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The synthesis of zinc (2-diethoxyphosphorylethynyl)porphyrins and their self-organization in solid state and in solution are reported. Copper-cocatalyzed Sonogashira reaction involving bromoporphyrins and diethyl ethynylphosphonate was used to prepare meso-substituted derivatives Zn4 and Zn5 bearing one or two ethynylphosphonate substituents at the macrocycle. In contrast, copper-free Sonogashira coupling of 2-bromoporphyrin with diethyl ethynylphosphonate is more convenient to prepare porphyrin Zn6 bearing this substituent at the beta-pyrrolic position of the macrocycle. The structures of complexes Zn4a·C7H8, Zn4a·CHCl3, Zn4c and Zn5b·CH2Cl2 in crystals were elucidated by X-ray diffraction analysis. The supramolecular self-assembly through weak coordinative binding of the phosphoryl group of one porphyrin molecule to the zinc(II) ion located in the center of another macrocyclic cavity is observed in all crystals. However, ZnII-porphyrinates Zn4a and Zn5b exist in the solid state as mutually coordinated dimers while complex Zn4c displays a 1D polymer structure. In all dimer complexes, neighboring porphyrin rings are spatially separated, with Zn?O and P=O bond lengths being similar, while the interplanar porphyrin distance is variable, depending on weak intermolecular interactions in the crystals. The self-organization of (phosphorylethynyl)porphyrins is also observed in weakly polar chloroform and detectable by NMR and UV/Vis spectroscopy. The mutually coordinated dimer of electron-deficient porphyrin Zn5b was observed in 5 × 10?3 m chloroform solution even at room temperature. The kinetic lability of this supramolecular complex was proven by NMR spectroscopy. The associates of more electron-donating porphyrins Zn4a and Zn4c are less stable, and self-assembled dimers become the predominant species in 5 × 10?3 m chloroform solution only below 225 K. The self-assembly of porphyrin Zn4a and Zn5b in more diluted solutions (up to 10?6 m) was also investigated by UV/Vis spectroscopy.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Methods for the synthesis of dihydroazaphenanthrene fused to macrocycles (2) and medium-ring heterocycles (4), as well as 1,4-benzodiazepine-2,5-diones (5), are developed. A distinctly different catalytic property of palladium and copper catalysts was uncovered that leads to the development of a divergent synthesis of two different heterocyclic scaffolds from the same starting materials, simply by metal-switching. Thus, starting from linear amide 3, palladium acetate triggers a domino intramolecular N-arylation/ C-H activation/aryl-aryl bond-forming process to provide 4, while copper iodide promotes only the intramolecular N-arylation reaction leading to 5. In combination with the Ugi multicomponent reaction (Ugi-4CR) for the preparation of the linear amides, a two-step synthesis of either the 5,6-dihydro-8H-5,7a- diazacyclohepta[jk]phenanthrene-4,7-dione (4) or 1,4-benzodiazepine-2,5-diones (5), by appropriate choice of metal catalyst, is subsequently developed from very simple starting materials.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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An efficient one-pot, two-step procedure has been successfully applied for the synthesis of a series of 2-(5-phenylindol-3-yl)benzimidazoles. The first step was cyclocondensation-oxidation of 5-bromoindole-3-aldehydes with o-phenylenediamines in 1,4-dioxane, which was promoted by activated carbon and used atmospheric air as a “green” oxidant. The resulting 2-(5-bromoindol-3-yl)benzimidazoles in the pot were in situ coupled with postadded phenylboronic acids, and catalyzed with PdCl2(dppf) in 1,4-dioxane-H2O to afford the desired compounds with satisfactorily high yields. The relationship between the synthesized compounds’ absorption, and fluorescence spectra with molecular structures has been investigated with experimental data and theoretical calculations.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Compounds of formula (I) described herein are useful for inhibiting phosphoinositide 3-kinases (PI3K) and the treatment of disorders associated with PI3K enzymes.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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An improved synthesis of 4,4-bis(hydroxymethyl)-1,2-diselenolane and the complexation properties of the corresponding diselenolato dianion to group-10 metals are reported. We describe an efficient and straightforward procedure that bypasses the isolation of the malodorous and airsensitive diselenol and starts with the diselenide appropriate group-10 metal complex bearing phosphane and chlorido ligands. A series of complexes with various monoand bidentate phosphanes is prepared and characterised by multinuclear NMR spectroscopy, mass spectrometry, and elemental analysis. Furthermore, the structure of most complexes is studied by single-crystal X-ray diffraction to establish their supramolecular arrangement in the solid state. Consequently, several group-10 metal complexes with P-M-P angles (bite angles) in the range from 71-108 are investigated. The use of the sterically demanding bridging phosphane 4,5-bis(diphenylphosphanyl)-9,9-dimethylxanthene, which exhibits a large bite angle yields a mixture of a di- and trinuclear complex. While the platinum-containing complexes are proven to be rather stable, the palladium and nickel analogues tend to decompose. Especially, the nickel complexes were found to be sensitive against: oxidation. This circumstance leads to the formation of the so far unknown 1,8-bis(diphenylphosphanyl)naphthalene monooxide, the formation and structure of which could be confirmed from NMR spectroscopic data and single-crystal X-ray diffraction.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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We present the design, synthesis, and biological applications of mitochondria peroxy yellow 1 (MitoPY1), a new type of bifunctional fluorescent probe for imaging hydrogen peroxide levels within the mitochondria of living cells. MitoPY1 combines a chemoselective boronate-based switch and a mitochondrial-targeting phosphonium moiety for detection of hydrogen peroxide localized to cellular mitochondria. Confocal microscopy and flow cytometry experiments in a variety of mammalian cell types show that MitoPY1 can visualize localized changes in mitochondrial hydrogen peroxide concentrations generated by situations of oxidative stress. Copyright

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The organometallic tetraradical 1,2,4,5-[(eta7-C 7H7)V(eta5-C5H4)] 4C6H2 has been prepared and structurally characterized. The isotropic EPR spectrum displays 29 a(51V) hyperfine lines, the intensity distribution slightly deviating from binomial. Exchange coupling therefore approaches the strong exchange limit, J ortho ? Jmeta ? Jpara, ?50 a( 51V) with a(51V) = 0.0067 cm-1. According to magnetic susceptometry, the interaction is antiferromagnetic. While redox splittings deltaE1/2, are resolved for the four reduction steps this is not the case for oxidation. The Royal Society of Chemistry 2005.

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Chapter 1 An introduction to palladium catalysis,
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Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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In the presence of a Pd(ii)/P-ligand catalytic system, decarboxylative alkynylation of alkynyl carboxylic acids and arylsulfonyl hydrazides by desulfinative coupling could provide aryl alkynes in satisfactory yields by either judiciously selecting palladium catalysts or modulating phosphine ligands under mild conditions. The reported coupling reactions are very practical as they do not require the protection of inert gas or oxygen and are tolerant to many functional groups.

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Palladium/carbon catalyst regeneration and mechanical application method

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A versatile synthetic route to new 4-quinolone-based polycyclic systems is described. TFA-catalyzed intramolecular reaction of N-unsubstituted quinolone-2-carboxylic acid amides gives structurally diverse compounds, depending on the length of the chain. Acid treatment of beta-oxoamides furnishes 3H-pyrazino[1,2-a]quinoline-4,6-diones, due to the nucleophilic attack of N-1 to the carbonyl group, whereas TFA treatment of delta- and epsilon-oxoamides leads to the formation of tetracyclic compounds by a tandem heteroannulation reaction.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method