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Density functional theory computation indicates that bridge splitting of [PtII R2 (μ-SEt2 )]2 proceeds by partial dissociation to form R2 Pta (μ-SEt2 )Ptb R2 (SEt2 ), followed by coordination of N-donor bromoarenes (L-Br) at Pta leading to release of Ptb R2 (SEt2 ), which reacts with a second molecule of L-Br, providing two molecules of PtR2 (SEt2 )(L-Br-N). For R=4-tolyl (Tol), L-Br=2,6-(pzCH2 )2 C6 H3 Br (pz=pyrazol-1-yl) and 2,6-(Me2 NCH2 )2 C6 H3 Br, subsequent oxidative addition assisted by intramolecular N-donor coordination via PtII Tol2 (L-N,Br) and reductive elimination from PtIV intermediates gives mer-PtII (L-N,C,N)Br and Tol2 . The strong σ-donor influence of Tol groups results in subtle differences in oxidative addition mechanisms when compared with related aryl halide oxidative addition to palladium(II) centres. For R=Me and L-Br=2,6-(pzCH2 )2 C6 H3 Br, a stable PtIV product, fac-PtIV Me2 {2,6-(pzCH2 )2 C6 H3 -N,C,N)Br is predicted, as reported experimentally, acting as a model for undetected and unstable PtIV Tol2 {L-N,C,N}Br undergoing facile Tol2 reductive elimination. The mechanisms reported herein enable the synthesis of PtII pincer reagents with applications in materials and bio-organometallic chemistry.

Bipyridine- and benzimidazole-based ligands for the self-assembly of Co4L6 cages were synthesised in short reaction times and high isolated yields directly from aryl halide precursors using a copper-free one-pot Sonogashira-type coupling. This one-pot method circumvents the often time-consuming and challenging ligand synthesis for the preparation and application of cages.

A palladium-catalyzed cross-coupling reaction with aryl halide functionalities has recently emerged as a valuable tool for protein modification. Herein, a new fluorogenic modification methodology for proteins, with genetically encoded fluorosulfate-l-tyrosine, which exhibits high efficiency and biocompatibility in bacterial cells as well as in aqueous medium, is described. Furthermore, the cross-coupling of 4-cyanophenylboronic acid on green fluorescent protein was shown to possess a unique fluorogenic property, which could open up the possibility of a responsive "off/on" switch with great potential to enable spectroscopic imaging of proteins with minimal background noise. Taken together, a convenient and efficient catalytic system has been developed that may provide broad utilities in protein visualization and live-cell imaging.

Palladium-catalyzed alkene-directed cross-coupling of aryl iodide with another aryl halide through C-H arylation opens a unique avenue for unsymmetrical biaryl-derived molecules. However, homo-coupling of aryl iodides often erodes the overall synthetic efficiency. Reported herein is a highly chemoselective Pd0 -catalyzed alkyne-directed cross-coupling of aryl iodides with bromophenols, which was subsequently followed by phenol dearomatization to furnish a very attractive [2+2+1] spiroannulation. Notably, possible homo-coupling of aryl iodides was not observed at all. Mechanistic studies indicated that a five-membered aryl/vinyl palladacycle most likely accounts for promoting the key step of biaryl cross-coupling.

A highly regioselective Ni-catalyzed electrochemical reductive relay cross-coupling between an aryl halide and an alkyl halide has been developed in an undivided cell. Various functional groups are tolerated under these mild reaction conditions, which provides an alternative approach for the synthesis of 1,1-diarylalkanes.

A rare reductive coupling of nitro compounds with organohalides has been realized. The reaction is initiated by a partial reduction of the nitro group to a nitrenoid intermediate. Therefore, not only aromatic but also aliphatic nitro compounds are efficiently transformed into monoalkylated amines, with organohalides as the alkylating agent. Given the innate reactivity of the nitrenoid, a catalyst is not required, resulting in a high tolerance for aryl halide substituents in both starting materials.

