"Inverse-electron-demand" ligand substitution: experimental and computational insights into olefin exchange at palladium(0)

The mechanism of olefin substitution at palladium(0) has been studied, and the results provide unique insights into the fundamental reactivity of electron-rich late transition metals. A systematic series of bathocuproine-palladium(0) complexes bearing trans-beta-nitrostyrene ligands (ns(X) = X-C(6)H(4)CH=CHNO(2); X = OCH(3), CH(3), H, Br, CF(3)), (bc)Pd(0)ns(X) (3(X)), was prepared and characterized, and olefin-substitution reactions of these complexes were found to proceed by an associative mechanism. In cross-reactions between (bc)Pd(ns(CH)()3) and ns(X) (X = OCH(3), H, Br, CF(3)), more-electron-deficient olefins react more rapidly (relative rate: ns(CF)()3 > ns(Br) > ns(H) > ns(OCH)()3). Density functional theory calculations of model alkene-substitution reactions at a diimine-palladium(0) center reveal that the palladium center reacts as a nucleophile via attack of a metal-based lone pair on the empty pi orbital of the incoming olefin. This orbital picture contrasts that of traditional ligand-substitution reactions, in which the incoming ligand donates electron density into an acceptor orbital on the metal. On the basis of these results, olefin substitution at palladium(0) is classified as an "inverse-electron-demand" ligand-substitution reaction.     

"Oxidatively induced" reductive elimination of dioxygen from an eta2-peroxopalladium(II) complex promoted by electron-deficient alkenes

The first example of associative displacement of dioxygen from a peroxopalladium(II) complex is reported. Electron-deficient alkenes, p-X-trans-beta-nitrostyrene (X = OCH3, CH3, H, F, Br, CF3, NO2), react quantitatively with (bc)Pd(eta2-O2) (bc = bathocuproine) in dichloromethane at room temperature to form the corresponding palladium(0)-alkene complexes. Mechanistic studies indicate that ligand substitution proceeds through an associative mechanism, and the electronic characteristics of the reactions are consistent with an "oxidatively induced" reductive elimination pathway.     

Solid-phase synthesis of asymmetrically substituted "AB3-type" phthalocyanines

Synthesis of phthalocyanines with asymmetrical substitution on the periphery is often difficult due the problems in purification of the phthalocyanine mixtures obtained. Using a poly(ethylene glycol) (PEG)-based support with a Wang-type linker, we have developed the synthesis of monohydroxylated, oligoethylene glycol substituted phthalocyanines utilizing an amidine-base-promoted phthalonitrile tetramerization reaction. The use of a hydrophilic support allows symmetrical phthalocyanine product formed in solution to be readily and completely removed by washing while leaving the "AB3" product on the support. Acid cleavage with 10% trifluoroacetic acid provides the pure unsymmetrically substituted Pc. This method was applied to several metallo Pcs. Additionally, methods to avoid premature reactions on-resin that give A2B2 products are provided.     

2-(2-thienyl)-6-methyl-6<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">g</Emphasis>][1,3]benzothiazole: Synthesis and some transformations

Oxidation of N-(1-methylbenzimidazol-5-yl)thiophene-2-carbothioamide with potassium ferricyanide in an alkaline medium by Jacobson’s method afforded 2-(thien-2-yl)-6-methyl-6H-imidazo[4,5-g][1,3]benzothiazole. The latter enters into the electrophilic substitution reaction (nitration, bromination, formylation, acylation) exclusively at the position 5 of the thiophene ring. Characteristic reactions of nucleophilic substitution occurred at the imidazole ring. Quaternization with methyl iodide in benzene furnished the corresponding quaternary salt, whereas the Chichibabin amination with an excess of sodium amide in xylene gave negative result.     

Reaction of <Emphasis Type="Italic">N</Emphasis>-chloro-1,4-benzoquinone imines with thiols

N-Chloro-1,4-benzoquinone imines reacted with arenethiols to give different products, depending on the conditions and initial quinone imine structure. N-(Arylsulfanyl)-1,4-benzoquinone imines were obtained as a result of nucleophilic substitution of the chlorine atom, and 1,4-benzoquinone imines containing an aryl-sulfanyl substituent in the quinoid ring were formed according to the radical mechanism. The reactions of N-chloro-1,4-benzoquinone imines with heterocyclic thiols afforded only the corresponding chlorine substitution products.     

