Singlet molecular oxygen trapping by the fluorescent probe diethyl-3,3 '-(9,10-anthracenediyl)bisacrylate synthesized by the Heck reaction

Singlet molecular oxygen O(2)((1)Delta(g)) is a potent oxidant that can react with different biomolecules, including DNA, lipids and proteins. Many polycyclic aromatic hydrocarbons have been studied as O(2)((1)Delta(g)) chemical traps. Nevertheless, a suitable modification in the polycyclic aromatic ring must be made to increase the yield of O(2)((1)Delta(g)) chemical trapping. With this goal, an anthracene derivative, diethyl-3,3 '-(9,10-anthracenediyl)bisacrylate (DADB), was obtained from the reaction of 9,10-dibromoanthracene and ethyl acrylate through the Heck coupling reaction. The coupling of ethyl acrylate with the anthracene ring produced a new lipophilic, esterified, fluorescent probe reactive toward O(2)((1)Delta(g)). This compound reacts with O(2)((1)Delta(g)) at a rate of k(r) = 1.69 x 10(6) M(-1) s(-1) forming a stable endoperoxide (DADBO(2)), which was characterized by UV-Vis, fluorescence, HPLC/MS and (1)H and (13)C NMR techniques. The photophysical, photochemical and thermostability features of DADB were also evaluated. Furthermore, this compound has the potential for great application in biological systems because it is easily synthetized in large amount and generates specific endoperoxide (DADBO(2)), which can be easily detected by HPLC tandem mass spectrometry (HPLC/MS/MS).

alpha-Arylation and Alkynylation of Cyclic alpha-Iodoenones Using Palladium-Catalyzed Cross-Coupling Reactions with Trifluoroborate Salts

An expeditious synthesis of alpha-aryl- and alpha-alkynylcyclo-hexenones is described and illustrated by palladium-catalyzed cross-coupling reaction of cyclic alpha-iodoenones with potassium aryltrifluoroborate salts. This procedure offers easy access to alpha-arylated and alkynylated cyclohexenones functionalized with electrondonor and -acceptor substituents in good yields.

Synthesis of symmetrical 1,3-diynes via homocoupling reaction of n-butyl alkynyltellurides

An ultrasound-assisted synthesis of symmetrical 1,3-diyne compounds with electron-withdrawing or donating substituents is described and illustrated by the palladium-catalyzed homocoupling reaction of n-butyl alkynyltellurides. This procedure offers easy access to 1,3-diynes in very short reaction times, and the products are achieved in good to excellent yields. (C) 2009 Elsevier Ltd. All rights reserved.

Arylation of β,γ-unsaturated lactones by a Heck-Matsuda reaction: an unexpected route to aryldiazene butenolides and pyridazinones

The palladium catalysed coupling of aryldiazonium salts with β-γ-unsaturated lactones under basic conditions has been investigated. Both (3H)-furanone and α-angelicalactone were evaluated as substrates in the Heck Matsuda reaction but both failed to afford the desired arylated butenolides. Under basic conditions, β-γ-unsaturated lactones generate highly nucleophilic enolates that preferentially undergo azo coupling reactions with arenediazonium salts to afford aryldiazene butenolides. The electronic and steric effect of the substituents on the aryldiazonium salt in the azo coupling reaction is described. Aryldiazene-lactone derivatives were obtained in good yields from a highly facile and straightforward procedure. An aminoisomaleimide was formed from (3H)-furanone and cyclised to the corresponding pyridazinones in modest yield.

Modifications to the Suzuki reaction and mechanistic insights on the NBS mediated cleavage of benzylidene acetals /

