An efficient synthesis of biaryls via noncatalysed anionic coupling of an arylsodium with haloarenes

Noncatalysed anionic coupling of an arylsodium with haloarenes readily gives access to valuable biaryl structures. Compared to aryllithiums, the reaction with arylsodiums is faster and can be performed at lower temperature. The coupling with substituted haloarenes proceeds often with a high degree of regioselectivity. Since only cheap and readily available substrates are involved, this coupling is particularly suited for the large scale synthesis of basic biaryl building blocks.     

SnCl4-mediated oxidative biaryl coupling reaction of 1-naphthol and subsequent ring closure of 2,2′-binaphthol to the dinaphthofuran framework

A simple method for the direct synthesis of 2,2′-binaphthols 2 and dinaphtho[1,2-b;2′,1′-d]furans 3 under mild conditions was developed, utilizing a biaryl coupling reaction via electron donor-acceptor complexes of 1-naphthols with SnCl₄. Heating of the complex in a sealed tube for (18-24 h) afforded the corresponding o-o coupled product 2 in excellent yield. Prolonged reaction (56-65 h) under the same conditions afforded 3 in high yield in one step. We also found that in the case of α-naphthol without substituents other than a hydroxyl group at the C-1 position, regioselective o-o coupling reaction proceeded. The products 2a, 2b and 2g should be useful as synthetic intermediates for naturally occurring 3,3′-bijuglone, 3,3′-biplumbagin and elliptinone.     

Copper-catalyzed cascade coupling/cyclization of terminal alkynes with diazoacetates: a straightforward route for trisubstituted furans

A copper-catalyzed cascade coupling/cyclization of terminal alkynes with α-alkyl substituted diazoesters is developed. This new method furnished a straightforward route for 2,3,5-trisubstituted furan derivatives with good efficiency and selectivity.     

The Directed Synthesis of Biaryl Compounds: Modern Concepts and Strategies

The preparation and utilization of specific biaryl systems, particularly those which suffer hindered rotation, is a demanding goal not only in the synthesis of natural products and Pharmaceuticals, but also for example in the discovery of new reagents for asymmetric synthesis. This article will attempt to provide a topical review of modern, efficient processes for the specific preparation of biaryls. This appears to be of particular urgency, since, under the pressure of continually increasing demand, a wealth of new or modified synthetic approaches to the ever more important biaryl systems has been realized in recent years. The high standard which has been reached in this field is impressively demonstrated by regio- and stereoselective syntheses of important biaryl natural products such as steganone, ancistrocladine, ancistrocladisine, and dioncophylline A. Besides the utilization of asymmetric induction in the actual coupling step, the thermodynamically or kinetically controlled torsion of biaryl axes belongs to the most important concepts discussed.     

The remarkable configurational stability of ortho,ortho-tetrafluoro substituted biphenyls: 2,2,4,4,6,6-hexafluorobiphenyl-3,3-dicarboxylic acid as a model

Optically active 2,2^′,4,4^′,6,6^′-hexafluorobiphenyl-3,3^′-dicarboxylic acid was obtained through its brucine salt. The half-life time for racemization was determined at various temperatures and the torsional barrier for racemization was calculated to be 25.4 kcal/mol. These results prove, contrary to textbook knowledge, that ortho,ortho^′-tetrafluoro substituted biphenyls are resolvable.     

Direct ortho-arylation of 2-arylbenzoxazoles via C-H activation

A new and highly regioselective arylation of 2-arylbenzoxazoles based on C-H activation has been developed. The results represent the first examples of palladium-catalyzed direct ortho-arylation of 2-arylbenzoxazoles and also provide a facile route for the synthesis of complicated structures containing arylated benzoxazoles moieties.     

Synthesis of highly substituted quinolines via heterocyclization of fluorinated acetylenephosphonates with ortho-aminoaryl ketones

A synthetic route to a series of 4-alkyl- or arylquinolines, bearing in 2- and 3-position fluorinated and phosphonate functions at the same time, is reported for the first time. These compounds are synthesized via regioselective heterocyclization of XCF₂-alkynylphosphonates (X=F, Cl, Br, H, CF₃) with ortho-aminoaryl ketones (R=CH₃, CF₃, Ph) in the presence of K₂CO₃ or Li₂CO₃/TMEDA as mediators. 2-Fluoro- and 3-phosphorus-containing 4-Me, 4-CF₃ or 4-Ph quinolines are obtained in good to excellent yields. The influence of substituents in the aromatic ketone, the XCF₂-group in the alkyne as well as mediators and the reaction medium on the reactivity and specificity of the reaction is also investigated.     

Recyclable ligand-free mesoporous heterogeneous Pd catalysts for Heck coupling

Ligand-free Pd-MCM41 catalysts are highly active in the Heck coupling of bromoarenes including deactivated bromo derivatives to give coupled products in high yields with high selectivities without the need to exclude air or moisture. The catalyst samples exhibit unprecedented stability among heterogeneous catalysts and can be reused at least 20 times to achieve complete conversion without any additional activation treatment.     