A Pd0 -catalyzed four-component cascade reaction of an aryl halide, CO, an N-tosylhydrazone, and an amine affording α-amino ketone has been developed. This reaction involves a sequential carbonylation, metal carbene migratory insertion, and amination. Control experiments and DFT calculations further reveal the reaction sequence and chemoselectivity of individual components in this cascade process.

Manipulating particle size is a powerful mean of creating unprecedented applications both in inorganic and organic materials. Coordination polymer, emerging as one sort of organic-inorganic hybrid materials, has attracted thriving interests in a variety of applications, but nanoscale coordination polymer has scarcely been touched. In this work, pure-phase coordination polymer [Cu6(1,4-bis(imidazol-1-yl)butane)3I6]∞ with different sizes as well as morphologies was synthesized through facile top-down route assisted with solvent-etching for the first time. The size and morphology could be adjusted just via varying the participated etching solvents. Our mechanistic investigation suggest that the bulk coordination polymer as precursor in the etching solvents may experience a process of dispersion, dissolvation, recrystalization to generate the nanoscale counterpart. Higher catalytic activity of nanoscale coordination polymer was observed in N-arylation of imidazole aryl halide, and was attributed to higher surface area and lower coordination number of unsaturated coordination sites (CUSs). This simple and rapid preparation, requiring neither specialized equipment nor harsh conditions, suggests a wealth of potential for reducing down the size of coordination polymer to comply with various practical applications.

A highly efficient method for the preparation of 4-alkoxy-3-bromophenyl boronic acid N-methyliminodiacetic acid (MIDA) esters as building blocks in iterative Suzuki-Miyaura reactions from the 4-alkoxyphenylboronic acids is described using a boronic acid moiety as a blocking group in bromination reactions. With these MIDA boronates, the total syntheses of dictyoterphenyls A and B were developed in only two separate one-pot operations. Furthermore, we have developed a more practical protocol for the preparation of meta-terphenyl natural products by simply adding the second aryl halide and water to the reaction mixture via the controlled release technique.

The substrate scope and the mechanism have been investigated for the MnCl2-catalyzed cross coupling reaction between aryl halides and Grignard reagents. The transformation proceeds rapidly and in good yield when the aryl halide is a chloride containing a cyano or an ester group in the para position or a cyano group in the ortho position. A range of other substituents gave no conversion of the aryl halide or led to the formation of side products. A broader scope was observed for the Grignard reagents where a variety of alkyl- and arylmagnesium chlorides participated in the coupling. Two radical clock experiments were performed which in both cases succeeded in trapping an intermediate aryl radical. The cross coupling is therefore believed to proceed by a SRN1 mechanism, where a triorganomanganate complex serves as the most likely nucleophile and single electron donor. Other mechanistic scenarios were excluded based on the substrate scope of the aryl halide.

An efficient and facile route has been developed by using greener and reusable deep eutectic solvent (DES) for the synthesis of O-arylated ethers. This process involves nucleophilic aromatic substitution (SNAr) of various strongly electron-deficient aryl/alkyl halides and phenols with different substituents resulting in good to excellent yields of products (80-96 %). A significant enhancement in the yield as well as rate of the reaction is observed with increase in presence of electron-withdrawing functionality attached to aryl halide moiety. Simplicity of this catalytic system, cheap cost and easy product isolation procedure makes this protocol economically viable and comparable to metal/ligand catalysed reactions utilizing aprotic solvents. Moreover, the other significant advantages of this method includes mild reaction conditions, short reaction times, easy work up procedure and recyclability of the catalyst up to four runs without remarkable loss in activity.

The aryl methyl group is found in many drug-like compounds, but there are limited ways of preparing compounds with an isotope label in this methyl position. The process of cyanation of an aryl halide followed by complete reduction of the nitrile to a methyl group was investigated as a route for preparing stable and radiolabelled isotopologues of drug-like compounds. Using this methodology, carbon-13, deuterium, carbon-14, and tritium labelled isotopologues of the nonsteroidal anti-inflammatory drug tolmetin were produced, as well as carbon-13, deuterium, and carbon-14 labelled isotopologues of another nonsteroidal anti-inflammatory drug, celecoxib. The radiolabelled compounds were produced at high specific activity and the stable isotope labelled compounds with high incorporation making them suitable for use as internal standards in mass spectrometry assays. This approach provides a common synthetic route to multiple isotopologues of compounds using inexpensive and readily available labelled starting materials.

