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This paper presents effects of varying bidentate phosphine steric properties, electronic properties, and bite angle on product ratios in the amination of aryl bromides. Comparison of the ratios of amine products to dehydrohalogenation products showed that catalysts containing electron rich, modestly hindered phosphines with small bite angles (~-90) gave the best selectivities. Surprisingly, the arene side product formed from reaction of alkylamines deuterated in the N-H position or deuterated in the position alpha to the nitrogen showed low levels of deuterium incorporation in many examples. Steric properties and ligand bite angle had the greatest impact on the selectivity for monoarylation versus diarylation of primary amines; ligands with small bite angles gave higher monoarylation-to-diarylation ratios, as did ligands with increased steric bulk. Electron poor or sterically hindered bidentate phosphines reduced the amount of product resulting from aryl exchange of electron rich palladium-bound arenes with those of aryl groups on the phosphine ligands.

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

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Building on our previous discovery and reactivity explorations of the Pd(I) dimer [(PtBu3)PdBr]2-mediated halogen exchange of aryl iodides [ Chem. Sci. 2013, 4, 4434 ], this report presents kinetic studies of this process, giving first-order kinetic dependence in the Pd(I) dimer and aryl iodide. An activation free energy barrier of DeltaG? = 24.9 ± 3.3 kcal/mol was experimentally determined. Extensive computational studies on the likely reaction pathway were subsequently carried out. A variety of DFT methods were assessed, ranging from dispersion-free methods to those that better account for dispersion (M06L, omegaB97XD, D3-DFT). While significant discrepancies in the quantitative prediction of activation barriers were observed, all computational methods consistently predicted the analogous qualitative reactivity that is in agreement with all spectroscopic and reactivity data collected. Overall, these data provide compelling additional support of the direct reactivity of Pd(I)-Pd(I) with aryl iodides.

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

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Out of the blue: The marine macrolide spirastrellolide A is a potent and selective inhibitor of protein phosphatase 2A and a lead for anticancer therapies. A flexible and modular synthetic strategy has been developed with two routes for the construction of the DEF bis-spiroacetal subunit. The optimized Suzuki coupling approach results in the efficient preparation of a C17-C40 aldehyde that forms the cornerstone of the first total synthesis. (Chemical Equation Presented).

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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 novel strategy for direct aryl hydroxylation via Pd-catalysed Csp2-H activation through an unprecedented hydroxyl radical transfer from 1,4-dioxane, used as a solvent, is reported with bio relevant and sterically hindered heterocycles and various acyclic functionalities as versatile directing groups.

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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 synthesis of the new bis[2-(diphenylphosphino)ethyl](hydroxymethyl)phosphine tridentate ligand LCH2OH/Ph is reported. The ligand reacts with [Pd(Cl)2(PhCN)2] to form [Pd(LCH2OH/Ph)Cl]Cl. Exchange of the chloride ions for triflate (OTf-) using AgOTf yielded pure [Pd(LCH2OH/Ph)OTf]OTf. In addition to spectral characterization, the free ligand, LCH2OH/Ph, and the PdII complex, [Pd(LCH2OH/Ph)OTf]OTf, were structurally characterized. The synthesis of the Triphos ligand derivative LCH2OH/Ph is reported, along with the corresponding PdII complex. In addition to spectral characterization of the free ligand and PdII complex, structural characterization is reported for [Pd(LCH2OH/Ph)OTf]OTf.

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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 application of borylated N-aryl sulfoximines as newly designed synthetic building blocks in Suzuki-type cross coupling reactions offers rapid access to a wide range of N-biaryl derivatives with potential relevance for medicinal chemistry and crop protection in good to excellent yields (up to 98%). (Figure presented.).

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

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Although carbonylation of aryl halides is widely applied in synthesis, heterogeneous catalysts for this transformation are scarce. In order to heterogeneously catalyze the amidocarbonylation of bromoarenes, a polymer-supported catalytic system was assembled from Pd(dba)2 and a polymer-bound diphosphine chelate, prepared via solid-phase synthesis from serinol. The system efficiently converts aryl bromides into carboxamides in a reaction with CO and aliphatic or aromatic amines. Comparison with other supported phosphine ligands demonstrated the superiority of the chelate diphosphine structure. Remarkably, partial complexation of the polymer-tethered ligating sites with Pd forms notably better catalytic systems than the full complexation. The reactivity pattern of the catalytic system points to the oxidative addition as the rate-determining step of the catalytic cycle.