"One-pot" two-step synthesis of aryl sulfur compounds by photoinduced reactions of thiourea anion with aryl halides

[reaction: see text]. The photoinduced reactions of aryl halides with the thiourea anion afford arene thiolate ions in DMSO. These species without isolation, and by a subsequent aliphatic nucleophilic substitution, S(RN)1 reaction, oxidation, or protonation, yield aryl methyl sulfides, diaryl sulfides, diaryl disulfides, and aryl thiols with good yields (50-80%). This is a simple and convenient approach which involves the use of the commercially available and inexpensive thiourea in a "one-pot" two-step process for the synthesis of aromatic sulfur compounds.     

Synthesis and properties of 2-(furan-2-yl)thiazolo[5,4-<Emphasis Type="Italic">f</Emphasis>]quinoline

N-(Quinolin-6-yl)furan-2-carboxamide was prepared by the coupling of quinoline-6-amine with furan-2-carbonyl chloride in propan-2-ol. Treatment of the product with excess Р2S₅ in anhydrous pyridine gave N-(quinolin-6-yl)furan-2-carbothioamide which was oxidized with potassium ferricyanide in an alkaline medium by the Jakobson procedure to obtain 2-(furan-2-yl)thiazolo[5,4-f]quinoline. The latter was subjected to electrophilic substitution reactions (nitration, bromination, formylation, and acylation), as well as characteristic nucleophilic substitution involving the quinoline ring and quaternization with methyl iodide in benzene.     

Gas-Phase Chemistry of Benzyl Cations in Dissociation of <Emphasis Type="BoldItalic">N</Emphasis>-Benzylammonium and <Emphasis Type="BoldItalic">N</Emphasis>-Benzyliminium Ions Studied by Mass Spectrometry

In this study, the fragmentation reactions of various N-benzylammonium and N-benzyliminium ions were investigated by electrospray ionization mass spectrometry. In general, the dissociation of N-benzylated cations generates benzyl cations easily. Formation of ion/neutral complex intermediates consisting of the benzyl cations and the neutral fragments was observed. The intra-complex reactions included electrophilic aromatic substitution, hydride transfer, electron transfer, proton transfer, and nucleophilic aromatic substitution. These five types of reactions almost covered all the potential reactivities of benzyl cations in chemical reactions. Benzyl cations are well-known as Lewis acid and electrophile in reactions, but the present study showed that the gas-phase reactivities of some suitably ring-substituted benzyl cations were far richer. The 4-methylbenzyl cation was found to react as a Brønsted acid, benzyl cations bearing a strong electron-withdrawing group were found to react as electron acceptors, and para-halogen-substituted benzyl cations could react as substrates for nucleophilic attack at the phenyl ring. The reactions of benzyl cations were also related to the neutral counterparts. For example, in electron transfer reaction, the neutral counterpart should have low ionization energy and in nucleophilic aromatic substitution reaction, the neutral counterpart should be piperazine or analogues. This study provided a panoramic view of the reactions of benzyl cations with neutral N-containing species in the gas phase.     

Preparation and reactivity of 2-(furan-2-yl)acenaphtho[1,2-<Emphasis Type="Italic">d</Emphasis>]oxazole

Reaction of acenaphthylene-1,2-dione and furan-2-carbaldehyde in ethanol with an excess of ammonia water solution afforded 2-(furan-2-yl)acenaphtho[1,2-d]oxazole whose reactions of electrophilic substitution (nitration, bromination, hydroxymethylation, formylation, acylation) were examined. Notwithstanding the reaction conditions the electrophilic attack was directed on the furan ring.     