Selective arylation of 1,1-disubstituted olefins using a biphenyl-based phosphine in Heck coupling reactions

The biphenyl-based phosphine, 2-diphenylphosphino-2′-methylbiphenyl is an effective ligand for palladium-catalyzed terminal arylation of 1,1-disubstituted olefins with aryl bromides in DMF and K₂CO₃ as base. The yields of products are independent of the electronic properties of the aryl bromides, however, the nature of the olefin has a major effect.     

Palladium complexes with ethylene-bridged bis(N-heterocyclic carbene) for C-C coupling reactions

A series of new ethylene-bridged bis(imidazolium) halides with various N-substitutions were synthesized. Complexation of these imidazolium halides with Pd(OAc)₂ produced new Pd(II) ethylene-bridged bis(carbene) complexes. Crystallographic analyses of some of the new imidazolium salts and Pd(II) complexes were determined. Applications of these seven-member palladacycles in Suzuki and Heck coupling reactions produced comparable catalytic activities to those of six-member analogs.     

Olefin-aminocarbyne coupling in diiron complexes: Synthesis of new bridging aminoallylidene complexes

The bridging aminocarbyne complexes [Fe₂{μ-CN(Me)(R)}(μ-CO)(CO)₂(Cp)₂][SO₃CF₃] (R = Me, 1a; Xyl, 1b; 4-C₆H₄OMe, 1c; Xyl = 2,6-Me₂C₆ H₃) react with acrylonitrile or methyl acrylate, in the presence of Me₃NO and NaH, to give the corresponding μ-allylidene complexes [Fe₂{μ-η¹:η³- C_α(N(Me)(R))C_β(H)C_γ(H)(R′)}(μ-CO)(CO)(Cp)₂] (R = Me, R′ = CN, 3a; R = Xyl, R′ = CN, 3b; R = 4-C₆H₄OMe, R′ = CN, 3c; R = Me, R′ = CO₂Me, 3d; R = 4-C₆H₄OMe, R′ = CO₂Me, 3e). Likewise, 1a reacts with styrene or diethyl maleate, under the same reaction conditions, affording the complexes [Fe₂{μ-η¹:η³-C_α(NMe₂)C_β(R′)C_γ(H)(R″)}(μ-CO)(CO)(Cp)₂] (R′ = H, R″ = C₆H₅, 3f; R′ = R″ = CO₂Et, 3g). The corresponding reactions of [Ru₂{μ-CN(Me)(CH₂Ph)}(μ-CO)(CO)₂(Cp)₂][SO₃CF₃] (1d) with acrylonitrile or methyl acrylate afford the complexes [Ru₂{μ-η¹:η³-C_α(N(Me)(CH₂Ph))C_β(H)C_γ(H)(R′)}(μ-CO)(CO)(Cp)₂] (R′ = CN, 3h; CO₂Me, 3i), respectively.The coupling reaction of olefin with the carbyne carbon is regio- and stereospecific, leading to the formation of only one isomer. C-C bond formation occurs selectively between the less substituted alkene carbon and the aminocarbyne, and the C_β-H, C_γ-H hydrogen atoms are mutually trans.The reactions with acrylonitrile, leading to 3a-c and 3h involve, as intermediate species, the nitrile complexes [M₂{μ-CN(Me)(R)}(μ-CO)(CO)(NC-CHCH₂)(Cp)₂][SO₃CF₃] (M = Fe, R = Me, 4a; M = Fe, R = Xyl, 4b; M = Fe, R = 4-C₆H₄OMe, 4c; M = Ru, R = CH₂C₆H₅, 4d).Compounds 3a, 3d and 3f undergo methylation (by CH₃SO₃CF₃) and protonation (by HSO₃CF₃) at the nitrogen atom, leading to the formation of the cationic complexes [Fe₂{μ-η¹:η³-C_α(N(Me)₃)C_β(H)C_γ(H)(R)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R = CN, 5a; R = CO₂Me, 5b; R = C₆H₅, 5c) and [Fe₂{μ-η¹:η³-C_α(N(H)(Me)₂)C_β(H)C_γ(H)(R)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R = CN, 6a; R = CO₂Me, 6b; R = C₆H₅, 6c), respectively.Complex 3a, adds the fragment [Fe(CO)₂(THF)(Cp)]⁺, through the nitrile functionality of the bridging ligand, leading to the formation of the complex [Fe₂{μ-η¹:η³-C_α(NMe₂)C_β(H)C_γ(H)(CNFe(CO)₂Cp)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (9).In an analogous reaction, 3a and [Fe₂{μ-CN(Me)(R)}(μ-CO)(CO)₂(Cp)₂][SO₃CF₃], in the presence of Me₃NO, are assembled to give the tetrameric species [Fe₂{μ-η¹:η³-C_α(NMe₂)C_β(H)C_γ(H)(CN[Fe₂{μ- CN(Me)(R)}(μ-CO)(CO)(Cp)₂])}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R = Me, 10a; R = Xyl, 10b; R = 4-C₆H₄OMe, 10c).The molecular structures of 3a and 3b have been determined by X-ray diffraction studies.     

