Neutral Aryl Research Articles

Binaphthyl-Based Chiral Macrocyclic Hosts for the Selective Recognition of Iodide Anions.

In this study, we explorethe synthesis of binaphthyl-based chiral macrocyclic hosts for the first time. They exhibited the selective recognition abilities of iodide anions which can be favored over those of other anions (AcO-, NO3-, ClO4-, HSO4-, Br-, PF6-, H2PO4-, BF4-, and CO3F3S-), as confirmed by UV-vis, HRMS, and 1H NMR spectroscopy experiments, as well as DFT calculations. Neutral aryl C-H···anion interactions play an important role in the formation complexes. The recognition process can be observed by the naked eye.

Catalytic SNAr Hydroxylation and Alkoxylation of Aryl Fluorides

AbstractNucleophilic aromatic substitution (SNAr) is a powerful strategy for incorporating a heteroatom into an aromatic ring by displacement of a leaving group with a nucleophile, but this method is limited to electron‐deficient arenes. We have now established a reliable method for accessing phenols and phenyl alkyl ethers via catalytic SNAr reactions. The method is applicable to a broad array of electron‐rich and neutral aryl fluorides, which are inert under classical SNAr conditions. Although the mechanism of SNAr reactions involving metal arene complexes is hypothesized to involve a stepwise pathway (addition followed by elimination), experimental data that support this hypothesis is still under exploration. Mechanistic studies and DFT calculations suggest either a stepwise or stepwise‐like energy profile. Notably, we isolated a rhodium η5‐cyclohexadienyl complex intermediate with an sp3‐hybridized carbon bearing both a nucleophile and a leaving group.

Catalytic SN Ar Hydroxylation and Alkoxylation of Aryl Fluorides.

Nucleophilic aromatic substitution (SN Ar) is a powerful strategy for incorporating a heteroatom into an aromatic ring by displacement of a leaving group with a nucleophile, but this method is limited to electron-deficient arenes. We have now established a reliable method for accessing phenols and phenyl alkyl ethers via catalytic SN Ar reactions. The method is applicable to a broad array of electron-rich and neutral aryl fluorides, which are inert under classical SN Ar conditions. Although the mechanism of SN Ar reactions involving metal arene complexes is hypothesized to involve a stepwise pathway (addition followed by elimination), experimental data that support this hypothesis is still under exploration. Mechanistic studies and DFT calculations suggest either a stepwise or stepwise-like energy profile. Notably, we isolated a rhodium η5 -cyclohexadienyl complex intermediate with an sp3 -hybridized carbon bearing both a nucleophile and a leaving group.

Ruthenium-catalyzed Suzuki coupling of anilines with alkenyl borates via selective aryl C[sbnd]N bond cleavage

Herein, we developed a new ruthenium(0)-catalyzed Suzuki-coupling of N,N-dimethyl-2-(pyridin-2-yl) anilines with alkenyl borates to synthesize 2-phenylolefins via the cleavage of neutral aryl CN bond. In the absence of ligand and additives, by using pyridine as the directing group, the desired 2-phenylolefins were obtained in good to excellent yields with high stereoselectivity (E/Z > 20:1).

Diarylmethanols Synthesis by Nickel(II)-catalyzed Addition of Arylboronic Acids to Aryl Aldehydes

A practical procedure for the addition of arylboronic acids to aromatic aldehydes has been developed in the presence of NiCl2(PPh3)2/1,3-bis-(2,6-diisopropylphenyl)imidazolium chloride (IPr·HCl) system with good yield. Generally, electron-rich and -neutral aryl aldehydes showed excellent reactivity and provided desired products in high yields. This procedure will provide new way to the synthesis of diarylmethanols.

Cu-catalyzed N-3-Arylation of Hydantoins Using Diaryliodonium Salts.

A general Cu-catalyzed, regioselective method for the N-3-arylation of hydantoins is described. The protocol utilizes aryl(trimethoxyphenyl)iodonium tosylate as the arylating agent in the presence of triethylamine and a catalytic amount of a simple Cu-salt. The method is compatible with structurally diverse hydantoins and operates well with neutral aryl groups or aryl groups bearing weakly donating/withdrawing elements. It is also applicable for the rapid diversification of pharmaceutically relevant hydantoins.

Ruthenium-Catalyzed Carbonylative Coupling of Anilines with Organoboranes by the Cleavage of Neutral Aryl C–N Bond

Herein, we report the first ruthenium-catalyzed Suzuki-type carbonylative reaction of electronically neutral anilines via C(aryl)-N bond cleavage. Without any ligand and base, diaryl ketones can be obtained in moderate to high yields by using Ru3(CO)12 as the catalyst and chelation assisted by pyridine. The pyridine ring has a significant effect on both high efficiency and high regioselectivity in the cleavage of the aryl C-N bond in anilines.