One of the most challenging tasks for a synthetic organic chemist today, is the development of chemo, regio, and stereoselective methodologies toward the total synthesis of macromolecules. r . The objective of my thesis was to develop methodologies towards this end. The first part of my project was to develop highly functionalized chirons from D-glucose, a cheap, chiral starting material, to be utilized in this capacity. The second part of the project dealt with modifying the carbon-carbon bond forming Suzuki reaction, which is utilized quite often as a means of combining molecular sub units in total synthesis applications. As previously stated the first area of the project was to develop high value chirons from D-glucose, but the mechanism of their formation was also investigated. The free radical initiated oxidative fragmentation of benzylidene acetals was investigated through the use of several test-case substrates in order to unravel the possible mechanistic pathways. This was performed by reacting the different acetals with N-bromosuccinimide and benzoyl peroxide in chlorobenzene at 70^C in all cases. Of the three mechanistic pathways discussed in the literature, it was determined, from the various reaction products obtained, that the fragmentation of the initial benzylic radical does not occur spontaneously but rather, oxidation proceeds to give the benzyl bromide, which then fragments via a polar pathway. It was also discovered that the regioselectivity of the fragmentation step could be altered through incorporation of an allylic system into the benzylidene acetal. This allows for the acquisition of a new set of densely functionalized. chiral, valuable synthetic intermediates in only a few steps and in high yields from a-Dglucose. The second part of the project was the utilization of the phosphonium salt room temperature ionic liquid tetradecyltrihexylphosphonium chloride (THPC) as an efficient reusable medium for the palladium catalyzed Suzuki cross-coupling reaction of aryl halides, including aryl chlorides, under mild conditions. The cross-coupling reactions were found to proceed in THPC containing small amounts of water and toluene using potassium phosphate and 1% Pd2(dba)3. Variously substituted iodobenzenes, including electron rich derivatives, reacted efficiently in THPC with a variety of arylboronic acids and afforded complete conversion within 1 hour at 50 ^C. The corresponding aryl bromides also reacted under these conditions with the addition of a catalytic amount of triphenylphosphine that allowed for complete conversion and high isolated yields. The reactions involving aryl chlorides were considerably slower, although the addition of triphenylphosphine and heating at 70 ^C allowed high conversion of electron deficient derivatives. Addition of water and hexane to the reaction products results in a triphasic system in which the top hexane phase contained the biaryl products, the palladium catalyst remained fully dissolved in the central THPC layer, while the inorganic salts were extracted into the lower aqueous phase. The catalyst was then recycled by removing the top and bottom layers and adding the reagents to the ionic liquid which was heated again at 50 ^C; resulting in complete turnover of iodobenzene. Repetition of this procedure gave the biphenyl product in 82-97% yield (repeated five times) for both the initial and recycled reaction sequences.

(A) BODIPY as a versatile fluorophore (B) Synthesis of PNAs via Staudinger reaction

(A) In recent years, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores have attracted considerable interest due to their unique photochemical properties. However detailed studies on the stability of BODIPY and analogues under acidic and basic conditions have been lacking. Thus the stability of a series of BODIPY analogues in acidic (di- and trichloroacetic acid) and basic (aqueous ammonium hydroxide) conditions was investigated using 11B NMR spectroscopy. Among the analogues tested, 4,4-diphenyl BODIPY was the most stable under the conditions used in the experiments. It was found that reaction of 4,4-dimethoxy BODIPY with dichloroacetic acid gave mixed anhydride 4,4-bis(dichloroacetoxy) BODIPY in good yields. Treatment of the latter mixed anhydride with alcohols such as methanol and ethanol in the presence of a base afforded corresponding borate esters, whereas treatment with 1,2-diols such as ethylene glycol and catechol in the presence of a base gave corresponding cyclic borate esters. Furthermore treatment of 4,4-difluoro-8-methyl-BODIPY with secondary amines in dihalomethane resulted in carbon–carbon bond formation at the meso-methyl position of BODIPY via Mannich-type reactions. The resulting modified BODIPY fluorophores possess high fluorescent quantum yields. Five BODIPY analogues bearing potential ion-binding moieties were synthesized via this Mannich-type reaction. Among these, the BODIPY bearing an aza-18-crown-5 tether was found to be selective towards copper (II) ion, resulting in a large blue shift in absorption and sharp fluorescent quenching, whereas aza-15-crown-4 analogue was selected towards fluoride ion, leading to effective florescent quenching and blue shift. (B) Peptide nucleic acids (PNA), as mimics of natural nucleic acids, have been widely applied in molecular biology and biotechnology. Currently, the preparation of PNA oligomers is commonly achieved by a coupling reaction between carboxyl and amino groups in the presence of an activator. In this thesis attempts were made towards the synthesis of PNA through the Staudinger ligation reactions between C-terminal diphenylphosphinomethanethiol thioesters and N-terminal α-azido PNA building blocks.