"Asymmetric" catalysis by lanthanide complexes

Catalysis with lanthanide (Ln) complexes has been underestimated for long time, although Ln(III) complexes have great advantages as Lewis acid catalysts for "asymmetric" carbon-carbon bond-forming reactions. Lanthanide complexes are highly active in ligand-substitution reactions, especially with hard ligands. The association with substrates and dissociation of products are achieved fast enough for high catalyst efficiency. The asymmetric catalysis of organic reactions can be greatly advanced by the use of Ln complexes with chiral ligands such as binaphthol (binol). Ln(II) complexes are good reducing agents, which can be used in a wide variety of synthetically important reactions; when chiral ligands are used, many of these reactions are highly stereoselective. In the context of "green chemistry", the development of asymmetric Ln catalysts, and their recyclable use, is of increasing importance. This review gives an overview of the most recent developments in catalysis with lanthanide(II) and lanthanide(III) complexes.     

The classic "brown-ring" reaction in a new medium: kinetics, mechanism, and spectroscopy of the reversible binding of nitric oxide to iron(II) in an ionic liquid

To elucidate the applicability and properties of ionic liquids (ILs) to serve as chemical reaction media for the activation of small molecules by transition-metal complexes, detailed kinetic and mechanistic studies were performed on the reversible binding of NO to FeCl(2) dissolved in the IL 1-ethyl-3-methylimidazolium dicyanamide ([emim][dca]) as a solvent. We report, for the first time, the application of laser flash photolysis at ambient and high pressure to study the kinetics of this reaction in an IL. The kinetic data and activation parameters for the "on" and "off" reactions suggest that both processes follow a limiting dissociative (D) ligand substitution mechanism, in contrast to that reported for the same reaction in aqueous solution, where this well-known "brown-ring" reaction follows an interchange dissociative (I(d)) ligand substitution mechanism. The observed difference apparently arises from the participation of the IL anion as a N-donor ligand, as evidenced by the formation of polymeric [Fe(dca)(3)Cl](x)[emim](2x) chains in the solid state and verified by X-ray crystallography. In addition, infrared (IR), Mo?ssbauer, and EPR spectra were recorded for the monomeric reaction product [Fe(dca)(5)NO](3-) formed in the IL, and the parameters closely resemble those of the {FeNO}(7) unit in other well-characterized nitrosyl complexes. It is concluded that its electronic structure is best described by the presence of a high-spin Fe(III) (S = 5/2) center antiferromagnetically coupled to NO(-) (S = 1), yielding the observed spin quartet ground state (S(t) = 3/2).     

Synthesis and reactivity of 2-(furan-2-yl)benzo[<Emphasis Type="Italic">e</Emphasis>][1,3]benzothiazole

N-(1-Naphthyl)furan-2-carboxamide was synthesized by the coupling of naphthalen-1-amine with furan-2-carbonyl chloride in propan-2-ol and then treated with excess P2S5 in anhydrous toluene to obtain the corresponding thioamide. The latter was oxidized with potassium ferricyanide in an alkaline medium by the Jakobson procedure to synthesize 2-(furan-2-yl)benzo[e][1,3]benzothiazole which was subjected to electrophilic substitution reactions: nitration, bromination, formylation, and acylation.     

Phosphate esters as "tunable" reagents in organic synthesis

The essential role phosphates have in biochemistry has no parallel in man-made chemistry, where the poor reactivity of these esters towards nucleophilic substitution makes more reactive substrates such as halides and sulfonates preferred. Nevertheless, phosphates are acquiring an increasing role in organic synthesis as long as new activation modes become available. These include metal catalysis and photochemistry (the latter effective with benzyl and aryl derivatives) that may turn the present limitation into a promising opportunity by devising convenient tunable reactions.     

Electrophilic substitution in <Emphasis Type="Italic">meso</Emphasis>-phenylporphyrins

Electrophilic substitution reactions in the meso-phenylporphyrins are described. The relative reactivity of the various positions of the porphyrin cycle to attack by electrophiles was discussed.     