A novel protocol is reported for the facile one-pot benzimidazole derivatives formation from Pd-catalyzed reaction of aryl halides (X=I, Br, -Cl), Fe(CO)5, and o-diaminobenzene or o-nitroaniline. Aryl halides are first converted to aryl aldehydes using Fe(CO)5 which then undergo ring closure with o-diaminobenzene or o-nitroaniline in DMF at 110 °C under Ar. In the case of o-nitroaniline, the reduction of the nitro group takes place before the cyclization step in the presence of reducing agents such as Fe(CO)5, released CO, Pd(0) and also P(III) in the reaction mixture. There is no need for employing P(III) ligand in case of aryl iodides while P(III) ligand is necessary for aryl bromides and chlorides to facilitate the reaction. In this reaction, Fe(CO)5 is not only responsible as the CO source and reduction of -NO2 functionality in o-nitroaniline, but also produces iron oxides residue in the reaction which are responsible for the dehydrogenation step.

This contribution describes the reactivity of a zero-valent palladium phosphine complex with substrates that contain both an aryl halide moiety and an unsaturated carbon-carbon bond. Although η(2) -coordination of the metal center to a C=C or C≡C unit is kinetically favored, aryl halide bond activation is favored thermodynamically. These quantitative transformations proceed under mild reaction conditions in solution or in the solid state. Kinetic measurements indicate that formation of η(2) -coordination complexes are not nonproductive side-equilibria, but observable (and in several cases even isolated) intermediates en route to aryl halide bond cleavage. At the same time, DFT calculations show that the reaction with palladium may proceed through a dissociation-oxidative addition mechanism rather than through a haptotropic intramolecular process (i.e., ring walking). Furthermore, the transition state involves coordination of a third phosphine to the palladium center, which is lost during the oxidative addition as the C-halide bond is being broken. Interestingly, selective activation of aryl halides has been demonstrated by adding reactive aryl halides to the η(2) -coordination complexes. The product distribution can be controlled by the concentration of the reactants and/or the presence of excess phosphine.

Two coumarins isolated from Aster praealtus were synthesized via a direct coupling of the corresponding cyclohexyl carbinol with a coumarin-derived aryl bromide or iodide, a very difficult etherification due to the excess steric congestion around the carbinol and the low reactivity of the aryl halide that frustrated many seemingly feasible protocols. Unequivocal 1H and 13C NMR data for these compounds were thus made available for the first time. Uncertainty and errors in 1H and 13C NMR data in previous reports are also eliminated and revealed, respectively.

Novel triarylamine-based coordination-saturated aryl Pd(II) halide complexes ligated by PEt3, PCy3, and P(o-tol)(3) were successfully synthesized by direct oxidative addition of aryl halide to the corresponding Pd(0) precursors. Suzuki-Miyaura coupling polymerization of 2-(7-halide-9,9-dioctylfluoren-2-yl)-1,3,2-dioxaborinane with these Pd(II) complexes as initiators was investigated for the synthesis of poly(fluorene)s with triarylamine end group. Pd(II) complexes with PCy3 or P(o-tol)(3) exhibited catalytic activity and realized the catalyst-transfer polycondensation at 75 degrees C and room temperature, respectively, while the polymerization using Pd(II) catalyst ligated by PEt3 did not proceed, which indicated that the bulky phosphine ligands could facilitate the reductive elimination and further promote the polymerization. In addition, the dimeric Pd(II) complex with P(o-tol)(3) can convert into monomeric Pd(II) intermediate with an open coordination site, which had a higher activity. The end groups of the afforded polyfluorene were analyzed by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, in which the Ar/H end groups are indicative of the catalyst-transfer polymerization. (c) 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1457-1463

