presence of new air-stable triarylphosphine 2, palladium-catalyzed Suzuki reactions of a wide array of aryl chlorides can be accomplished in uniformly good yield, including couplings of very sterically demanding and electronically deactivated substrates; activated aryl chlorides can be coupled at room temperature. In terms of scope and mildness, Pd-2 compares well with other catalyst systems that have been described for Suzuki reactions of aryl chlorides, thereby establishing that triarylphosphines should be regarded as fertile ground for future ligand-design efforts for palladium-catalyzed couplings of aryl chlorides.     

A general and efficient method for the palladium-catalyzed cross-coupling of thiols and secondary phosphines

The general and efficient cross-coupling of thiols with aryl halides was developed utilizing Pd(OAc)₂/1,1′-bis(diisopropylphosphino)ferrocene as the catalyst. The substrate scope is broad and includes a variety of aryl bromides and chlorides, which can be coupled to aliphatic and aromatic thiols. This catalyst system has the widest substrate scope of any reported to date. The present catalyst system also enables the palladium-catalyzed coupling of secondary phosphines with aryl bromides and chlorides.     

Highly effective activation of aryl chlorides for Suzuki coupling in aqueous media using a ferrocene-based Pd(II)–diimine catalyst

The Suzuki coupling of aryl chlorides with boronic acids using a ferrocene-containing Pd(II)–diimine complex as catalyst, in aqueous media, under microwave heating is reported. A small amount of the catalyst (0.1%) was found to be highly effective for coupling unactivated aryl chlorides with boronic acids to form sterically hindered ortho-substituted biaryls. The same catalyst also enabled the coupling of aryl bromides and iodides with various boronic acids in very high yields. The catalyst is air stable and the catalytic reaction can be completed in 15 min.     

Manganese-catalyzed oxidative homo-coupling of aryl Grignard chlorides

Manganese-catalyzed homo-coupling of aryl magnesium chlorides to give biphenyls was successfully achieved using manganese chloride as catalyst. A variety of aryl magnesium chlorides were efficiently converted into the corresponding symmetrical biaryls using 10 mol% MnCl₂ as catalyst in the presence of a stoichiometric amount of 1,2-dichloroethane. Since the aryl chlorides, from which the Grignard reagents were prepared, are cheaper and more readily available that the corresponding bromides and iodides this procedure should become the method of choice for preparing symmetrical biaryls.     

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.     

Pd2(dba)3/P(i-BuNCH2CH2)3N-catalyzed Stille cross-coupling of aryl chlorides

[reaction: see text] The Pd(2)(dba)(3)/P(i-BuNCH(2)CH(2))(3)N (1d) catalyst system is highly effective for the Stille cross-coupling of aryl chlorides with organotin compounds. This method represents only the second general method for the coupling of aryl chlorides. Other proazaphosphatranes possessing benzyl substituents also generate very active catalysts for Stille reactions. Noteworthy features of the method are: (a) commercial availability of ligand 1d, (b) the wide array of aryl chlorides that can be coupled, and (c) applicability to aryl, vinyl, and allyl tin reagents.     

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.     

Palladium on carbon as a precatalyst for the Suzuki-Miyuara cross-coupling of aryl chlorides

Palladium on carbon is used as a precatalyst for Suzuki-Miyaura reaction of aryl chlorides and aryl boronic acids. An efficient catalyst system is obtained that allows the reaction of substrates that are difficult to couple under ligand free conditions. This includes electron rich and sterically hindered aryl chlorides as well as electron deficient and sterically hindered boronic acids. We have discovered that the amount of ligand needed to catalyze these reactions can be significantly decreased by incorporating an incubation period. This study also provides valuable insight into the mechanism of the Pd/C-catalyzed Suzuki-Miyaura cross-coupling. For example, mercury poisoning studies provide evidence that the active catalytic species is homogeneous. However, catalyst reuse and low metal contamination indicate that this system retains many of the advantages of a heterogeneous catalyst. From these results, a catalytic cycle is proposed.     

Room temperature Pd(0)/Ad3P-catalyzed coupling reactions of aryl chlorides with bis(pinacolato)diboron

Room temperature Pd(0)/Ad₃P-catalyzed cross-coupling reactions of aryl chlorides with bis(pinacolato)diboron are described. The Pd(0)/Ad₃P catalyst, generated from Ad₃P-coordinated acetanilide-based palladacycle complex, proved to be an efficient catalyst system for the Miyaura borylation reactions of a variety of aryl chlorides with bis(pinacolato)diboron. The mild reaction condition, the easy availability of the catalyst and good coupling yields make these reactions potentially useful in organic synthesis.     

