Selected Copper‐Based Reactions for C−N,C−O,C−S,and C−C Bond Formation

Metal‐catalyzed cross‐coupling reactions belong to the most important transformations in organic synthesis. Copper catalysis has received great attention owing to the low toxicity and low cost of copper. However, traditional Ullmann‐type couplings suffer from limited substrate scopes and harsh reaction conditions. The introduction of several bidentate ligands, such as amino acids, diamines, 1,3‐diketones, and oxalic diamides, over the past two decades has totally changed this situation as these ligands enable the copper‐catalyzed coupling of aryl halides and nucleophiles at both low reaction temperatures and catalyst loadings. The reaction scope has also been greatly expanded, rendering this copper‐based cross‐coupling attractive for both academia and industry. In this Review, we have summarized the latest progress in the development of useful reaction conditions for the coupling of (hetero)aryl halides with different nucleophiles. Additionally, recent advances in copper‐catalyzed coupling reactions with aryl boronates and the copper‐based trifluoromethylation of aromatic electrophiles will be discussed.     

Amino acid promoted CuI-catalyzed C-N bond formation between aryl halides and amines or N-containing heterocycles

CuI-catalyzed coupling reaction of electron-deficient aryl iodides with aliphatic primary amines occurs at 40 degrees C under the promotion of N-methylglycine. Using l-proline as the promoter, coupling reaction of aryl iodides or aryl bromides with aliphatic primary amines, aliphatic cyclic secondary amines, or electron-rich primary arylamines proceeds at 60-90 degrees C; an intramolecular coupling reaction between aryl chloride and primary amine moieties gives indoline at 70 degrees C; coupling reaction of aryl iodides with indole, pyrrole, carbazole, imidazole, or pyrazole can be carried out at 75-90 degrees C; and coupling reaction of electron-deficient aryl bromides with imidazole or pyrazole occurs at 60-90 degrees C to provide the corresponding N-aryl products in good to excellent yields. In addition, N,N-dimethylglycine promotes the coupling reaction of electron-rich aryl bromides with imidazole or pyrazole to afford the corresponding N-aryl imidazoles or pyrazoles at 110 degrees C. The possible action of amino acids in these coupling reactions is discussed.     

A novel efficient method for synthesis of propargylamines via three-component coupling of aryl azide, aldehyde, and alkyne promoted by iron-iodine-copper(I) bromide

A novel, efficient method has been developed for the synthesis of propargylamines through a three-component coupling of aryl azides, aldehydes, and alkynes in the presence of iron-iodine-copper(I) bromide as catalyst. This method is the first example for directly using aryl azides as an amino component in a three-component coupling reaction. Some of the major advantages of this protocol are: good yields, the involvement of a less-expensive and non-toxic catalyst, mild reaction conditions, and a wide range of substrates.     

迭代Suzuki偶联反应合成全氟环丁基芳基醚齐聚物的研究

对迭代Suzuki偶联反应合成全氟环丁基芳基醚齐聚物的方法进行了研究, 并合成了全氟环丁基芳基醚齐聚物. 首先从对溴苯酚出发, 合成了含有一个全氟环丁基芳基醚结构单元的中间体3. 芳基硼酸与中间体3进行Suzuki偶联反应, 得到了含有一个全氟环丁基芳基醚结构单元的硼酸. 重复与中间体3进行Suzuki偶联反应, 从而合成了全氟环丁基芳基醚二聚体和三聚体. 最后通过热环化二聚反应合成了全氟环丁基芳基醚三聚体、五聚体和七聚体.     

Vinyldisiloxanes: their synthesis, cross coupling and applications

During the studies towards the development of pentafluorophenyldimethylsilanes as a novel organosilicon cross coupling reagent it was revealed that the active silanolate and the corresponding disiloxane formed rapidly under basic conditions. The discovery that disiloxanes are in equilibrium with the silanolate led to the use of disiloxanes as cross coupling partners under fluoride free conditions. Our previous report focused on the synthesis and base induced cross coupling of aryl substituted vinyldisiloxanes with aryl halides; good yields and selectivities were achieved. As a continuation of our research, studies into the factors which influence the successful outcome of the cross coupling reaction with both alkyl and aryl substituted vinyldisiloxanes were examined and a proposed mechanism discussed. Further investigation into expanding the breadth and diversity of substituted vinyldisiloxanes in cross coupling was explored and applied to the synthesis of unsymmetrical trans-stilbenes and cyclic structures containing the trans-alkene architecture.     

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.     