An efficient one-step synthetic strategy was used to prepare a set of dicarboxamides through palladium-catalysed amino carbonylation of iodoalkenyl and iodoaryl compounds, with use of various alkyl- and aryldiamines as N-nucleophiles. The isolated yields of the dicarboxamides depended signifi cantly on the iodo substrate and diamine structures, as well as on the reaction conditions, the best one (ca. 70 %) being achieved with 1-iodocyclohexene as substrate and 1,4-di aminobutane as nucleophile, at 100 °C and 30 bar of CO. When iodobenzene was used as model aryl halide, the high est yield of the target dibenzamides (ca. 65 %) was obtained with 1,4-diaminobenzene as coupling amine, at 100 °C and 10 bar of CO. Preliminary studies on their in vitro cytotoxicity against human lung carcinoma A549 cells showed N,N�- (butane-1,4-diyl)dibenzamide and androst-16-ene-based di carboxamides to be the most efficient cytotoxic agents, with IC50values of approximately 40μM.

A new strategy is reported that allows direct access to 11C-labelled aryl methyl ketones by a fast and efficient (carbonyl)cobalt-mediated protocol employing [11C]methyl iodide as the labelling agent. The method uses Co2CO8 as combined aryl halide activator and carbon monoxide source for the carbonylation reaction. The suitability of the methodology was demonstrated by the 11C-labelling of a set of functionalised arenes and heteroarenes with radiochemical conversions (RCC) ranging from 22 % to 63 %.

β-Hydride abstraction is a well-accepted elementary step for catalytic cycles in organometallic chemistry. It is usually anticipated that alkylpalladium halides containing syn-β-hydrogen atoms will undergo β-hydride abstraction to afford the Heck-type products. However, this study discloses that the above general knowledge is only conditionally correct. Our experimental results demonstrate that the reductive elimination of alkylhalides from alkylpalladium halides containing syn-β-hydrogen atoms may surpass the β-hydride abstraction or even become exclusive in certain cases.

Photolysis of [Cp*Re(CO)3] (Cp* = η5-C5Me5) with bromobenzene or chlorobenzene in benzene results in biphenyl and the corresponding rhenium hydride halide complex trans-[Cp*Re(CO)2H(X)], which further converts into the dihalide complexes cis/trans-[Cp*Re(CO)2X2] (X = Br, Cl). Additional experiments, including isotopic labeling experiments, indicate that one phenyl ring in biphenyl comes from the aryl halide and the other one comes from solvent benzene. Photolysis of [CpRe(CO)3] (Cp = η5-C5H5) with aryl halide in benzene similarly generates biphenyl, the corresponding rhenium hydride halide complex. Furthermore, the reaction also affords small amounts of rhenium dihydride complex [CpRe(CO)2H2]. Plausible mechanisms for the formation of the different types of products are proposed that involve intermolecular C–X and C–H activation. Molecular structures of trans-[Cp*Re(CO)2(Br)(Cl)] (trans-6) and trans-[CpRe(CO)2(Br)(Cl)] (trans-12) determined by X-ray diffraction are also presented.

An efficient palladium catalyst was synthesized using nicotine, benzyl chloride and palladium chloride. The structure of this catalyst was characterized and it was then used for the synthesis of diaryl sufides. A variety of diaryl thioethers were synthesized under relatively mild reaction conditions. This protocol avoids foul-smelling thiols via cross-coupling of aryl halides with potassium thiocyanate and all substrates give the corresponding products in good to excellent yields in the presence of low amounts of the catalyst. Copyright © 2014 John Wiley & Sons, Ltd.

This work reports Suzuki–Miyaura cross-coupling reactions of arylboronic acid with aryl halide or aryl dibromide mediated by PdCl2 (0.05 mol%) and sodium 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-1-yl)butane-1-sulfonate (0.05 mol%) at 100 °C in water. The corresponding cross-coupling products were obtained in good to excellent yields. The catalytic system was recovered from the organic products by extraction with ether and the residual aqueous catalyst phase showed high activity after reuse of at least four cycles. Copyright © 2014 John Wiley & Sons, Ltd.