Pd-Catalyzed C-N Coupling Reactions Facilitated by Organic Bases: Mechanistic Investigation Leads to Enhanced Reactivity in the Arylation of Weakly Binding Amines.

The ability to use soluble organic amine bases in Pd-catalyzed C-N cross-coupling reactions has provided a long-awaited solution to the many issues associated with employing traditional, heterogeneous reaction conditions. However, little is known about the precise function of these bases in the catalytic cycle and about the effect of variations in base structure on catalyst reactivity. We used 19F NMR to analyze the kinetic behavior of C-N coupling reactions facilitated by different organic bases. In the case of aniline coupling reactions employing DBU, the resting state was a DBU-bound oxidative addition complex, LPd(DBU)(Ar)X, and the reaction was found to be inhibited by base. In general, however, depending on the binding properties of the chosen organic base, increased concentration of the base can have a positive or negative influence on the reaction rate. Furthermore, the electronic nature of the aryl triflate employed in the reaction directly affects the reaction rate. The fastest reaction rates were observed with electronically neutral aryl triflates, while the slowest were observed with highly electron-rich and -deficient substrates. We propose a model in which the turnover-limiting step of the catalytic cycle depends on the relative nucleophilicity of the base compared to that of the amine. This hypothesis guided the discovery of new reaction conditions for the coupling of weakly binding amines, including secondary aryl amines, which were unreactive nucleophiles in our original protocol.

Cation-π Interactions in the Benzylic Arylation of Toluenes with Bimetallic Catalysts.

A method to directly arylate toluene derivatives with aryl bromides to generate diarylmethanes, which are important building blocks in drug discovery, is described. In this method, KN(SiMe3)2 in combination with a (NIXANTPHOS)Pd catalyst accomplished the deprotonative activation of toluene derivatives to permit cross-coupling with aryl bromides. Good to excellent yields are obtained with a range of electron-rich to neutral aryl bromides. Both electron-rich and electron-poor toluene derivatives are well tolerated, and even 2-chlorotoluene performs well, providing a platform for introduction of additional functionalization. This discovery hinges on the use of a main group metal to activate toluene for deprotonation by means of a cation-π interaction, which is secured by a bimetallic K(NIXANTPHOS)Pd assembly. Mechanistic and computational studies support acidification of toluene derivatives by the K+-cation- π interaction, which may prove pertinent in the development of other, new reaction systems.

Theoretical insight into the interaction between SnX2 (X = H, F, Cl, Br, I) and benzene.

For a series of five model complexes composed of a singlet SnX2 molecule (X = H, F, Cl, Br, I) and a benzene molecule, the first-principles calculations of their energetics and the analysis of their electron density topology have been performed. The CCSD(T)/CBS interaction energy between SnX2 and C6H6 fall into the range between −10.0 and −11.2 kcal/mol, which indicates that the complexes are rather weakly bound. The relevant role of electrostatic and dispersion contributions to the interaction energy between SnX2 and C6H6 is highlighted in the results obtained from the symmetry-adapted perturbation theory (SAPT). The electron density topological analysis has been carried out using the quantum theory of atoms in molecules (QTAIM) and the noncovalent interactions (NCI) visualization index. Both QTAIM and NCI prove the closed-shell, noncovalent and attractive character of the interaction. A very small charge transfer from C6H6 to SnX2 has been detected. The formation of the five complexes is accompanied by the electron density deformations that are spatially restricted mostly to the region around the Sn atom and its adjacent C atom. The results presented in this work shed some light on the nature of the interactions associated with crystalline structural motifs involving low-valent tin complexed with neutral aryl rings.Electronic supplementary materialThe online version of this article (doi:10.1007/s00894-016-3053-6) contains supplementary material, which is available to authorized users.

ChemInform Abstract: Enantioselective N‐Allylic Alkylation of N‐Propargylsulfonamides with Morita—Baylis—Hillman Carbonates and Sequential Electrophilic Cyclization.

The enantioselective N-allylic alkylation of N-propargylsulfonamides with racemic Morita–Baylis–Hillman (MBH) carbonates catalyzed by modified cinchona alkaloids has been investigated. The alkylation products from MBH carbonates with a 4-methoxyphenyl group underwent ipso-iodocyclization to give optically active azaspirocyclohexadienones via electrophilic activation of alkyne group with iodine monochloride. In contrast, ortho-selective intramolecular Friedel–Crafts reaction occurred for intermediates from MBH carbonates with other electron-rich or neutral aryl or heteroaryl substitutions via the same activation strategy, delivering multifunctional 2-benzazepine frameworks in a highly enantioenriched­ form.

