Monoligated palladium species as catalysts in cross-coupling reactions

Palladium-mediated cross-coupling reactions are attractive organometallic transformations for the generation of C--C, C--N, C--O, and C--S bonds. Despite being widely employed in small-scale syntheses, cross-coupling reactions have not found important industrial applications because until recently, only reactive aryl bromides and iodides could be used as substrates. These substrates are generally more expensive and less widely available than their chloride counterparts. Over the past few years, new catalytic systems with the ability to activate unreactive and sterically hindered aryl chlorides have been developed. The new catalysts are based on palladium complexes that contain electron-rich and bulky phosphine or carbene ligands. The enhanced reactivity observed with these new systems has been attributed to the formation of unsaturated and reactive [PdL] species which can readily undergo oxidative addition reactions with ArX to yield [Pd(Ar)X(L)].     

Ligand-supported palladium-catalyzed cross-coupling reactions of (hetero) aryl chlorides

The introduction of electron rich and sterically hindered ligands has made otherwise inert aryl chlorides and hetero aryl chlorides viable coupling partners in palladium-catalyzed Suzuki-Miyaura, Sonogashira, Stille and other types of cross-coupling reactions. This review gives highlights of cross-coupling of aryl chlorides employing in situ generated palladium catalytic systems.     

Improved studies of cross‐coupling reactions of 5‐(tri‐n‐butystannyl)‐ and 5,5′‐bis(tri‐n‐butylstannyl)‐2,2′‐bithiophene with aryl halides

Stille coupling under standard conditions proceeds in low yield when using hindered organostannanes (1) or (2) and aryl bromide partners. The inclusion of aryl iodide instead of aryl bromide with the same organostannanes, significantly improves the efficiency of the coupling, providing a variety of desired products in good to excellent yield. The yields of Stille coupling are compared to the different reactivity of aryl halides. This study of Stille coupling with different aryl halides are documented and rationalized.     

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.     

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.     

Organometallic alkylation of 2-chloro-4,6-dimethoxy-1,3,5-triazine: a study

The reactivity of 2-chloro-4,6-dimethoxy-1,3,5-triazine (1) has been investigated in Pd- or Ni-catalyzed cross-coupling processes with organostannanes, Grignard reagents, organoalanes and organozinc halides. All organometallic reagents considered form new C-C bonds on the heteroaromatic ring and afford the corresponding 2-alkyl-4,6-dimethoxy-1,3,5-triazines in moderate to very good yields. The collected data allows the choice of the alkylating agent as well as the experimental conditions depending on the residue to transfer.     

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.     

Cross-coupling reactions of aryl and vinyl chlorides catalyzed by a palladium complex derived from an air-stable H-phosphonate

A palladium complex derived from air-stable TADDOLP(O)H catalyzes efficiently Hiyama, Stille, Kumada and Suzuki cross-coupling reactions of aryl and vinyl chlorides.     

Reusable copper-catalyzed cross-coupling reactions of aryl halides with organotins in inexpensive ionic liquids

A combination of Cu2O nanoparticles with P(o-tol)3 shows highly catalytic activity for the Stille cross-coupling reaction. A series of copper catalysts and ligands were evaluated, and Cu2O nanoparticles combined with P(o-tol)3 provided the best results. In the presence of Cu2O nanoparticles and P(o-tol)3, a variety of aryl halides including aryl chlorides underwent the Stille reaction with organotins smoothly in moderate to excellent yields using inexpensive TBAB (n-Bu4NBr) as the medium. It is noteworthy that the Cu2O/P(o-tol)3/TBAB system can be recovered and reused at least three times without any loss of catalytic activity among the reactions of aryl iodides and activated aryl bromides.     

Suzuki-Miyaura, alpha-ketone arylation and dehalogenation reactions catalyzed by a versatile N-heterocyclic carbene-palladacycle complex

[reaction: see text] The activity of the complex (IPr)PdCl(eta2-N,C-C12H7NMe2), 1 [IPr = (N,N'-bis(2,6-diisopropylphenyl)imidazol)-2-ylidene], in the Suzuki-Miyaura cross-coupling reaction involving unactivated aryl chlorides and triflates with arylboronic acids at room temperature in technical grade 2-propanol is described. These conditions allow for the synthesis of di- and tri-ortho-substituted biaryls in very short reaction times. This complex also displays very high activity for alpha-ketone arylation and dehalogenation reactions of activated and unactivated aryl chlorides.     

Room-Temperature Arylation of Thiols: Breakthrough with Aryl Chlorides

The formation of aryl C−S bonds is an important chemical transformation because aryl sulfides are valuable building blocks for the synthesis of biologically and pharmaceutically active molecules and organic materials. Aryl sulfides have traditionally been synthesized through the transition-metal-catalyzed cross-coupling of aryl halides with thiols. However, the aryl halides used are usually bromides and iodides; readily available, low-cost aryl chlorides often not reactive enough. Furthermore, the deactivation of transition-metal catalysts by thiols has forced chemists to use high catalyst loadings, specially designed ligands, high temperatures, and/or strong bases, thus leading to high costs and the incompatibility of some functional groups. Herein, we describe a simple and efficient visible-light photoredox arylation of thiols with aryl halides at room temperature. More importantly, various aryl chlorides are also effective arylation reagents under the present conditions.     