Homocoupling of aryl halides (2 ArX → Ar―Ar) promoted by NiCl2/2,2′-bipyridine (bpy)/Mg mixtures in DMF has been studied. Mixtures of NiCl2, bpy and Mg in DMF promoted homocoupling of aryl halides such as phenyl bromide and p-tolyl bromide to give the coupling products in good (e.g. approximately 60–75%) yields, and the homocoupling products were easily isolated from the reaction mixtures. Application of this homocoupling to dibromo-aromatic compounds (Br–arylene–Br: 2,5-dibromopyridine, 2,7-dibromo-9.9-dioctylfluorene and 2,7-dibromo-9,10-dioctyl-9,10-dihydrophenanthrene) gave the corresponding π-conjugated polymers, –(arylene)n–, in good yields. Organometallic processes for the homocoupling are discussed. Copyright © 2014 John Wiley & Sons, Ltd.

Potassium acyltrifluoroborates (KATs) are fascinating functional groups whose further exploration is limited by poor synthetic access. Documented herein is the design and synthesis of a new reagent for their one-step preparation from aryl- and heteroarylhalides. The reagent is a stable, soluble zwitterion prepared by S-alkylation of a novel thioformamide trifluoroboronate. The KATs are prepared by adding one equivalent of nBuLi to a mixture of the aryl halide and the reagent at -78 °C. This protocol is suitable for the preparation of KATs containing pyridines, esters, nitro groups, and halides.

Two new [Ni(allyl)Cl(NHC)] complexes with the bulky yet flexible N-heterocyclic carbene (NHC) ligands IPr* {N,N'-bis[2,6-bis(diphenylmethyl)-4-methylphenyl]imidazole-2-ylidene} and IPr*OMe {N,N'-bis[2,6-bis(diphenylmethyl)-4-methoxyphenyl]imidazol-2-ylidene} are reported. These complexes were employed in the amination and sulfination of aryl halide species and were shown to perform well in these reactions, which typically required less than half as much catalyst as previous state-of-the-art nickel complexes.

A palladium catalyzed CH activation/ortho-arylation of heteroaryl-N-oxides through a decarboxylative coupling of heteroaryl carboxylic acids is described. Heterobiaryl-N-oxides, which are difficult to access by conventional methods, can be obtained in a single step. A wide range of functional groups, including metal-susceptible groups, such as bromo and iodo, can be tolerated under the reaction condition. The regioselectivity with respect to both carboxylic acid and N-oxide is excellent. Further, the N-oxides were used as a tool to examine the efficiency of decarboxylative coupling compared with aryl halide coupling.

Direct cross-coupling between an arylzinc reagent and an aryl halide was accomplished without any external catalyst, enabling efficient and selective formation of the corresponding biaryl compound with broad functional group compatibility.