Synthesis and properties of (thieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridin-3-yl)iminotriphenylphosphoranes. Molecular structure of (2-benzoyl-4-methoxymethyl-6-methylthieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridin-3-yl)iminotriphenylphosphorane

Iminophosphoranes containing a thieno[2,3-b]pyridine fragment were obtained through a sequence of reactions: 1) alkylation of 3-cyano-2(1H)-pyridinethiones in alkaline medium by an -halocarbonyl compound with subsequent Thorpe-Ziegler cyclization of the resultant 2-thioalkylpyridines to give 3-aminothieno[2,3-b]pyridines, 2) diazotization of the amino group and nucleophilic substitution of the diazonium group by an azido group without isolation of the diazonium salts, and 3) reaction of the 3-azidothieno[2,3-b]pyridines with triphenylphosphine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1853–1862, December, 2004.     

A "click and activate" approach in one-pot synthesis of a triazolyl-pyridazinone library

A "click and activate" strategy was designed and executed in a four-component, stepwise condensation that led to a trisubstituted triazolyl-pyridazinone library. This one-pot process included regioselective azide substitution at 2-substituted-4,5-dichloropyridazinones, followed by a Cu(I) catalyzed triazole formation which triggered subsequent nucleophilic substitution at the neighboring position to achieve three points of diversity.     

Reactions of diphenyldithiophosphinic acid with <Emphasis Type="Italic">N</Emphasis>-alkyl-2-chloro-2-methylpropanimines

In contrast to O,O-dialkyldithiophosphoric acids, the reactions of more weak diphenyldithiophosphinic acid with N-alkyl-2-chloro-2-methylpropanimines at a 1 : 1 reagent ratio follow two pathways. The first route is nucleophilic substitution of the chlorine atom of the initially formed iminium salt with the diphenylthiophosphinylthio moiety and the second route is the reduction of the C–Cl bond of this iminium salt cation. The main reaction direction is nucleophilic substitution producing new iminium salts, namely, N-alkyl-2-(di phenyl thiophosphinylthio)-2-methylpropaniminium chlorides. These salts were used as the starting material to synthesize new organophosphorus compounds bearing aldehyde, imine, and acetal groups and 1,3-diazolidine cycle.     

The nucleophilic substitution reaction for [18F]fluoride-ion on the series of N6-benzoyl-2",3"-isopropylideneadenosine-5"-sulfonates

The reaction of the nca [¹⁸F]fluoride ion was investigated toward a series of N⁶-benzoyl 2",3"-isopropylidene-adenosine-5"-sulfonates including the methane-(mesylate), p-toluene-(tosylate), p-nitro-benzene-(nosylate)- and 2,2,2-trifluoro-ethane-sulfonate (tresylate) derivatives under usual nucleophilic substitution conditions. In these reactions cyclisation of the title compounds was observed whilst the radiofluorination took place only with low yield. The fluorine-18 uptake was found to be 1.17% for mesylate, 1.46% for tosylate, 0.99% for nosylate and 0.40% for tresylate under the conditions applied.     

Electron transfer in supercritical carbon dioxide: ultraexothermic charge recombination at the end of the "inverted region"

Charge-recombination rates in contact radical-ion pairs, formed between aromatic hydrocarbons and nitriles in supercritical CO(2) and heptane, decrease with the exothermicity of the reactions until they reach -70 kcal mol(-1), but from there on an increase is observed. The first decrease in rate is typical of the "inverted region" of electron-transfer reactions. The change to an increase in the rate for ultra-exothermic electron transfer indicates a new free-energy relationship. We show that the resulting "double-inverted region" is not due to a change in mechanism. It is an intrinsic property of electron-transfer reactions, and it is due to the increase of the reorganisation energy with the reaction exothermicity.     

Synthesis and properties of 2,5-bis(furan-2-yl)-1<Emphasis Type="Italic">H</Emphasis>-imidazole

2,5-Bis(furan-2-yl)-1H-imidazole was synthesized by the Weidenhagen reaction of [2-(furan-2-yl)-2-oxoethyl]acetate with furfural. Alkylation of the title compound with methyl iodide in acetone in the presence of potassium hydroxide gave a mixture of isomeric N-methyl derivatives, 2,5-bis(furan-2-yl)-1-methyl-1H-imidazole being the major one. Electrophilic substitution reactions of the latter (nitration, bromination, sulfonation, hydroxymethylation, and acylation) were studied.