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Synthesis and catalytic application of palladium imidazol(in)ium-2- dithiocarboxylate complexes

The palladium(ii) dimer, [Pd(C,N-C6H4CH 2NMe2)Cl]2 reacts with two equivalents of the NHC¡¤CS2 zwitterionic ligands [NHC = IPr (1,3- diisopropylimidazol-2-ylidene), ICy (1,3-dicyclohexylimidazol-2-ylidene), IMes (1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene), IDip (1,3-bis(2,6- diisopropylphenyl)imidazol-2-ylidene), SIMes (1,3-bis(2,4,6-trimethylphenyl) imidazolin-2-ylidene)] in the presence of NH4PF6, to yield the cationic products [Pd(C,N-C6H4CH2NMe 2)(S2C¡¤NHC)]+. In a similar fashion, the compounds [Pd(C,N-bzq)(S2C¡¤NHC)]+ (bzq = benzo[h]quinolinyl, NHC = ICy, IMes, IDip) are obtained from the corresponding dimer [Pd(C,N-bzq)Cl]2. The bis(phosphine) compounds [Pd(S 2C¡¤NHC)(PPh3)2]2+ (NHC = ICy, IMes, IDip, SIMes) are obtained on treatment of [PdCl2(PPh 3)2] with NHC¡¤CS2 zwitterions in the presence of NH4PF6. The reaction of [PdCl 2(dppf)] with IMes¡¤CS2 and NH4PF 6 provides the complex [Pd(S2C¡¤IMes)(dppf)] 2+. The complexes [Pd(S2C¡¤NHC)(PPh 3)2](PF6)2 (NHC = IMes, IDip) were active pre-catalysts (1 mol% loading) for the conversion of benzo[h]quinoline to 10-methoxybenzo[h]quinoline in the presence of PhI(OAc)2 and methanol. The intermediacy of [Pd(C,N-bzq)(S2C¡¤NHC)] + was supported by the high yield of 10-methoxybenzo[h]quinoline using [Pd(C,N-bzq)(S2C¡¤IDip)]+ to promote the same reaction. Small amounts of 2,10-dimethoxybenzo[h]quinoline were also isolated from these reactions. Using [Pd(C,N-bzq)(S2C¡¤IDip)] + and N-chlorosuccinimide as the oxidant led to the formation of 10-chlorobenzo[h]quinoline in moderate yield from benzo[h]quinoline. The molecular structures of [Pd(S2C¡¤IMes)(PPh3) 2](PF6)2 and [Pd(S2C¡¤IMes) (dppf)](PF6)2 were determined crystallographically.

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

Top Picks: new discover of Dichlorobis(tri-o-tolylphosphine)palladium(II)

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Phosphapalladacycle-catalyzed heck reactions for efficient synthesis of trisubstituted olefins: Evidence for palladium(0) intermediates

The coupling reaction of 1,1-disubstituted olefins (alpha-methyl-styrene, n-butyl methacrylate) with various aryl bromides (Heck reaction) has been studied as a new concept to synthesize trisubstituted olefins. Surprisingly, the nature of the base dramatically influences the product distribution. Thus, a systematic investigation on the role of base in Heck reactions of 1,1-disubstituted olefins was performed. Less coordinating bases like NaOAc, NaOBz or Na2CO3 yield a statistical distribution of regioisomers with the terminal olefin 10 as the major product. However, by using amines like Bu3N or diisopropylethylamine (DIPEA) as base internal olefins can be synthesized with high selectivities. With phosphapalladacycle 3 as catalyst precursor, we were able to obtain catalyst turnover numbers up to 1000, while Pd(OAc)2/2PPh3 was one order of magnitude less active. Analysis of the reaction profile by kinetic investigations led to the postulation of a reduction and subsequent oxidative addition of the catalyst precursor 3 to form 12 as catalytically active intermediate.

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

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Palladium-Catalyzed Cross-Coupling Reaction of Alkyltrifluorosilanes with Aryl Halides

A cross-coupling reaction of alkyltrifluorosilanes with aryl halides was achieved using a catalytic amount of tetrakis-(triphenylphosphine)palladium(0) and excess of tetrabutylammonium fluoride (TBAF) at 100C with high chemoselectitvity. Functional groups like nitro, ketone carbonyl, and formyl tolerated the coupling conditions. Because potassium(18-crown-6) alkyltetrafluorosilicates also underwent a cross-coupling reaction in the presence of an additional molar amount of TBAF, the active species of the coupling reaction was assumed to be pentacoordinate silicates. TBAF in excess was considered to be required for trapping the tetrafluorosilane produced in the catalytic cycle of the cross-coupling reaction.

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

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TiO2 Nanoparticles Catalyzed Chemoselective Synthesis of 2-Chloroquinolinyl-4-quinolinones and their Intramolecular Cyclization through Palladium Catalyzed Sonogashira Coupling Reaction

Abstract: The 2-chloro-3-formyl quinolines 1, were chemoselectivity and effectively converted into their corresponding 2-chloroquinolinyl-4-quinolinones 3 through Knoevenagel condensation/aza-Michael addition utilizing TiO2 nanoparticles. The Sonogashira coupling of 2-chloroquinolinyl moiety of the quinolinone, 3 gave unprecedented cyclised products 1,6-naphthyridines, 5 through cascade reaction in good yields and purity. Graphical Abstract: [Figure not available: see fulltext.]