Transition-metal-catalyzed aromatic C–H oxygenation reaction[1] is a very powerful tool for straightforward synthesis of valuable oxygen-containing products from abundant arenes.[2] Of these reactions, intramolecular C–H/O–H oxidative coupling of carboxylic acid with unactivated sp2 C–H bond is an important transformation, because it gives an access to a variety of valuable lactone-containing molecules.[3] Thus, 3,4-benzocoumarin fragment 2, containing six-membered lactone moiety, is widely found in natural and bioactive molecules, as well as in useful materials.[4] Expectedly, 2 can be accessed through cyclization of nonpre-functionalized 2-arylbenzoic acids 1; however, the existing methods require either employment of stoichiometric amounts of toxic oxidants[5] or UV irradiation,[6] which substantially limits applicability of these methods (Scheme 1). We hypothesized that it should be possible to develop a general, practical, and environmentally benign dehydrogenative C–H/O–H lactonization reaction of 2-arylbenzoic acids 1 into 3,4-benzocoumarins 2 en route to oxygenated biaryls 3. We envisioned that C–H oxygenation could potentially be performed by formation of carboxyl O-centered radical A, which would undergo a subsequent C–O bond formation.[7] Scheme 1 Carboxyl-group-directed C–H oxygenation reactions. Herein, we report two complimentary methods for this transformation. Method 1, the Cu-catalyzed oxygenation reaction of 2-arylbenzoic acids, which is efficient for electron-neutral and electron-rich substrates. During preparation of this manuscript, a similar to Method 1 Cu-catalyzed transformation was disclosed by Gallardo-Donaire and Martin.[8] Most importantly, we also developed a more general and practical Method 2, the K2S2O8-mediated oxygenation reaction, which is widely applicable for cyclization of electron-neutral, electron-rich, as well as electron-deficient substrates. To develop mild and environmentally benign intramolecular lactonization reaction of 2-arylbenzoic acids, we performed extensive screening of transition-metal catalysts and oxidants.[9] It was found that this reaction can efficiently be accomplished by using CuII catalyst. Thus, 2-phenylbenzoic acid 1a was converted into the desired benzocoumarin product 2a in 88% yield in the presence of Cu(OAc)2·H2O (5 mol%) and tert-butyl peroxybenzoate (TBPB, Luperox P) in dichloroethane (Method 1). We found that substrates with electron-neutral and electron-donating substituents, as well as aryl halide fragments (Hal=F, Cl, Br) and cyanogroup on the “guest” aryl ring, produced the desired products in good to excellent yield (Table 1, entries 2a–j). In general, benzoic acids substituted with arene ring containing meta-substituents (F, Cl, OMe, tBu) preferentially underwent cyclization at the less hindered site (Table 1, entries 2k–n). In contrast, meta-Me substituted substrate 1o cyclized at the more hindered site producing 2o as a major regioisomer (4:1).[10] In addition, 2-naphthyl substituted benzoic acid 1p gave the product of cyclization at the more electron-rich 1-position, exclusively (2p). Likewise, substrates containing 3,5-disubstituted arene ring also underwent efficient cyclization into benzocoumarin products 2q and r. 2-Phenylbenzoic acids containing substituents at 1-, 2-, and 3-positions also underwent smooth C–H oxygenation reaction producing products 2s–v. Although electron-neutral and electron-rich substrates under these reaction conditions (Method 1) gave the corresponding benzocoumarins in good to excellent yields, cyclization reaction of electron-deficient substrates was less efficient. Hence, 2-arylbenzoic acids with important electron-withdrawing functional groups, such as CF3 (1w), COMe (1x), and CONMe2 (1y) provided the corresponding products in diminished yields, whereas substrates possessing CHO (1z), CF3 (1aa, ab), and NO2 groups (1ac–ae) produced trace to no product at all (Table 1). Table 1 CuII-catalyzed C–H oxygenation reaction. To overcome this limitation of the Cu-catalyzed oxygenation reaction (Method 1, Table 1), we aimed at the development of a complementary method for cyclization of electron deficient 2-arylbenzoic acids. Delightfully, we found that this transformation can be performed in the presence of K2S2O8 oxidant in aqueous acetonitrile.[11] Thus, benzocoumarin 2a was formed in 93% yield from 2-phenylbenzoic acid 1a in gram-scale manner by using this convenient and environmentally benign protocol (Table 2). We found that Method 2 works efficiently for electron-neutral and electron-deficient substrates under these conditions (entries 2a, i,p, r, t,u). Notably, in the presence of K2S2O8, benzoic acids substituted with arene ring containing meta-substituents produced the corresponding products in higher selectivity compared to that of Method 1 (Table 2, entries 2k–o′). Most importantly, the developed protocol can be successfully applied to a variety of electron-deficient substrates. Accordingly, 2-arylbenzoic acids with CF3 (2w, 2aa), COMe (2x), CONMe2 (2y), and CHO (2z) groups underwent cyclization producing the corresponding products in good to excellent yields. Moreover, previously incompetent substrates with highly electron- withdrawing NO2 group (2ac, 2ad, 2ae) and even two CF3 groups (2ab) now were smoothly transformed into the corresponding benzocoumarin products (Method 1, Table 1). It should be mentioned that in some cases, addition of a catalytic amount of AgNO3 (10 mol%) led to substantial increases of reaction rates.[12, 13] Table 2 K2S2O8-mediated C–H oxygenation reaction. Naturally, the developed methods open access to a variety of densely functionalized benzocoumarin molecules.[4] In addition, considering the importance of aryl ether moiety, we have shown that the obtained 3,4-benzocoumarins could be nearly quantitatively converted into the corresponding biaryl ethers 3 (Scheme 2). Scheme 2 Conversion of lactones into aryl ethers. It is likely that the CuII-catalyzed oxygenation reaction (Method 1) proceeds through an active CuIII intermediate A (Scheme 3), which may abstract the adjacent hydrogen atom to form aryl radical B (Path A). The latter, upon oxidative ring closure, would produce B′, followed by a reductive elimination to form 2.[14, 15] Alternatively, a single-electron transfer (SET) process in A would give radical–cation specie C (Path B), which would be transformed into 2 by a subsequent C–O bond-forming reaction.[16] Scheme 3 Proposed mechanism for Method 1. The K2S2O8-mediated oxygenation reaction (Method 2) most likely proceeds by oxidation of benzoic acid 1 into an O-centered carboxylic radical D, which undergoes addition to the arene ring to form an aryl radical intermediate E (Scheme 4, [Eq. (1)], Path A). The latter converts into the benzocoumarin product 2a upon loss of a hydrogen radical. This homolytic aromatic substitution mechanism is supported by our experiments on cyclization of substrates containing 2-haloaryl substituents 4a–c (G= F, Cl, Br). It was found that these reactions exclusively produce substitution products 2a instead of possible C–H coupling products 5 (Scheme 4, [Eq. (2)]).[17] Alternative mechanism involving an abstraction of hydrogen radical from the aromatic ring in the intermediate D to form the aromatic radical F cannot be ruled out at this stage (Scheme 4, [Eq. (1)], Path B). Scheme 4 Proposed mechanism for Method 2. In conclusion, two complimentary methods for carboxyl-group- directed remote C–H oxygenation reaction of arenes were developed. Method 1, the Cu-catalyzed reaction, produces a variety of 3,4-benzocoumarins containing electron-neutral and electron-releasing substituents. In addition, a more general Method 2, the K2S2O8-mediated transformation, which is widely applicable to various electron-rich and electron-deficient 2-arylbenzoic acids, was developed. This protocol features a broad scope, a good functional group tolerance, and good selectivity. It is also benign, operationally simple, easily scalable, and proceeds under mild conditions.

