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Ethylamido fluorenes and improved method of making same

Novel substituted fluorene compunds of Formula I are active as melatonergic agents: STR1 wherein: X=H, halogen, OH or OZ;Z=C 1-6 alkyl; –(CH 2) m –CF 3 (m=0-2); CD 3 ; or STR2 n=1 or 2; and R=C 1-6 alkyl, C 3-6 cycloalkyl, C 2-4 alkenyl, halogen substituted C 1-6 alkyl, or C 1-6 alkoxy substituted C 1-6 alkyl.

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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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P-Chiral Phosphines Enabled by Palladium/Xiao-Phos-Catalyzed Asymmetric P-C Cross-Coupling of Secondary Phosphine Oxides and Aryl Bromides

The development of transition-metal-catalyzed methods for the synthesis of P-chiral phosphine derivatives poses a considerable challenge. Herein, we present a direct Pd/Xiao-Phos-catalyzed cross-coupling reaction of easily accessible secondary phosphine oxides and aryl bromides, which provides rapid access to P-chiral phosphine oxides. The reaction proceeds efficiently with a wide array of reaction partners to deliver various tertiary phosphine oxides in up to 96% yield and 97% ee. Moreover, the synthesis of DiPAMP ligand and its analogues was also realized, which demonstrates a suitable pathway to switching the branched chain of DiPAMP.

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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 synthetic approach to palmerolides via Negishi cross coupling. the challenge of the C15-C16 bond formation

The esterification of fragment C1-C8 (2) with fragment C16-C23 (3) to give iodo derivative 4, followed by a Pd-catalysed coupling with a C9-C15 fragment (7 or 8), may provide a common precursor of most palmerolides. Ligands and reaction conditions were exhaustively examined to perform the C15-C16 bond formation via Negishi reaction. With simple models, pre-activated Pd-Xantphos and Pd-DPEphos complexes were the most efficient catalysts at RT. Zincation of the C9-C15 fragment (8) and cross coupling with 4 required 3 equiv of t-BuLi, 10 mol % of Pd-Xantphos and 60 C.

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

Simple exploration of Pd2(DBA)3

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Palladium-catalyzed beta-(hetero)arylation of alpha,beta-unsaturated valerolactams

A method for the palladium-catalyzed arylation of alpha,beta-unsaturated valerolactams is reported. This new protocol provides arylation products in yields up to 95% and is applicable to a wide array of aryl and heteroaryl bromides. The optimization, scope and limitations are described.

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

Extracurricular laboratory:new discovery of Pd2(DBA)3

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Streamlined synthesis of the bippyphos family of ligands and cross-coupling applications

We describe the efficient preparation of Bippyphos, 1. The key precursor to Bippyphos, 5, was prepared via a one-pot bromination of diketone 2 followed by alkylation with pyrazole and condensation with phenylhydrazine. Lithiation of 5 and trapping with ditert-butylchlorophosphine afforded Bippyphos, 1. Using this approach we have prepared several derivatives of Bippyphos to probe the structure and activity relationships of this family of phosphine ligands. We also demonstrate the utility of these ligands in Pdcatalyzed amination reactions and other cross-coupling reactions.

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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 of pi-Conjugated Benzocyclotrimers

Polycyclic aromatic hydrocarbons (PAHs), especially three branchphene benzocyclotrimers represent a series of molecules with intriguing physical and chemical properties. Benzocyclotrimers are also important precursors to construct fullerenes and graphenes. In this article, we review the recent progress in the preparation methods of pi-conjugated benzocyclotrimers. In particular, cyclotrimerization reactions to construct varying shaped and edged benzocyclotrimers are illustrated. Various typical characterization methods for these materials, such as variable-temperature 1H-NMR, single crystal X-ray analysis, density functional theory (DFT) calculations and atomic force microscope (AFM) measurements are included for discussion.

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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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11C – labeled thiamine and derivatives thereof, labeled 11C – […], thiamine precursor, as well as PET probe using said imaging method (by machine translation)

PROBLEM TO BE SOLVED: To provide a compound such as thiamine, fursultiamine and derivatives thereof each having aC-labeled methyl group and a precursor thereof which are applicable to a PET method.SOLUTION: AC-labeled thiamine is represented by chemical structural formula (1) or (2) (wherein Xis a counter anion). There are providedC-labeled compounds from any of among prosultiamine, fursultiamine, octotiamine, allithiamine, thiamine disulfide, O-benzoyl thiamine disulfide, thiamine monophosphate disulfide, O, S-dibenzoylthiamine, S-benzoyl thiamine, benfotiamine, dicethiamine, cycothiamine, bisibuthiamine and bisbentiamine.

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

Discovery of Pd2(DBA)3

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Synthesis and redox reactions of bis(verdazyl)palladium complexes

The synthesis and ligand-centered redox chemistry of palladium complexes bearing two potentially bidentate verdazyl ligands is explored. Reaction of 1,5-diisopropyl-3-pyridin-2-yl-6-oxoverdazyl radical 1 with Pd(NCMe)4¡¤2BF4 gives a complex containing two coordinated verdazyl radicals. The structure of this complex consists of one verdazyl bound to Pd in a bidentate mode and the second verdazyl bound in a monodentate fashion through the pyridine substituent; the fourth coordination site is occupied by a solvent molecule (acetonitrile (3) or dimethyl sulfoxide (4)). Two-electron reduction of this complex with decamethylferrocene affords a bis(verdazyl) palladium complex (5) in which both verdazyls have been reduced to their anionic state and are both bound to Pd in bidentate manner. Complex 5 can be independently synthesized by a redox reaction between 1 and Pd2(dba)3. Reduced complex 5 can be re-oxidized to 3 or 4 with AgBF4; in contrast, oxidation with PhICl2 leads to ligand dissociation, ultimately giving radical 1 and a mono(verdazyl)dichloropalladium complex 2. One-electron oxidation using PhICl2 produces a formally “mixed valent” (in ligand) bis(verdazyl)chloropalladium complex (6) with one bidentate verdazyl anion ligand and one monodentate (pyridine-bound) verdazyl radical. Attempted protonation of the verdazyl ligands in complex 5 leads to complete ligand dissociation and protonation of both the tetrazine and pyridine moieties; deprotonation regenerates 5. Subsequent air oxidation of the tetrazane/pyridinium cation (formed as a tetrachloropalladate salt) leads to re-coordination of the verdazyl ligands to give 6 initially, but ultimately produces a combination of free radical 1 and 2.

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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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LiHMDS-Promoted Palladium-Catalyzed Sonogashira Cross-Coupling of Aryl Fluorides with Terminal Alkynes

A highly efficient Pd-catalyzed Sonogashira coupling of various aryl fluorides with terminal alkynes in the presence of LiHMDS was developed. Both unreactive electron-rich fluoroarenes and electron-poor fluoroarenes proceeded smoothly and afforded the corresponding internal alkynes in moderate to excellent yields.

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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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Process development, impurity control, and production of a novel tubulin inhibitor

Process development and production of a novel tubulin inhibitor are described. The desired API was obtained through selective iodination of the 12? position of vinblastine and subsequent thiomethylation. Most of the impurities were identified, and process parameters were adjusted to control such impurities. The optimized process was scaled up under cGMP conditions to afford 230 g of the desired API.

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