Rapid and efficient Pd-catalyzed Sonogashira coupling of aryl chlorides

An efficient and effective microwave-assisted cross-coupling of terminal alkynes with various aryl chlorides including sterically hindered, electron-rich, electron-neutral, and electron-deficient aryl chloride is developed. It proceeds faster and generally gives good to excellent yields and also can be extended successfully to the Suzuki coupling and Buchwald-Hartwig amination, as well as the Heck coupling with inert aryl chlorides. The short reaction times and simple reaction conditions coupling with a broad substrate scope render this method particularly attractive for the efficient preparation of biologically and medicinally interesting molecules.     

An efficient,regio- and stereoselective palladium-catalyzed route to tetrasubstituted olefins

An efficient, regio- and stereoselective palladium-catalyzed route to tetrasubstituted olefins has been developed, which involves the intermolecular coupling of an aryl iodide, an internal alkyne, and an arylboronic acid. The reaction involves cis-addition of the aryl group from the aryl halide to the less hindered or less electron-poor end of the alkyne, while the aryl group from the arylboronic acid adds to the other end. [reaction: see text]     

Synthesis of symmetrical and unsymmetrical N,N'-diaryl guanidines via copper/N-methylglycine-catalyzed arylation of guanidine nitrate

CuI/N-methylglycine-catalyzed coupling reaction of guanidine nitrate with both aryl iodides and bromides takes place at 70-100 °C, affording symmetrical N,N'-diaryl guanidines with good to excellent yields. Unsymmetrical N,N'-diaryl guanidines can be assembled via monoarylation of guanidine nitrate with aryl iodides bearing a strong electron-withdrawing group and subsequent coupling with another aryl iodide.     

Single‐Electron‐Transfer‐Induced Coupling of Arylzinc Reagents with Aryl and Alkenyl Halides

Arylzinc reagents, prepared from aryl halides/zinc powder or aryl Grignard reagents/zinc chloride, were found to undergo coupling with aryl and alkenyl halides without the aid of transition‐metal catalysis to give biaryls and styrene derivatives, respectively. In this context, we have already reported the corresponding reaction using aryl Grignard reagents instead of arylzinc reagents. Compared with the Grignard cross‐coupling, the present reaction features high functional‐group tolerance, whereby electrophilic groups such as alkoxycarbonyl and cyano groups are compatible as substituents on both the arylzinc reagents and the aryl halides. Aryl halides receive a single electron and thereby become activated as the corresponding anion radicals, which react with arylzinc reagents, thus leading to the cross‐coupling products.     

Bis-diimidazolylidine complexes of nickel: investigations into nickel catalyzed coupling reactions

Air and moisture stable homoleptic bis(diimidazolylidine)nickel(II) complexes, ([(diNHC)(2)Ni](2+)) 3a,b and their corresponding silver(I) 4a,b and palladium(II) 5a,b complexes were synthesized and characterized by NMR and single crystal X-ray analysis. The catalytic potential of complex 3a was assessed in Mizoroki-Heck and Suzuki-Miyaura coupling reactions. In the Suzuki-Miyaura coupling reaction, nickel precatalyst 3a was active for the coupling of aryl chlorides as well as aryl fluorides. The analogously synthesized Pd(II) complexes resulted in formation of (diNHC)PdCl(2) species which were not active for the coupling of aryl fluorides. For the Mizoroki-Heck reaction, it was found that aryl iodides could be activated in the absence of nickel or palladium precatalysts when using Na(2)CO(3) or NEt(3) as base while aryl iodides and aryl bromides could be activated in the Suzuki-Miyaura reaction sans precatalyst when K(3)PO(4) was used as base.     

Methionine: a green and efficient promoter for copper‐catalyzed Sonogashira cross‐coupling reactions

In the presence of amino acids as environmentally friendly ligands, CuI‐catalyzed Sonogashira cross‐coupling of various aryl halides with phenylacetylene was conducted to afford the corresponding internal alkynes. l ‐Methionine was found to be useful for this palladium‐free and amine‐free coupling reaction. It was also found that the solvent system plays an important role in this reaction, and significantly affects the product formation and reaction rate. Sonogashira coupling of aryl iodides and aryl bromides in dimethylsulfoxide or dimethylformamide gave the coupled products in good to excellent yields. Copyright © 2015 John Wiley & Sons, Ltd.     