Acyl chloride carbon insertion into dicarbaborane cages – new route to tricarbollide cages

Abstract Reactions between the arachno-6,9-C2B8H14 dicarbaborane and acyl chlorides, RCOCl, in the presence of amine bases in CH2Cl2, followed by acidification with conc. H2SO4 at 0 °C, generate in high yields a series of neutral alkyl and aryl tricarbollides of structure 8-R-nido-7,8,9-C3B8H11 (where R=alkyls and aryls). These skeletal alkylcarbonation (SAC) reactions are consistent with an aldol-type condensation between the RCO group and open-face dicarbaborane hydrogen atoms, which is associated with the insertion of the acyl chloride RC unit into the structure under elimination of three extra hydrogen atoms as H2O and HCl. The reactions thus result in an effective cross-coupling between R and the tricarbollide cage. High-temperature reactions between 8-Ar-nido-7,8,9-C3B8H11 (where Ar=Ph, 1-C10H7, and 2-C10H7) compounds and [CpFe(CO)2]2 produced the first types of monoaryl substituted twelve-vertex ferratricarbollide complexes of general constitution [1-(CpFe)-closo-ArC3B8H10] with three different arrangements of cluster carbon vertexes. The Fe-complexation is accompanied by extensive rearrangement of the cluster carbon atoms over the twelve-vertex cage and the complexes isolated can be regarded as ferrocene analogues.

Enantioselective N-Allylic Alkylation of N-Propargylsulfonamides with Morita­–Baylis–Hillman Carbonates and Sequential Electrophilic Cyclization

The enantioselective <i>N</i>-allylic alkylation of <i>N</i>-propargylsulfonamides with racemic Morita–Baylis–Hillman (MBH) carbonates catalyzed by modified cinchona alkaloids has been investigated. The alkylation products from MBH carbonates with a 4-methoxyphenyl group underwent <i>ipso</i>-iodocyclization to give optically active azaspirocyclohexadienones via electrophilic activation of alkyne group with iodine monochloride. In contrast, <i>ortho</i>-selective intramolecular Friedel–Crafts reaction occurred for intermediates from MBH carbonates with other electron-rich or neutral aryl or heteroaryl substitutions via the same activation strategy, delivering multifunctional 2-benzazepine frameworks in a highly enantioenriched­ form.

Functionalized α-keto stabilized sulfonium ylides as highly active ligand precursors for palladium catalyzed Suzuki–Miyaura cross-couplings

Five α-keto stabilized sulfonium ylides as type (Me)2SCHC(O)C6H4-p-X (X=H, Br, NO2, CH3 and OCH3) {L1–L5} were used as ligand precursors in the Suzuki–Miyaura cross-coupling reaction. The best catalytic performance was obtained by using a sulfonium ylide/Pd ratio of 2:1. The catalytic systems displayed high activities, which increased in the order R=NO2 (L3)<Br (L2)<H (L1)<CH3 (L4)<OCH3 (L5). The coupling reactions proceeded smoothly with 0.05mol% PdCl2 and 0.1mol% L5 in DMF at 130°C between varieties of electronically activated, deactivated and neutral aryl halides and aryl boronic acids within short reaction times and without the need for exclusion of air which gave good to high yields of the corresponding products. All the studied ligands demonstrated very high activity in the Suzuki–Miyaura cross-coupling, which yielded turnover numbers up to 1940. Comparative studies showed that the performance of sulfonium ylide L5 is significantly superior to that of related phosphine-free ligands.

An efficient continuous flow approach to furnish furan-based biaryls.

Suzuki cross-couplings of 5-formyl-2-furanylboronic acid with activated or neutral aryl bromides were performed under continuous flow conditions in the presence of (Bu)4N(+)F(-) and the immobilised t-butyl based palladium catalyst CatCart™ FC1032™. Deactivated aryl bromides and activated aryl chlorides were cross-coupled with 5-formyl-2-furanylboronic in the presence of (Bu)4N(+)OAc(-) using the bis-triphenylphosphine CatCart™ PdCl2(PPh3)2-DVB. Initial evidence indicates the latter method may serve as a universal approach to conduct Suzuki cross-couplings with the protocol successfully employed in the synthesis of the current gold standard Hedgehog pathway inhibitor LDE225.

Copolymerization of Ethylene with Norbornene by Neutral Aryl Phosphine Sulfonate Palladium Catalyst

Complex [Pd(κ2-P,O-{2-(2-MeOC6H4)2P}C6H4SO3)Me(dmso)] (1) was investigated as a single component catalyst for the copolymerization of ethylene with norbornene affording P(E-co-N) in excellent yields and molar masses significantly higher than those of polyethylene. Copolymer molar masses increased with N concentration. Determination of microstructure and reactivity ratios revealed a strong inherent tendency to form alternating copolymers. The ability of palladium complex 1 to effectively copolymerize ethylene with functionalized norbornene derivatives was also demonstrated.