Decarboxylative Generation of Carbenes for the Synthesis of N-Heterocyclic Carbene Copper(I) Complexes - Applications in the Oxidative Coupling of 2-Naphthols

Le présent mémoire décrit la synthèse et l’utilité de complexes Cu-NHC. En premier lieu, la synthèse de complexes de cuivre porteurs de ligand(s) de type carbène-N-hétérocyclique (NHC) via une génération décarboxylative de carbènes sera présentée. En effet, de précédents rapports font état de l’utilisation de carboxylates d’imidazol(in)ium en tant que précurseurs carbéniques sous conditions thermolytiques. Ainsi, la présente étude montre l’utilisation de ces espèces zwitterioniques pour la synthèse de complexes de cuivre(I) mono- et bis-NHC comportant divers substituants et contre-ions. Une seconde partie du projet se concentrera sur l’évaluation de complexes Cu-NHC en tant que catalyseurs pour la synthèse de 2,2’-binaphtols via une réaction de couplage oxydatif de naphtols. L’objectif de ce projet de recherche est d’étudier les effets de variations structurales de différents complexes Cu-NHC afin de construire un processus catalytique plus efficace. Les effets de la structure du catalyseur sur la réaction de couplage ont été évalués en variant son contre-ion, le nombre de ligands NHC se coordonnant au cuivre, ainsi que la nature des substituants du ligand.

Double coupling reactions of 3,4-bis(stannyl)furanone: facile preparation of diaryl- and dibenzylfuranones

The palladium-catalyzed cross-coupling reaction of 3,4-bis(tributylstannyl)furan-2(5H)-one using chelating ligand or polar solvent gives mixtures of single and double coupled products, even when one equivalent of halide coupling partner is used. After optimization, the double coupling reaction was shown to be general, with the use of two equivalents of aryl iodides giving 3,4-disubstituted furanones, The reaction using benzyl bromides proceeds at lower temperatures than the corresponding coupling using aryl iodides, giving dibenzylfuranones. The methodology has been exemplified in a synthesis of (+/-)-hinokinin.

Synthesis, structure, and electrochemical properties of a family of 2-(arylazo)phenolate complexes of ruthenium with unusual C-C coupling and N=Ncleavage

Reaction of 2-(4'-R-phenylazo)-4-methylphenols (R = OCH3, CH3, H, Cl, and NO2) with [Ru(dmso)(4)Cl-2] affords a family of five ruthenium(III) complexes, containing a 2-(arylazo)phenolate ligand forming a six-membered chelate ring and a tetradentate ligand formed from two 2-(arylazo) phenols via an unusual C-C coupling linki.ng the two ortho carbons of the phenyl rings in the arylazo fragment. A similar reaction with 2-(2'-methylphenylazo)-4-methylphenol with [Ru(dmso)(4)Cl-2] has afforded a similar complex, in which one 2-(2'-methylphenylazo)-4-methylphenolate ligand is coordinated forming a six-membered chelate ring, and the other two ligands have undergone the C-C coupling reaction, and the coupled species is coordinated as a tetradentate ligand forming a five-membered N,O-chelate ring, a nine-membered N,N-chelate ring, and another five-membered chelate ring. Reaction of 2-(2',6'-dimethylphenylazo)-4-methylphenol with [Ru(dmso)(4)Cl-2] has afforded a complex in which two 2-(2',6'-dimethylphenylazo)-4-methylphenols are coordinated as bidentate N,O-donors forming five- and six-membered chelate rings, while the third one has undergone cleavage across the N=N bond, and the phenolate fragment, thus generated, remains coordinated to the metal center in the iminosemiquinonate form. Structures of four selected complexes have been determined by X-ray crystallography. The first six complexes are one-electron paramagnetic and show rhombic ESR spectra. The last complex is diamagnetic and shows characteristic H-1 NMR signals. All the complexes show intense charge-transfer transitions in the visible region and a Ru(III)-Ru(IV) oxidation on the positive side of SCE and a Ru(III)-Ru(II) reduction on the negative side.

Solid-phase synthesis of an A-B loop mimetic of the C epsilon 3 domain of human IgE: macrocyclization by Sonogashira coupling

The solid-phase synthesis of a cyclic peptide containing the 21-residue epitope found in the A-B loop of the Cepsilon3 domain of human immunoglobulin E has been carried out. The key macrocyclization step to form the 65-membered ring is achieved in similar to15% yield via an "on-resin" Sonogashira coupling reaction which concomitantly installs a diphenylacetylene amino acid conformational constraint within the loop.

