Nucleophilic Aromatic Addition Research Articles

Synthesis and Photophysical Properties of a Series of Novel Porphyrin Dendrimers Containing Organoiron Complexes

This article is focused on the design and photophysical properties of a series of novel porphyrin and metalloporphyrin dendrimers containing cationic η6-chloroarene-η5-cyclopentadienyliron(II) complexes functionalized with naphthalene and capped with ferrocene. The incorporation of cationic η6-chloroarene-η5-cyclopentadienyliron moieties into the dendrimer structures enhances solubility, and facilitates nucleophilic aromatic substitution and addition reactions due to the intense electron-withdrawing ability of the iron center. Divergent approaches were employed to yield highly symmetrical branched materials, with interesting and potentially useful properties. The preparation of these dendrimers was achieved via metal-mediated nucleophilic aromatic substitutions and Steglich esterifications. These dendrimers and their precursors were characterized through nuclear magnetic resonance spectroscopy, infrared spectroscopy, and UV–Visible and fluorescence spectroscopy. Substitution on the porphyrin core with various side chains and terminal functional groups and chromophores had little impact on the porphyrin emission properties, allowing for a wide variety of fluorescent macromolecules to be prepared which retain this characteristic emission. Also, the presence or absence of the organopyrene moieties also had little effect on the emission from these compounds. Complexation of a metal cation, such as Zn2+, by these compounds, did however result in a significant blue shift in the observed fluorescence; this interesting result has the potential for applications in the development of fluorescent-based cation sensors.

Nucleophilic Aromatic Addition in Ionizing Environments: Observation and Analysis of New C-N Valence Bonds in Complexes between Naphthalene Radical Cation and Pyridine.

Radical organic ions can be stabilized by complexation with neutral organics via interactions that can resemble chemical bonds, but with much diminished bond energies. Those interactions are a key factor in cluster growth and polymerization reactions in ionizing environments such as regions of the interstellar medium and solar nebulae. Such radical cation complexes between naphthalene (Naph) and pyridine (Pyr) are characterized using mass-selected ion mobility experiments. The measured enthalpy of binding of the Naph+•(Pyr) heterodimer (20.9 kcal/mol) exceeds that of the Naph+•(Naph) homodimer (17.8 kcal/mol). The addition of 1-3 more pyridine molecules to the Naph+•(Pyr) heterodimer gives 10-11 kcal/mol increments in binding enthalpy. A rich array of Naph+•(Pyr) isomers are characterized by electronic structure calculations. The calculated Boltzmann distribution at 400 K yields an enthalpy of binding in reasonable agreement with experiment. The global minimum is a distonic cation formed by Pyr attack on Naph+• at the α-carbon, changing its hybridization from sp2 to distorted sp3. The measured collision cross section in helium for the Naph+•(Pyr) heterodimer of 84.9 ± 2.5 Å2 at 302 K agrees well with calculated angle-averaged cross sections (83.9-85.1 Å2 at 302 K) of the lowest energy distonic structures. A remarkable 16 kcal/mol increase in the binding energy between Naph+•(Pyr) and Bz+•(Pyr) (Bz is benzene) is understood by energy decomposition analysis. A similar increase in binding from Naph+•(NH3) to Naph+•(Pyr) (as well as between Bz+•(NH3) and Bz+•(Pyr)) is likewise rationalized.

Exploiting Solvate Ionic Liquids for Amine Gas Analysis on a Quartz Crystal Microbalance.

We demonstrated in this work the usefulness of solvate ionic liquids SIL 3 and SIL 4 for chemoselective detection of amine gases on a quartz crystal microbalance. This detection of gaseous amines was achieved by nucleophilic aromatic addition reactions with super electrophilic SIL 3 or SIL 4 thin-coated on quartz chips. Starting with inexpensive reagents, functional SIL 3 and SIL 4 could be readily synthesized in two short steps with high isolated yield (81 and 77%, respectively). The QCM platform developed in this work is readily applicable and highly sensitive to low molecular weight amine gases: for propylamine gas at 10 Hz decrease in resonance frequency, the sensitivity of detection using SIL 4 was 5.4 ppb. This simple and convenient assembly of neutral ligands (e.g., 1a and 1b) with Li+ ion to afford room temperature ionic liquids should be of great importance for a myriad of applications. To the best of our knowledge, no example to date of reports based on nucleophilic aromatic addition reactions demonstrating sensitive amine gas detection in solvate ionic liquids on a QCM has been reported. Furthermore, because of the high color intensity of the Meisenheimer complexes formed, our preliminary result showed that SIL 4 loaded on copier paper can be used not only as a portable amine gas sensor but also as a potential invisible ink that is only revealed by amine vapor.

