Extracurricular laboratory:new discovery of 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex

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Disubstituted pyridine/pyrimidine ferrocenyl complexes have been obtained by mechanically induced Sukuzi coupling reactions in the solid state. It is shown that the solventless process is much faster, and more selective, than the same reaction carried out in solution. The synthesis and structure of the complex [Fe(eta5-C5H4-4-C5H 4N)(eta5-C5H4-3-C 4H3N2)] are reported as a test case.

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

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Trifluoroethylation: Aryl boronic acids can be catalytically trifluoroethylated with the readily available reagent CF3CH 2I (see scheme, dba=dibenzylideneacetone). The reaction tolerates a variety of functional groups and can be extended to the trifluoroethylation of aryl or alkenyl boronic esters. The method is also suitable for the late-stage installation of the CF3CH2 group into target molecules. Copyright

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

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The present invention relates to a compound represented by formula (I) and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing diabetes, hyperlipidemia, obesity, NASH, inflammation related disorders, and related diseases and conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR120. Pharmaceutical compositions and methods of treatment are also included.

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

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A new heterometallic dyad composed of a zinc porphyrin linked by bisethynyl quaterthiophene to a gold porphyrin was synthesized according to a stepwise modular approach. The latter dyad and the parent reference compounds (porphyrin-ethynylquaterthiophene) were characterized by electrochemistry, spectroelectrochemistry, and femtosecond transient absorption spectrocopy. We showed that light excitation of the zinc or the gold porphyrin induces a very fast and quantitative charge separation over a distance of 25 A which occurs through a superexchange mechanism. The lifetime of the charge-separated state is 3.3 ns in toluene and 100 ps in dichloromethane, and it recombines to the ground state in both solvents.

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

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(Chemical Equation Presented) We describe a concise synthesis of the structurally novel fungal extremophile metabolite berkelic acid, an effort leading to an unambiguous assignment of C22 stereochemistry. Our synthetic approach was inspired by the recognition that berkelic acid displays structural characteristics reminiscent of two other fungal metabolites, spicifernin and pulvilloric acid. Based on this notion, we executed a synthesis that features a Ag-catalyzed cascade dearomatization-cycloisomerization-cycloaddition sequence to couple two natural product inspired fragments. Notably, a spicifernin-like synthon was prepared with defined C22 stereochemistry in seven steps and three purifications (24-28% overall yield). A potentially useful anti-selective conjugate propargylation reaction was developed to introduce the vicinal stereodiad. An enantioconvergent synthesis of the other coupling partner, the aromatic precursor to pulvilloric acid methyl ester, was achieved in eight steps and 48% overall yield. The total synthesis of berkelic acid and its C22 epimer was thus completed in a 10 step linear sequence and 11-27% overall yield.

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

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The present application relates to novel substituted fused pyrimidines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.

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

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Selective iodination of the cyclopentadienylruthenium tricarbadecaboranyl complexes 1-(eta5-C5H5)-2-Ph-closo-1,2,3,4- RuC3B7H9 (1) and 1-(eta5-C 5(CH3)5)-2-Ph-closo-1,2,3,4-RuC 3B7H8 (2) to form their mono-iodo derivatives, 1-(eta5-C5H5)-2-Ph-6-I-closo-1,2,3,4-RuC 3B7H9 (3) and 1-(eta5-C 5(CH3)5)-2-Ph-6-I-closo-1,2,3,4-RuC 3B7H8 (4), was achieved in 90% yields by their reactions with ICl in CH2Cl2 solutions. Also isolated in trace amounts from the reaction with 2 was the di-iodo 1-(eta5- C5(CH3)5)-2-Ph-6,11-I2-closo-1,2,3, 4-RuC3B7H7, (5) complex. The sonication-promoted Sonogashira coupling reaction of 3 with terminal acetylenes catalyzed by Pd(dppf)Cl2/CuI yielded the functionalized ruthenatricarbadecaboranyl complexes 1-(eta5-C5H 5)-2-Ph-6-(Ph-C?C)-closo-1,2,3,4-RuC3B 7H8 (6), 1-(eta5-C5H 5)-2-Ph-6-[CH3CH2C(O)OCH2-C?C] -closo-1,2,3,4-RuC3B7H8 (7), 1-(eta5-C5H5)-2-Ph-6-[(eta5- C5H5)Fe(eta5-C5H 4)-C?C]-closo-1,2,3,4-RuC3B7H 8 (8) and 1-(eta5-C5H5)-2-Ph-6- [(CH3)3Si-C?C]-closo-1,2,3,4-RuC3B 7H8 (9). These reactions thus provide a versatile, systematic pathway for the syntheses of a wide variety of new types of functionalized ruthenatricarbadecaboranyl complexes.

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

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Ongoing interest in the discovery of selective JAK3 inhibitors led us to design novel covalent inhibitors that engage the JAK3 residue Cys909 by cyanamide, a structurally and mechanistically differentiated electrophile from other cysteine reacting groups previously incorporated in JAK3 covalent inhibitors. Through crystallography, kinetic, and computational studies, interaction of cyanamide 12 with Cys909 was optimized leading to potent and selective JAK3 inhibitors as exemplified by 32. In relevant cell-based assays and in agreement with previous results from this group, 32 demonstrated that selective inhibition of JAK3 is sufficient to drive JAK1/JAK3-mediated cellular responses. The contribution from extrahepatic processes to the clearance of cyanamide-based covalent inhibitors was also characterized using metabolic and pharmacokinetic data for 12. This work also gave key insights into a productive approach to decrease glutathione/glutathione S-transferase-mediated clearance, a challenge typically encountered during the discovery of covalent kinase inhibitors.

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

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The syntheses and characterization of series of new metallocene-bridged diphosphines and the structures of complexes of some of them with Pd(II) are reported. These complexes were examined as the catalysts in amination reactions of halogenoarenes and in the Suzuki reaction. The complexes based on ruthenocene (2) and osmocene (3) showed lower activities then the palladium complex with dppf in amination reactions and the same activities in the Suzuki reaction. New palladium complexes with the bidentate bulky and electron-rich ligands Fe(eta5-C5H4P(o-PriC 6H4)2)2 (6) and Feeta5- C5H4P(o-MeOC6H4)2) 2 (5) showed a very high catalytic activity in amination and Suzuki coupling of aryl bromides. A complex with ligand 6 was used in the amination of 4-bromotoluene by primary and secondary amines and showed excellent activity.

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

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A straightforward and atom-economical base-free palladium-catalyzed regioselective direct arylation of coumarins and chromenones is devised. This protocol is compatible with a wide variety of electron-donating and -withdrawing substituents and allows construction of various biologically important flavone and neoflavone backbones.

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