Mono- and beta,beta-double-Heck reactions of alpha,beta-unsaturated carbonyl compounds in aqueous media

Optimized reaction conditions for the mono- and beta,beta-diarylation of electron-deficient alkenes in aqueous media catalyzed either by a p-hydroxyacetophenone oxime-derived palladacycle or by palladium(II) acetate under phosphine-free conditions and in the presence of (dicyclohexyl)methylamine as base are described. Regioselective monoarylation of unsubstituted and substituted alpha,beta-unsaturated carbonyl compounds takes place with aryl iodides at 120 degrees C in water. Aqueous N,N-dimethylacetamide (DMA), tetra-n-butylammonium bromide (TBAB) as additive, and the palladacycle as catalyst are the most efficient conditions for the coupling with aryl bromides, good stereoselectivities being also obtained in the arylation of crotonates and itaconates, whereas cinnamic derivatives afford lower steroselectivity, with the exception of cinnamic acid and nitrile. beta,beta-Diarylation of unsubstituted alpha,beta-unsaturated carbonyl compounds can be controlled by using higher loading of the palladacycle and can be performed in refluxing water for aryl iodides, whereas DMA must be used for aryl bromides. Microwave irradiation can be used in the monoarylation of tert-butyl acrylate with aryl iodides in water or the coupling between ethyl cinnamate and aryl bromides in aqueous DMA.     

Synthesis of 6H-dibenzo[b,d]pyran-6-ones from aryl 3-bromopropenoates via a sequential one-pot procedure using the Sonogashira coupling-benzannulation reaction

Various kinds of 6H-dibenzo[b,d]pyran-6-ones 4 were synthesized via a sequential one-pot procedure using the Sonogashira coupling-benzannulation reaction of aryl 3-bromopropenoates 1, in which the ortho-position of aryl group is substituted with enynes or iodine, with acetylenes 2 in the presence of palladium and copper catalysts. The Sonogashira coupling between the aryl 3-bromopropenoates 1a and 1b, bearing enynes at the ortho-position of aryl group, and alkynes 2a-g gave the enyne intermediates 3 in situ, which subsequently underwent the palladium-catalyzed benzannulation reaction to afford the 6H-dibenzo[b,d]pyran-6-ones 5a-g and 6. The Sonogashira coupling between the aryl 3-bromopropenoate 1c, bearing iodine at the ortho-position of aryl group, and diynes 2f and 2h produced the diyne intermediates 13, which underwent the benzannulation reaction to afford the 6H-dibenzo[b,d]pyran-6-ones 14f and 14h.     

Cross‐Coupling of Sodium Sulfinates with Aryl,Heteroaryl, and Vinyl Halides by Nickel/Photoredox Dual Catalysis

An efficient photoredox/nickel catalyzed sulfonylation reaction of aryl, heteroaryl, and vinyl halides has been achieved for the first time. This newly developed sulfonylation protocol provides a versatile method for the synthesis of diverse aromatic sulfones at room temperature and shows excellent functional group tolerance. The electrophilic coupling partners are not limited to aryl, heteroaryl, and vinyl bromides and iodides, but also includes less reactive aryl chlorides as suitable substrates for this transformation.     

Cross‐Coupling of Sodium Sulfinates with Aryl,Heteroaryl, and Vinyl Halides by Nickel/Photoredox Dual Catalysis

An efficient photoredox/nickel catalyzed sulfonylation reaction of aryl, heteroaryl, and vinyl halides has been achieved for the first time. This newly developed sulfonylation protocol provides a versatile method for the synthesis of diverse aromatic sulfones at room temperature and shows excellent functional group tolerance. The electrophilic coupling partners are not limited to aryl, heteroaryl, and vinyl bromides and iodides, but also includes less reactive aryl chlorides as suitable substrates for this transformation.     

Rapid, easy copper-free Sonogashira couplings using aryl iodides and activated aryl bromides

We present here an easy, rapid copper-free methodology for the Sonogashira coupling reaction. It works well for a range of aryl iodides and activated aryl bromides.     

钯催化偶联-消去法合成芳基末端炔的研究进展

钯催化偶联-消去法合成芳基末端炔的研究进展;芳炔;偶联反应;钯催化剂;合成;综述     

Palladium-catalyzed aminosulfonylation of aryl halides

The palladium-catalyzed three-component coupling of aryl iodides, sulfur dioxide, and hydrazines to deliver aryl N-aminosulfonamides is described. The colorless crystalline solid DABCO·(SO(2))(2) was used as a convenient source of sulfur dioxide. The reaction tolerates significant variation of both the aryl iodide and hydrazine coupling partners.     

CO2 as Both a Selective Agent and Reaction Media in Palla-dium-Catalyzed Reductive Ullmann-Type Coupling Reaction

Carbon dioxide as both a selective agent and reaction media in the palladium-catalyzed Ullmann-type coupling has been described. The results showed that aryl chlorides could be easily activated in the presence of carbon dioxide and the chemoselectivity shifted toward the palladium-catalyzed Ullmann-type coupling reaction. In liquid carbon dioxide, homocoupling reactions of aryl halides, including less reactive aryl chlorides, were carried out smoothly in moderate to good yields using Pd/C, zinc, and H2O as the catalytic system at room temperature.