Lewis Acid Activation of Pyridines for Nucleophilic Aromatic Substitution and Conjugate Addition

A clean, mild and sustainable method for the functionalization of pyridines and their analogues is reported. A zinc-based Lewis acid is used to activate pyridine and its analogues towards nucleophilic aromatic substitution, conjugate addition, and cyclization reactions by binding to the nitrogen on the pyridine ring and activating the pyridine ring core towards further functionalization.

Gas Phase Reactions of 1,3,5-Triazine: Proton Transfer, Hydride Transfer, and Anionic σ-Adduct Formation

The gas phase reactivity of 1,3,5-triazine with several oxyanions and carbanions, as well as amide, was evaluated using a flowing afterglow-selected ion flow tube mass spectrometer. Isotopic labeling, H/D exchange, and collision induced dissociation experiments were conducted to facilitate the interpretation of structures and fragmentation processes. A multi-step (→ HCN + HC(2)N (2) (-) → CN(-) + 2 HCN) and/or single-step (→ CN(-) + 2 HCN) ring-opening collision-induced fragmentation process appears to exist for 1,3,5-triazinide. In addition to proton and hydride transfer reactions, the data indicate a competitive nucleophilic aromatic addition pathway (S(N)Ar) over a wide range of relative gas phase acidities to form strong anionic σ-adducts (Meisenheimer complexes). The significant hydride acceptor properties and stability of the anionic σ-adducts are rationalized by extremely electrophilic carbon centers and symmetric charge delocalization at the electron-withdrawing nitrogen positions. The types of anion-arene binding motifs and their influence on reaction pathways are discussed.

ChemInform Abstract: Cyclization of Deprotonated 2-Phenyl-1-tosylaziridine. A Surprising Example of an Intramolecular Nucleophilic Aromatic Addition.

Abstract Deprotonation of 2-phenyl-1-tosylaziridine 1 with butyl lithium gives an anion that cyclizes to 4 by an intramolecular nucleophilic aromatic addition. Treatment of derivatives 5, 6 with a Grignard reagent produces aziridines 10, 11 .

Nucleophilic Aromatic Addition Reactions of the Metallabenzenes and Metallapyridinium: Attacking Aromatic Metallacycles with Bis(diphenylphosphino)methane to Form Metallacyclohexadienes and Cyclic η2-Allene-Coordinated Complexes

The reactions of phosphonium-substituted metallabenzenes and metallapyridinium with bis(diphenylphosphino)methane (DPPM) were investigated. Treatment of [Os{CHC(PPh(3))CHC(PPh(3))CH}Cl(2)(PPh(3))(2)]Cl with DPPM produced osmabenzenes [Os{CHC(PPh(3))CHC(PPh(3))CH}Cl(2){(PPh(2))CH(2)(PPh(2))}]Cl (2), [Os{CHC(PPh(3))CHC(PPh(3))CH}Cl{(PPh(2))CH(2)(PPh(2))}(2)]Cl(2) (3), and cyclic osmium eta(2)-allene complex [Os{CH=C(PPh(3))CH=(eta(2)-C=CH)}Cl(2){(PPh(2))CH(2)(PPh(2))}(2)]Cl (4). When the analogue complex of osmabenzene 1, ruthenabenzene [Ru{CHC(PPh(3))CHC(PPh(3))CH}Cl(2)(PPh(3))(2)]Cl, was used, the reaction produced ruthenacyclohexadiene [Ru{CH=C(PPh(3))CH=C(PPh(3))CH}Cl{(PPh(2))CH(2)(PPh(2))}(2)]Cl(2) (6), which could be viewed as a Jackson-Meisenheimer complex. Complex 6 is unstable in solution and can easily be convert to the cyclic ruthenium eta(2)-allene complexes [Ru{CH=C(PPh(3))CH=(eta(2)-C=CH)}Cl{(PPh(2))CH(2)(PPh(2))}(2)]Cl(2) (7) and [Ru{CH=C(PPh(3))CH=(eta(2)-C=CH)}Cl(2){(PPh(2))CH(2)(PPh(2))}(2)]Cl (8). The key intermediates of the reactions have been isolated and fully characterized, further supporting the proposed mechanism for the reactions. Similar reactions also occurred in phosphonium-substituted metallapyridinium [OsCl(2){NHC(CH(3))C(Ph)C(PPh(3))CH}(PPh(3))(2)]BF(4) to give the cyclic osmium eta(2)-allene-imine complex [OsCl(2){NH=C(CH(3))C(Ph)=(eta(2)-C=CH)}{(PPh(2))CH(2)(PPh(2))}(PPh(3))]BF(4) (11).