Oxidative addition (OA) of an aryl halide to palladium(0) is the first step in the catalytic cycle of many palladium-catalyzed cross-coupling reactions that have found wide use in industrial and pharmaceutical applications. A great deal of effort has gone into understanding the mechanistic details of the OA process, and much progress has been made. For example, it is well established that the propensity of aryl halides towards oxidative addition increases in the order ArF

A novel palladium-catalyzed coupling reaction of an aryl methyl ketone with two molecules of an aryl halide to yield symmetric diarylmethanes is described. In the facile one-pot reaction, the aryl methyl ketone acts as a formal methylene donor. The experimental facts, including TLC monitoring, speculated intermediates as the raw materials, analysis of the cesium benzoate coproduct by ex situ IR spectroscopy, and the cross-coupling reactions of two different aryl halides, indicate a mechanism involving a palladium-catalyzed sequential two-step coupling process, in which the presence of a trace amount of H2O is indispensable. The reaction is applicable to a broad spectrum of substrates and delivers the products in good to excellent yields. Access to unsymmetrical diarylmethanes with this method is also explored and various factors are discussed.

Polyethylene glycols (PEGs) with different molecular weights (Mw = 200, 400, 1000) were phosphorylated to their bis-diphenyl phosphinite derivatives as stable solids which are melted in the range 140–160°C. These phosphorylated PEGs were used as ligands and reducing agents to generate nano-Pd(0) catalysts in 2.5–8.3 nm. The nano-Pd(0) particles supported on phosphorylated PEG200 were applied for the efficient Heck–Mizoroki carbon–carbon coupling reactions of ArX (X = Cl, Br, I) at 80–100°C under solvent-free conditions and for the Suzuki–Miyaura coupling reaction in ethanol at 70°C. The catalyst was recycled easily and reused for several runs. Copyright © 2013 John Wiley & Sons, Ltd.