Regioselective ortho-nitration of N-phenyl carboxamides and primary anilines using bismuth nitrate/acetic anhydride

An efficient and one-pot synthetic method for the regioselective ortho-nitration of the N-phenyl carboxamides and primary anilines has been developed by using bismuth nitrate and acetic anhydride as the nitrating reagents. Reaction proceeds at room temperature and results in corresponding ortho-nitrated products in moderate to excellent yields. This method provides an operationally simple, regioselective, and efficient access to synthesize o-nitro anilines under the mild conditions.     

Microwave-assisted synthesis of 4H-benzo[f]imidazo[1,4]diazepin-6-ones via a post-Ugi copper-catalyzed intramolecular Ullmann coupling

An efficient post-Ugi copper-catalyzed intramolecular Ullmann coupling strategy has been elaborated for the diversity-oriented synthesis of 4H-benzo[f]imidazo[1,4]diazepin-6-ones and the scope and limitations of this protocol are investigated.     

Microwave-assisted Stille and Hiyama cross-coupling reactions catalyzed by ortho-palladated complexes of homoveratrylamine

The activity of dimeric [Pd{C₆H₂(CH₂CH₂NH₂)-(OMe)₂-3,4}(μ-Br)]₂ and monomeric [Pd{C₆H₂(CH₂CH₂NH₂)-(OMe)₂-3,4}Br(PPh₃)] complexes as efficient, air, and moisture tolerant catalysts was investigated in Stille and Hiyama cross-coupling reactions of various aryl halides. Substituted biaryls were produced in excellent yields in short reaction times using these complexes. The monomeric complex had been demonstrated to be more active than the corresponding dimeric catalyst for the cross-coupling of some of aryl bromides and unreactive aryl chlorides. The combination of homogenous metal catalyst, microwave irradiation, and microwave-active polar solvents gave high yields of products in short reaction times.     

The metal-halogen exchange reaction between ortho-substituted aryl halides and Ph2CuLi · LiCN: scope and applicability for coupling reactions

Metal-halogen exchange between Ph₂CuLi · LiCN and ortho-substituted aryl iodides or bromides may be used to conveniently afford substituted metallated aryls which can subsequently undergo reaction with electrophiles.     

A new approach for the ortho-substitution of anilines and for the synthesis of indolines

Intermolecular radical addition of a xanthate to a vinyl sulfanilide is followed by ring closure to the aromatic ring to give a dihydrobenzoisothiazole dioxide structure, which upon heating loses sulfur dioxide to give a 2-substituted aniline; in some examples, the presence of DBU during heating induces the formation of an indoline.     

One-pot synthesis of recyclable palladium catalysts for hydrogenations and carbon-carbon coupling reactions

Palladium nanoparticles were generated from tetrakis(triphenylphophine)palladium in a mixture of tetra(ethylene glycol) and tetramethoxysilane (or titanium(IV) isopropoxide), then encapsulated in silica matrix (or titania matrix) by the treatment with water. The resulting heterogeneous material showed high catalytic activity in the hydrogenations of various alkene and alkynes and in the carbon-carbon cross-coupling reactions such as the Suzuki-Miyaura, the Sonogashira, the Heck-Mizoroki, and the Stille reactions.     

One-pot synthesis of ortho-hydroxycinnamate esters

Phenols are converted to salicylaldehydes with paraformaldehyde, MgCl₂-Et₃N in THF, and subsequent treatment with methyl (triphenylphosphoranylidene)acetate gave the corresponding methyl ortho-hydroxycinnamate derivatives. The sequence is conveniently carried out as a one-pot procedure.     

An iterative acetylene-epoxide coupling strategy for the total synthesis of longimicin C

Longimicin C, a naturally occurring annonaceous acetogenin possessing a C₂-symmetrical bis-THF moiety and a short hydrocarbon chain between its THF-containing region and a terminal γ-lactone, was synthesized for the first time. The total synthesis was successfully achieved by an iterative acetylene-epoxide coupling strategy. d-Mannitol was used to establish the bis-THF-containing segment, in which the additional stereochemistries were introduced by Sharpless dihydroxylations and intramolecular Williamson etherifications. Regioselective epoxide-openings by the appropriate terminal acetylenes allowed coupling and elaboration of all four fragments including the introduction of three essential hydroxyls into the proper sites of the target skeleton.