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

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To investigate the effect of the fluoride phenyl side-chains into quinoxaline (PQx) unit on the photovoltaic performances of polymers, we demonstrated the synthesis and characterization of two novel wide-bandgap (WBG) copolymers, PIDT-DTPQx and PIDT-DTFPQx, in which indacenodithiophene (IDT), 2,3-diphenylquinoxaline (PQx) (and/or 2,3-bis(4-fluorophenyl)quinoxaline (FPQx)) and thiophene (T) were used as the donor (D) unit, acceptor (A) unit and pi-bridge, respectively. Compared to the non-fluorine substituted PIDT-DTPQx, fluorine substituted PIDT-DTFPQx presents a deep HOMO energy level and a high hole mobility. Obviously, improved the Voc, Jsc, and FF simultaneously, giving rise to overall efficiencies in the PIDT-DTFPQx/PC71BM-based PSCs. A highest PCE of 5.78% was obtained with a Voc of 0.86 V, Jsc of 10.84 mA cm-2 and FF of 61.7% in the PIDT-DTFPQx/PC71BM-based PSCs, while PIDT-DTPQx based devices also demonstrated a PCE of 5.11%, under the illumination of AM 1.5G (100 mW cm-2). Note that these PCE values were achieved for PSCs without any extra treatments. Furthermore, these optimal devices have a film thickness of about 175 nm for the polymer/PC71BM-based active layers. The results provide that introduction of the fluorine atom into quinoxaline unit by side-chain engineering is one of the effective strategies to construct the promising polymer donor materials for future application of large-area polymer solar cells.

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

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Disclosed are compounds of Formula 1, or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, and R4 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating Type I hypersensitivity reactions, autoimmune diseases, inflammatory disorders, cancer, non-malignant proliferative disorders, and other conditions associated with BTK.

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

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Palladacycles derived from l-tyrosine methyl ester, (S)-[Pd 2{C,N-C6H3CH2CH(CO 2Me)NH2-2,(OH)-4}2(mu-Br)2] (1a-Br), and homoveratrylamine, [Pd2{C,N-C6H 2CH2CH2NH2-6,(OMe) 2-3,4}2(mu-Br)2] (1b-Br), can be easily prepared in good yield by reacting Pd(OAc)2, the corresponding ammonium triflate, and NaBr. Under the same conditions, the reaction of Pd(OAc)2 with the free amine affords a low yield of the corresponding acetato complex 1a-OAc or 1b-OAc (the latter only detected in solution). In our hands, the previously reported palladation at the C2 position of homoveratrylamine with Pd(OAc)2 is not observed. Instead, a complex mixture is obtained, mainly containing [Pd(OAc)2{NH 2CH2CH2C6H3(OMe) 2-3,4}2] and minor amounts of 1b-OAc, which reacts with NaBr to afford a new mixture from which [PdBr2{NH2CH 2CH2C6H3(OMe)2-3,4} 2] can be isolated and characterized. These and other adducts can be isolated from Pd(OAc)2, homoveratrylamine, and various ligands (PPh3 and Br-). 6-Bromohomoveratrylamine reacts with Pd(dba)2 in the presence of tmeda to give the complex [Pd{C,N-C 6H2CH2CH2NH2-6,(OMe) 2-3,4}(tmeda)]Br. Reactions of complexes 1 with acetylacetonato or neutral (PR3) ligands give products resulting from substitution or bridge-splitting reactions. While 1a-Br reacts with XyNC (1:2 molar ratio) to give (S)-[Pd{C,N-C6H3CH2CH(CO 2Me)NH2-2,(OH)-4}Br(CNXy)], 1b-Br gives [Pd{C,N-C(=NXy)-C6H2CH2CH2NH 2-6,(OMe)2-3,4}Br(CNXy)]. (S)-7-Hydroxy-3- (methoxycarbonyl)-3,4-dihydroisoquinolin-1(2H)-one and 6,7-dimethoxy-3,4- dihydroisoquinolin-1(2H)-one (corydaldine) have been synthesized through the stoichiometric carbonylation of palladacycles 1a-Br and 1b-Br. The crystal structures of a solvento intermediate in the ortho-metalation reaction of the triflate derivative of l-tyrosine methyl ester and four other complexes have been determined by X-ray diffraction studies.

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