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

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Nonsymmetrical 3,4-dithienylmaleimides by cross-coupling reactions with indium organometallics: Synthesis and photochemical studies

The synthesis and photochemical study of novel nonsymmetrical 1,2-dithienylethenes (DTEs) with a maleimide bridge have been carried out. The synthetic approach to the DTEs was based on successive selective palladium-catalyzed cross-coupling reactions of 5-susbtituted-2-methyl-3-thiophenyl indium reagents with 3,4-dichloromaleimides. The required organoindium reagents were prepared from 2-methyl-3,5-dibromothiophene by a selective (C-5) coupling reaction with triorganoindium compounds (R3In) and subsequent metal-halogen exchange. The coupling reactions usually gave good yields and have a high atom economy with substoichiometric amounts of R3In. The results of photochemical studies show that these novel dithienylmaleimides undergo a photocyclization reaction upon irradiation in the UV region and a photocycloreversion after excitation in the visible region, thus they can be used as photochemical switches. ON-OFF operations can be repeated in successive cycles without appreciable loss of effectiveness in the process.

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

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Concise synthesis of prenylated and geranylated chalcone natural products by regiospecific iodination and Suzuki coupling reactions

Four natural chalcones bearing prenyl or geranyl groups, i.e., isobavachalcone (1), bavachalcone (2), xanthoangelol (3), and 2?,4?,4-trihydroxy-5?-geranylchalcone (isoxanthoangelol, 4) were synthesized by using a regio-selective iodination and the Suzuki coupling reaction as key steps. Among them, the first total synthesis of 2?,4?,4-trihydroxy-5?-geranylchalcone was achieved in 36% overall yield. Comparing with the reported methods based on C-alkylation or O-alkylation followed by Claisen rearrangement to introduce the side chain, this new strategy capitalizes on a precious regiochemical control during iodination. The overall yields for the synthesis of the first three chalcones were improved from 17% to 53%, 12% to 35%, and 28% to 50%, respectively.

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

Awesome and Easy Science Experiments about [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)

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Kumada – Corriu coupling of Grignard reagents, probed with a chiral Grignard reagent

The Grignard reagent 2, in which the magnesium-bearing carbon atom is the sole stereogenic centre has been coupled with vinyl bromide under Pd(0) or Ni(0)-catalysis to give compound 3 with full retention of configuration. Coupling using Fe(acac)3 or Co(acac)2 as catalyst was accompanied by considerable racemisation. These findings are discussed with respect to a dichotomy between concerted polar and stepwise SET transmetallation pathways.

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

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(S)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530), a Potent, Orally Bioavailable, and Brain-Penetrable Dual Inhibitor of Class i PI3K and mTOR Kinase

The phosphoinositide 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) pathway is frequently overactivated in cancer, and drives cell growth, proliferation, survival, and metastasis. Here, we report a structure-activity relationship study, which led to the discovery of a drug-like adenosine 5?-triphosphate-site PI3K/mTOR kinase inhibitor: (S)-4-(difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530, compound 6), which qualifies as a clinical candidate due to its potency and specificity for PI3K and mTOR kinases, and its pharmacokinetic properties, including brain penetration. Compound 6 showed excellent selectivity over a wide panel of kinases and an excellent selectivity against unrelated receptor enzymes and ion channels. Moreover, compound 6 prevented cell growth in a cancer cell line panel. The preclinical in vivo characterization of compound 6 in an OVCAR-3 xenograft model demonstrated good oral bioavailability, excellent brain penetration, and efficacy. Initial toxicity studies in rats and dogs qualify 6 for further development as a therapeutic agent in oncology.

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

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A pseudo-rotaxane based on an iridium(III)-copper(I) dyad

The synthesis of a pseudo-rotaxane containing two metal centres has been achieved using the coordination of a ditopic organic ligand on an iridium(III) complex followed by the coordination of a copper(I) centre. Preliminary photophysical studies indicate that the excited state of the iridium is quenched by the copper unit.

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

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Synthesis, structural characterization, and unusual field-effect behavior of organic transistor semiconductor oligomers: Inferiority of oxadiazole compared with other electron-withdrawing subunits

A new series of heterocyclic oligomers based on the 1,3,4-oxadiazole ring were synthesized. Other electron-deficient cores (fluorenone and fumaronitrile) were introduced to investigate the oligomers as n-channel materials. The physical properties, thin film morphologies, and field-effecttransistor characteristics of the oligomers were evaluated. Thin films were deposited at different substrate temperatures and on variously coat ed Si/Si02 for device optimization. Contrary to our expectations, the thin film devices of 4 revealed p-channel behavior, and the average hole mobility was 0.14 cm 2 V-1 s-1 (maximum value 0.18 cm2 V-1 s-1). Compound 11 is the first example of an oxadiazole-containing organic semiconductor (OSC) oligomer in an n-channel organic field-effect transistor (OFET) and shows moderate mobilities. Non- oxadiazole-containing oligomers 9 and 12 showed n-channel OFET behavior on hexamethyldisilazane- treated and Cytop spin-coated Si02 in vacuum. These are the first fluorenone- and fumaronitrile-based n-OSCs demonstrated in transistors. However, oxadiazole-core materials 14 and 16 were inactive in transistordevices.

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