Highly reactive, general and long-lived catalysts for palladium-catalyzed amination of heteroaryl and aryl chlorides, bromides, and iodides: scope and structure-activity relationships

We describe a systematic study of the scope and relationship between ligand structure and activity for a highly efficient and selective class of catalysts containing sterically hindered chelating alkylphosphines for the amination of heteroaryl and aryl chlorides, bromides, and iodides. In the presence of this catalyst, aryl and heteroaryl chlorides, bromides, and iodides react with many primary amines in high yields with part-per-million quantities of palladium precursor and ligand. Many reactions of primary amines with both heteroaryl and aryl chlorides, bromides, and iodides occur to completion with 0.0005-0.05 mol % catalyst. A comparison of the reactivity of this catalyst for the coupling of primary amines at these loadings is made with catalysts generated from hindered monophosphines and carbenes, and these data illustrate the benefits of chelation. Studies on structural variants of the most active catalyst indicate that a rigid backbone in the bidentate structure, strong electron donation, and severe hindrance all contribute to its high reactivity. Thus, these complexes constitute a fourth-generation catalyst for the amination of aryl halides, whose activity complements catalysts based on monophosphines and carbenes.     

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.     

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.     

Electron transfer activity of a cobalt crown carbene complex

The novel cobalt(II) crown carbene complex 12(II) has been prepared and characterised by X-ray crystallography. This complex is reduced in a one-electron process to a cobalt(I) complex that acts as a powerful single electron donor, reducing aryl halides, including aryl chlorides and demonstrating the strong electron-enriching effect on cobalt of the crown carbene ligand. The metal ion is tightly held in a tetrahedral conformation by its enveloping crown ligand—this prevents what would otherwise be expected to be an easy oxidation to cobalt(III) under standard electrochemical conditions. Complex 12 is shown to be an effective catalyst in mediated electrochemical reductions of aryl iodides at room temperature and aryl bromides at 90 °C. The electrochemically produced catalyst [from 10 mol % of added Co(II) complex] also triggers reduction of aryl chlorides, although this seems at the limit of its reactivity. However, when the cobalt(II) complex is reduced by sodium amalgam, this affords stoichiometric quantities of the active cobalt reducing agent, which affords reduction of aryl iodides and bromides as above, but also reduces aryl chlorides at elevated temperatures.     

A General Palladium‐Catalyzed Hiyama Cross‐Coupling Reaction of Aryl and Heteroaryl Chlorides

A general palladium‐catalyzed Hiyama cross‐coupling reaction of aryl and heteroaryl chlorides with aryl and heteroaryl trialkoxysilanes by a Pd(OAc)₂/ L2 catalytic system is presented. A newly developed water addition protocol can dramatically improve the product yields. The conjugation of the Pd/ L2 system and the water addition protocol can efficiently catalyze a broad range of electron‐rich, ‐neutral, ‐deficient, and sterically hindered aryl chlorides and heteroaryl chlorides with excellent yields within three hours and the catalyst loading can be down to 0.05 mol % Pd for the first time. Hiyama coupling of heteroaryl chlorides with heteroaryl silanes is also reported for the first time. The reaction can be easily scaled up 200 times (100 mmol) without any degasification and purification of reactants; this facilitates the practical application in routine synthesis.     

环钯-[PPh4]Br体系催化氯代芳烃的Heck芳基化反应研究

以氯代芳烃为底物，季鏻盐[PPh4]Br为助催化剂，用于环钯催化的Heek芳基化反应．结果表明，在环钯-[PPh4]Br催化体系中，以Na2CO3作为碱性试剂，使用0．3mol％Pd的环钯催化剂催化氯苯的Heek反应，就可得到比较高的产率（88％）和转化率（90％）．对于大部分卤代芳烃Heck反应而言，环钯-[PPh4]Br是一种有效的催化体系，即使是对含推电子基团的不活泼的氯代芳烃，在此体系中也能获得比较好的结果．此外，文中还探讨了反应温度、[PPh4]Br／Pd比值及催化剂回用对反应活性的影响．     

Palladium-catalyzed indole, pyrrole, and furan arylation by aryl chlorides

The palladium-catalyzed direct arylation of indoles, pyrroles, and furans by aryl chlorides has been demonstrated. The method employs a palladium acetate catalyst, 2-(dicyclohexylphosphino)-biphenyl ligand, and an inorganic base. Electron-rich and electron-poor aryl chlorides as well as chloropyridine coupling partners can be used, and arylated heterocycles are obtained in moderate to good yields. Optimization of base, ligand, and solvent is required for achieving best results.     

An efficient system for the Pd-catalyzed cross-coupling of amides and aryl chlorides

A catalyst based on a new biarylphosphine ligand (3) for the Pd-catalyzed cross-coupling reactions of amides and aryl chlorides is described. This system shows the highest turnover frequencies reported to date for these reactions, especially for aryl chloride substrates bearing an ortho substituent. An array of amides and aryl chlorides were successfully reacted in good to excellent yields.