Synthesis of Polycyclic Cyclohexadienyl Ruthenium(II) Complexes from η6-Arene Precursors via Phosphine-Promoted Intramolecular Nucleophilic Aromatic Addition

An experimentally straightforward procedure for the synthesis of structurally elaborate cyclohexadienyl ruthenium(II) complexes has been developed along the lines of the Morita−Baylis−Hillman reaction. Coordination of (cyclopentadienyl)Ru(II) fragments to N-benzyl and N-phenethyl acrylamides was found to facilitate conversion to stable cyclohexadienyl complexes via Bu3P-mediated intramolecular cyclization. An ipso cyclization was observed in all but one case, resulting in formation of five- or six-membered spirolactams at C6 positions of cyclohexadienyl ligands. Acrylamides prepared from dihydroindene and tetrahydronaphthalene precursors were suitable substrates for this transformation, affording access to novel tricyclic cyclohexadienyl complexes. One such complex was characterized by X-ray crystallography.

Metal-mediated dearomatization leading to 2-azaspiro[4.5]decanes via tandem nucleophilic aromatic addition–Horner–Wadsworth–Emmons olefination–oxidative demetalation sequences

A ruthenium-mediated dearomatization sequence has been developed that delivers structurally intriguing azaspirolactam products in stereoselective fashion. Treatment of (η 6-arene)Ru(cyclopentadienyl) complexes bearing N-benzyl-β-amido phosphonate side chains with excess NaH results in intramolecular nucleophilic aromatic addition to the ipso position of the coordinated arenes. Subsequent Horner–Wadsworth–Emmons (HWE) reaction with added aldehydes affords olefinated spirolactam cyclohexadienyl ruthenium complexes. Mild oxidation with CuCl 2 or CuBr 2 under CO effects removal and recovery of the CpRu(II) fragment. Substituents present on the cyclohexadienyl skeleton influence the outcome of demetalation and products obtained in this study include functionalized 2-azaspiro[4.5]decanes and tetrahydroisoquinolinones.

Nucleophilic Addition of Organometallic Reagents to Cinchona Alkaloids: Simple Access to Diverse Architectures

Aminal pharm: Grignard reagents undergo a surprising nucleophilic aromatic addition reaction to cinchona alkaloids to stereoselectively produce cyclic aminals. Structurally diverse alkaloid derivatives with rigid cores that bear reactive functional groups (see examples) can be readily synthesized by this simple nucleophilic alkylation protocol.

Recent Progress in Diaryl Ether Synthesis

Diaryl ethers form an important class of organic compounds, both in life sciences and in the polymer industry. In general, diaryl ethers can be synthesized by means of copper-catalyzed Ullmann diaryl ether coupling, palladium-catalysed Buchwald-Hartwig reaction, nucleophilic aromatic substitution, arylboronic acid diaryl ether coupling, oxidative coupling, and nucleophilic aromatic addition to metal-arene complexes. This review covers the progress in diaryl ether synthesis since 1999, with literature coverage through September 2005.

Exploiting Phosphonate Chemistry in Metal-Mediated Dearomatization: Stereoselective Construction of Functionalized Spirolactams from Arene Ruthenium Complexes

Arene ruthenium complexes possessing beta-amido phosphonate side chains participate in intramolecular spirocyclization reactions to deliver stable cyclohexadienyl ruthenium adducts. Spirocyclization is accomplished via a tandem two-step sequence that involves stereoselective nucleophilic aromatic addition to the ipso position of the coordinated arene, followed by intermolecular Horner-Wadsworth-Emmons olefination. The resulting eta5-cyclohexadienyl complexes can then be diastereoselectively converted to metal-free azaspiro[4.5]decane derivatives upon oxidative demetalation in the presence of suitable nucleophiles. An asymmetric spirocyclization was demonstrated through application of this procedure to a beta-amido phosphonate prepared from (S)-(-)-alpha-methyl benzylamine. The expected spirolactam product was obtained as a single enantiomer.