Dendrimer-encapsulated Pd nanoparticles as aqueous, room-temperature catalysts for the Stille reaction

We report that dendrimer-encapsulated Pd nanoparticles having a diameter of approximately 1.7 nm are effective and general catalysts for coupling aryl halides to organostannanes (the Stille reaction) under mild conditions. The significant results of this study are that the Stille reaction is catalyzed by dendrimer-encapsulated Pd nanoparticles in very good yield, in aqueous solution at 23 degrees C, and using only 0.100 atom % of Pd as catalyst.     

Copper(I)-only catalyzed reactions of (E)-2,3-difluoro-3-stannylacrylic ester with acid chlorides and mechanistic studies of the "copper effect" in stille coupling reactions

[reaction: see text] The reactions of (E)-2,3-difluoro-3-stannylacrylic ester with acid chlorides under catalysis of CuI stereospecifically afforded ethyl (2Z)-2,3-difluoro-4-oxo-substituted 2-butenoates in good yields. Moreover, direct spectroscopic observation of the corresponding organocopper reagent was observed for the first time in Stille coupling reactions of organostannanes.     

Efficient Stille cross-coupling reaction using aryl chlorides or bromides in water

An efficient Stille cross-coupling reaction using a variety of aryl halides in neat water has been developed. Employing palladium-phosphinous acid catalyst [(t-Bu)(2)P(OH)](2)PdCl(2) allows formation of biaryls from aryl chlorides and bromides in good to high yields. Functional groups such as ketones and nitriles are tolerated, and organic cosolvents are not required. The air stability and solubility in water of the palladium complexes used in this study facilitate operation of the coupling reaction and product isolation. The feasibility of catalyst recycling has also been demonstrated.     

Atom-efficient metal-catalyzed cross-coupling reaction of indium organometallics with organic electrophiles.

The novel metal-catalyzed cross-coupling reaction of indium organometallics with organic electrophiles is described. Triorganoindium compounds (R(3)In) containing alkyl, vinyl, aryl, and alkynyl groups are efficiently prepared from the corresponding lithium or magnesium organometallics by reaction with indium trichloride. The cross-coupling reaction of R(3)In with aryl halides and pseudohalides (iodide 2, bromide 5, and triflate 4), vinyl triflates, benzyl bromides, and acid chlorides proceeds under palladium catalysis in excellent yields and with high chemoselectivity. Indium organometallics also react with aryl chlorides as under nickel catalysis. In the cross-coupling reaction the triorganoindium compounds transfer, in a clear example of atom economy, all three of the organic groups attached to the metal, as shown by the necessity of using only 34 mol % of indium. The feasibility of using R(3)In in reactions with different electrophiles, along with the high yields and chemoselectivities obtained, reveals indium organometallics to be useful alternatives to other organometallics in cross-coupling reactions.     

Palladium-mediated functionalization of heteroaromatic cations: comparative study on quinolizinium cations

An efficient palladium-catalyzed cross-coupling reaction on heteroaromatic cations is described. A comparative study of the Stille and Suzuki reactions shows that only the Stille reaction is able to produce an efficient C-C bond formation between any of the four isomeric bromoquinolizinium bromides and a variety of stannanes. In the presence of the catalysts Pd(PPh3)4 or Pd2(dba)3P(o-Tol)3, vinyl, ethynyl, aryl, and heteroaryl groups are successfully incorporated into the quinolizinium system in satisfactory yields under mild reaction conditions. This procedure represents a marked improvement on the functionalization of this class of heteroaromatic cation.     

Au(I) /Au(III) catalysis: an alternative approach for C-C oxidative coupling

When reacted in the presence of external oxidants, gold complexes are capable of catalyzing oxidative homo- and cross-coupling reactions involving the formation of new C-C bonds. Over the last few years, several cascade processes have been reported in which coupling is preceded by a gold-mediated aryl C-H functionalization or nucleophilic addition. These reactions combine the unique reactivity of gold with oxidative coupling, enabling the construction of C-C bonds between coupling partners that are not easily accessed using alternative catalysts. In this Concept paper, the development of gold-catalyzed oxidative coupling reactions is discussed focusing on C-C bond-forming reactions of broad synthetic appeal.     

Palladium-Catalyzed Coupling of Organo-Stannanes with Hypervalent Iodonium Salts

The palladium-catalyzed cross-coupling of organostannanes with iodonium salts in the presence of PdCl₂(0.5 mol %) or Pd/C(2 mol %) as Pd(O) source was accomplished at room temperature under aqueous conditions.     

Coupling Reactions of Alkynylsilanes Mediated by a Cu(I) Salt: Novel Syntheses of Conjugate Diynes and Disubstituted Ethynes

Reaction of 1-trimethylsilylalkyne with copper(I) chloride in a polar solvent, DMF, at 60 degrees C under an aerobic conditions smoothly undergoes homo-coupling to give the corresponding symmetrical 1,3-butadiynes in 70-99% yields. In addition, (arylethynyl)trimethylsilanes are found to couple with aryl triflates and chlorides in the presence of Cu(I)/Pd(0) (10 mol %/5 or 10 mol %) cocatalyst system to give the corresponding diarylethynes in 49-99% yields. The cross-coupling reaction is applied to a one-pot synthesis of the corresponding unsymmetrical diarylethynes from (trimethylsilyl)ethyne via sequential Sonogashira-Hagihara and the present cross-coupling reactions using two different aryl triflates. The reactions of (arylethynyl)trimethylsilanes with aryl(chloro)ethynes in the presence of 10 mol % of CuCl also yield the corresponding unsymmetrical 1,3-butadiynes in 43-97% yields.