Mg-Catalyzed Dynamic Asymmetric Synthesis of Chiral Pyrrolidines

The Mg-catalyzed enantioselective synthesis of 2,5-cis-disubstituted pyrrolidines 3 is reported via a dynamic kinetic asymmetric [3+2] annulation of racemic cyclopropanes 1 with (E)-imines 2. Extensive optimization of the imine N-protecting group showed that the 2-methoxybenzyl substituent gave the best yield and stereoselectivity. Electron-rich and -neutral aryl imines provided high yields and enantioselectivities of pyrrolidines 3. Electron-poor aryl, alkenyl, and ­aliphatic imines were not competent coupling partners. Electron-rich donor groups (R¹) are also required. Based on mechanistic studies and stereochemical observations, reaction of the imine through the E-geometry via an unusual diaxial transition state is suggested.

ChemInform Abstract: A Convenient One-Pot Preparation of Nitriles from Aldoximes Using 2,2′- Oxalyldi(o-sulfobenzimide).

Under essentially neutral conditions, alkyl, aryl, and heteroaryl aldoximes (4) readily react with 2, 2'-oxalyldi(o-sulfobenzimide) (ODS; 6) in refluxing acetonitrile to give the corresponding nitriles (5) in good yields.

Ionic outgassing from photoacid generators upon irradiation at 13.5 nm

Photoresist outgassing is considered a possible source of contamination of optics in extreme ultraviolet (EUV) lithography at 13.5 nm. We measured the relative proportions of ionic outgassing from 18 commercially available photoacid generators (PAG), which is a key component of chemically amplified photoresists, upon irradiation at 13.5 nm. These PAG include 17 triarylsulfonium or diaryliodonium salts, which contain CF 3 SO 3 - or C 4 F 9 SO 3 - as the anion, and one PAG of molecular type. The overall outgassed ions in the range 10–200 u were counted in relative proportions. Outgassing of F + is found to be dominant, and for most PAG the extent of F + outgassing shows a satisfactory correlation with the ratio of F atomic photoabsorption to the overall PAG photoabsorption. Outgassed ions F +, CF +, CF 2 + and CF 3 + from PAG containing the CF 3 SO 3 - anion and additional C x F y + such as C 2 F 4 + , C 2 F 5 + and C 3 F 5 + from those containing C 4 F 9 SO 3 - are identified. Triphenylsulfonium perfluoro-1-butanesulfonate is one PAG to emit the most abundant F + and total ionic fragments, and a PAG of molecular type ( N-hydroxy-5-norbornene-2,3-dicarboximide perfluoro-1-butanesulfonate) also emits abundantly both hydrocarbon ions and F +. Ionic outgassing of PAG cations includes (C 6H 5) 2S + from R(C 6H 5) 2S + salts and I + from diaryliodonium salts. For PAG containing t-C 4H 9, significantly less F + outgassing is observed; additional outgassing pathways are proposed. The pressure rise caused by PAG shows no dependence on the anion identity, but is correlated with cation photoabsorption, and ascribed to neutral aryl outgassing. Other minor outgassing species include HSO 2 + from sulfonates; C 11 H 9 + and ‘photostable’ PAH cations C 12 H 8 + are identified for the first time and provide evidence of concurrent outgassing from, and polymerization of, PAG upon irradiation at 13.5 nm.

Synthesis, Structural and Photophysical Evaluations of Urea Based Fluorescent PET Sensors for Anions

The design, synthesis and photophysical evaluation of four anthracene based photoinduced electron transfer (PET) sensors (3a–d) for anions is described. The [4π+4π] photodimerization product, 4, was also obtained from 3b, by slow evaporation from DMSO solution and its X-ray crystal structure determined. The structure of 4 showed the classical dimerization at the 9,10-positions of anthracene. Sensors 3a–d are all based on the use of charge neutral aryl urea receptors, where the recognition of anions such as acetate, phosphate and iodide, was due to the formation of strong hydrogen bonding interactions in DMSO. This anion recognition resulted in enhanced quenching of the anthracene excited state via electron transfer from the receptor; hence the emission was ‘switched on–off’. The sensing of fluoride was, however, found to be a two-step process, which involved initial hydrogen bonding interactions with the receptor, followed by deprotonation and the formation of bifluoride (). The changes in the emission spectra upon sensing of chloride and bromide were, however, minor. The photophysical properties of these sensors in the presence of various anions were further studied, including investigation of their excited state lifetimes and quantum yields, as well as detailed Stern–Volmer kinetic analysis with the aim of determining the dynamic and static quenching constants, k q and k s for the above anion recognition. These measurements indicated that while the anion dependant quenching was mostly by a dynamic process, some contribution from static quenching was also observed at lower anion concentrations.