Human Glutathione Transferase A1-1 Demonstrates Both Half-of-the-sites and All-of-the-sites Reactivity

A study of the kinetics of a heterodimeric variant of glutathione transferase (GST) A1-1 has led to the conclusion that, although the wild-type enzyme displays all-of-the-sites reactivity in nucleophilic aromatic substitution reactions, it demonstrates half-of-the-sites reactivity in addition reactions. The heterodimer, designed to be essentially catalytically inactive in one subunit due to a single point mutation (D101K), and the two parental homodimers were analyzed with seven different substrates, exemplifying three types of reactions catalyzed by glutathione transferases (nucleophilic aromatic substitution, addition, and double-bond isomerization reactions). Stopped-flow kinetic results suggested that the wild-type GST A1-1 behaved with half-of-the-sites reactivity in a nucleophilic aromatic substitution reaction, but steady-state kinetic analyses of the GST A1-D101K heterodimer revealed that this was presumably due to changes to the extinction coefficient of the enzyme-bound product. In contrast, steady-state kinetic analysis of the heterodimer with three different substrates of addition reactions provided evidence that the wild-type enzyme displayed half-of-the-sites reactivity in association with these reactions. The half-of-the-sites reactivity was shown not to be dependent on substrate size, the level of saturation of the enzyme with glutathione, or relative catalytic rate.

Intramolecular Addition of Stabilized Enolates to (η6-Arene)ruthenium Complexes: Synthesis of Ru-Coordinated Azaspirocycles

Stabilized enolates attached to cationic (arene)RuIICp complexes via an amide linkage were found to participate in nucleophilic aromatic addition reactions resulting in the formation of novel cyclohexadienyl−Ru azaspirocycles. Enolate addition to the activated arene ring was found to proceed with complete stereoselectivity.

Reaction of Benzoic Esters with Organolithium and -magnesium Reagents. Dichotomy between Nucleophilic Aromatic Substitution and Conjugate Addition

The reactions of 2,6-di-tert-butyl-4-methoxyphenyl 2-methoxybenzoate 1a with several organolithium and -magnesium reagents are found to give the methoxy-substitution products 2 and/or the conjugate addition products to the benzoate ring ( 3 and 4 ), preferring the latter products at the expense of the former with the increase of the electron-donating ability of the carbonion species. A SET mechanism is proposed for the conjugate addition. Reactions of benzoates with organolithium and -magnesium reagets lead to nucleophilic aromatic substitution and/or conjugate addition.

Reaction of benzoic esters with organolithium and -magnesium reagents. dichotomy between nucleophilic aromatic substitution and conjugate Addition

The reactions of 2,6-di-tert-butyl-4-methoxyphenyl 2-methoxybenzoate 1a with several organolithium and -magnesium reagents are found to give the methoxy-substitution products 2 and/or the conjugate addition products to the benzoate ring ( 3 and 4), preferring the latter products at the expense of the former with the increase of the electron-donating ability of the carbonion species. A SET mechanism is proposed for the conjugate addition.

Cyclization of deprotonated 2-phenyl-1-tosylaziridine. A surprising example of an intramolecular nucleophilic aromatic addition

Deprotonation of 2-phenyl-1-tosylaziridine 1 with butyl lithium gives an anion that cyclizes to 4 by an intramolecular nucleophilic aromatic addition. Treatment of derivatives 5, 6 with a Grignard reagent produces aziridines 10, 11.

Cationic arenetricarbonylmanganese complexes : nucleophilic aromatic addition

Nucleophilic aromatic addition of α-iminoester or nitrile, α-sulfonyl and α-nitro carbanions to cationic arenetricarbonylmanganese complexes readily occurs with good yield

Nucleophilic aromatic addition. Part IX: A route from 1,3,5‐trinitrobenzene to a dinitro‐tropane derivative

Abstract1,3,5‐Trinitrobenzene takes up three methylene groups from diazomethane at −80° to give 1 (Scheme 1).Reduction of I with NaBH4 in pyridine yields the dihydro derivative II by saturation of the nitro‐olefinic double bond in I.In a protic solvent like methanol, this reaction proceeds with rupture of the isoxazoline‐N‐oxide ring, and leads to the intermediary formation of a nitroso‐and a primary alcohol‐function. The nitroso‐group reacts spontaneously further with a nearby HCNO2‐fragment, and this transannular process generates the tropane ring‐system of III. The hydroxyl‐group at the nitrogen‐bridge is easily oxidised, to give a relatively stable nitroxide, detectable by ESR. Spectral data, including X‐ray analysis of III1 fully confirm the proposed structures.

The low temperature reaction of diazomethane with 1,3,5‐trinitrobenzene: Nucleophilic aromatic addition VIII

AbstractThere is a strong temperature effect on the reaction of 1,3,5‐trinitrobenzene with diazomethane. At 0° three methylene groups are introduced and the product is the trinitro derivative I (found earlier).Below −80°, again three methylene groups are introduced, but the main product is a dinitro compound II, isomeric with I but with strikingly different properties.The methylene groups in II are incorporated in a seven‐membered ring, a cyclopropane ring and an isoxazoline ring, the latter arising by an unusual participation of one of the nitro groups.The structural proof of II rests on spectroscopic evidence and specific chemical reactions.