The synthesis of 3-aryl-3-hydroxy-2-oxindoles, which are a structural motif found in various natural products and pharmaceutically active compounds, was conducted via reductive coupling of (2-aminophenyl)(aryl)methanone derivatives and CO2 as a key step. The conditions employing Mg with chlorotrimethylsilane in DMA are the best for the reductive coupling, where the aryl halide moiety is intact. This reaction proceeds well without the protection of the amino group. The reductive coupling and acid-catalyzed lactam formation can be performed in a one-pot reaction to give the oxindoles.

Substrates bearing both a β-ketoester moiety and a (het)aryl halide structure element were dimerized to 1-naphthols and related products in the presence of catalytic amounts of CuI in isopropanol. The reaction starts with an intermolecular C-arylation, which is followed by an intramolecular condensation. The final aromatization delivers the highly substituted products with yields up to 81%.

A rapid, chemoselective and metal-free C–B bond-forming reaction of aryl iodides and bromides in aqueous solution at low temperatures was discovered. This reaction is amenable to batch and continuous-flow conditions and shows exceptional functional group tolerance and broad substrate scope regarding both the aryl halide and the borylating reagent. Initial mechanistic experiments indicated a photolytically generated aryl radical as the key intermediate.

The reduction and reductive addition (formal hydroamination) of functionalised nitroarenes is reported using a simple and bench-stable iron(III) catalyst and silane. The reduction is chemoselective for nitro groups over an array of reactive functionalities (ketone, ester, amide, nitrile, sulfonyl and aryl halide). The high activity of this earth-abundant metal catalyst also facilitates a follow-on reaction in the reductive addition of nitroarenes to alkenes, giving efficient formal hydroamination of olefins under mild conditions. Both reactions offer significant improvements in catalytic activity and chemoselectivity and the utility of these catalysts in facilitating two challenging reactions supports an important mechanistic overlap.

An efficient strategy has been developed for the N-arylation of azoles and aliphatic amines with aryl halide using a Cu2O/nano-CuFe2O4 magnetic composite as the catalyst and KOH as the base. The me...

A palladium-catalyzed direct synthesis of symmetric biaryl compounds from aryl halides in the presence of tBuLi is described. In situ lithium-halogen exchange generates the corresponding aryl lithium reagent, which undergoes a homocoupling reaction with a second molecule of the aryl halide in the presence of the palladium catalyst (1 mol %). The reaction takes place at room temperature, is fast (1 h), and affords the corresponding biaryl compounds in good to excellent yields. The application of the method is demonstrated in an efficient asymmetric total synthesis of mastigophorene A. The chiral biaryl axis is constructed with an atropselectivity of 9:1 owing to catalyst-induced remote point-to-axial chirality transfer.

The palladium-catalyzed coupling of an enolate with an ortho-functionalized aryl halide (an α-arylation) furnishes a protected 1,5-dicarbonyl moiety that can be cyclized to an isoquinoline with a source of ammonia. This fully regioselective synthetic route tolerates a wide range of substituents, including those that give rise to the traditionally difficult to access electron-deficient isoquinoline skeletons. These two synthetic operations can be combined to give a three-component, one-pot isoquinoline synthesis. Alternatively, cyclization of the intermediates with hydroxylamine hydrochloride engenders direct access to isoquinoline N-oxides; and cyclization with methylamine, gives isoquinolinium salts. Significant diversity is available in the substituents at the C4 position in four-component, one-pot couplings, by either trapping the in situ intermediate after α-arylation with carbon or heteroatom-based electrophiles, or by performing an α,α-heterodiarylation to install aryl groups at this position. The α-arylation of nitrile and ester enolates gives access to 3-amino and 3-hydroxyisoquinolines and the α-arylation of tert-butyl cyanoacetate followed by electrophile trapping, decarboxylation and cyclization, C4-functionalized 3-aminoisoquinolines. An oxime directing group can be used to direct a C-H functionalization/bromination, which allows monofunctionalized rather than difunctionalized aryl precursors to be brought through this synthetic route.