Palladium-coated nickel nanoclusters: new Hiyama cross-coupling catalysts

The advantages of bimetallic nanoparticles as C - C coupling catalysts are discussed, and a simple, bottom- up synthesis method of core - shell Ni - Pd clusters is presented. This method combines electrochemical and 'wet chemical' techniques, and enables the preparation of highly monodispersed structured bimetallic nanoclusters. The double- anode electrochemical cell is described in detail. The core - shell Ni - Pd clusters were then applied as catalysts in the Hiyama cross- coupling reaction between phenyltrimethoxysilane and various haloaryls. Good product yields were obtained with a variety of iodo- and bromoaryls. We found that, for a fixed amount of Pd atoms, the core - shell clusters outperform both the monometallic Pd clusters and the alloy bimetallic Ni - Pd ones. THF is an excellent solvent for this process, with less than 2% homocoupling by-product. The roles of the stabiliser and the solvent are discussed.

A single-step procedure for the preparation of palladium nanoparticles and a phosphine-functionalized support as catalyst for Suzuki cross-coupling reactions

We here report the preparation of supported palladium nanoparticles (NPs) stabilized by pendant phosphine groups by reacting a palladium complex containing the ligand 2-(diphenylphosphino)benzaldehyde with an amino-functionalized silica surface The Pd nanocatalyst is active for Suzuki cross-coupling reaction avoiding any addition of other sources of phosphine ligands The Pd intermediates and Pd NPs were characterized by solid-state nuclear magnetic resonance and transmission electron microscopy techniques The synthetic method was also applied to prepare magnetically recoverable Pd NPs leading to a catalyst that could be reused for up to 10 recycles In summary we gathered the advantages of heterogeneous catalysis magnetic separation and enhanced catalytic activity of palladium promoted by phosphine ligands to synthesize a new catalyst for Suzuki cross-coupling reactions The Pd NP catalyst prepared on the phosphine-functionalized support was more active and selective than a similar Pd NP catalyst prepared on an amino-functionalized support (C) 2010 Elsevier Inc All rights reserved

Synthesis of alpha,beta-unsaturated aryl esters via Heck reaction of unsymmetrical aryl tellurides

A variety of alpha,beta-unsaturated aryl esters were prepared by the direct reaction of unsymmetrical aryltellurides and ethyl acrylate, catalyzed by PdCl(2) via a Heck cross-coupling reaction. (C) 2009 Elsevier Ltd. All rights reserved.

Novel cross-coupling reactions between organotellurides and Grignard reagents employing a MnCl2/CuI catalytic system

We present a general protocol for the cross-coupling reaction of Grignard reagents and organic tellurides. Aryl Grignard reagents react stereospecifically with vinyl tellurides in the presence of a catalytic amount of manganese (II) chloride and copper (I) iodide to produce good yields of the corresponding cross-coupling products. (C) 2012 Published by Elsevier Ltd.

Dimerization of Poly(methyl methacrylate) Chains Using Radical Trap-Assisted Atom Transfer Radical Coupling

End-brominated poly(methyl methacrylate) (PMMABr) was prepared by atom transfer radical polymerization (ATRP) and employed in a series of atom transfer radical coupling (ATRC) and radical trap-assisted ATRC (RTA-ATRG) reactions. When coupling reactions were performed in the absence of a nitroso radical trap-traditional ATRC condition-very little coupling of the PMMA chains was observed, consistent with disproportionation as the major termination pathway for two PMMA chain-end radicals in our reactions. When 2-methyl-2-nitrosopropane (MNP) was used as the radical trap, coupling of the PMMA chains in this attempted RTA-ATRC reaction was again unsuccessful, owing to capping of the PMMA chains with a bulky nitroxide and preventing further coupling. Analogous reactions performed using nitrosobenzene (NBz) as the radical trap showed significant dimerization, as observed by gel permeation chromatography (GPC) by a shift in the apparent molecular weight compared to the PMMABr precursors. The extent of coupling was found to depend on the concentrion of NBz compared to the PMMABr chain ends, as well as the temperature and time of the coupling reaction. To a lesser extent, the concentrations of copper(I) bromide (CuBr), nitrogen ligand (N,N,N',N',N"-pentamethyldiethylenetriamine = PMDETA), and elemental copper (Cu) were also found to play a role in the success of the RTA-ATRC reaction. The highest levels of dimerization were observed when the coupling reaction was carried out at 80 degrees C for 0.5h, with ratio of 1:4:2.5:8:1 equiv of NBz: CuBr:Cu:PMDETA:PMMABr.