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Development of a scalable route to a dual NK-1/serotonin receptor antagonist

The evolution of a process for the preparation of a new heterocyclic dual NK1/serotonin receptor antagonist is described. The final synthesis features a telescoped sequence in which an iron(III)-catalyzed Grignard coupling is followed by a benzylic chlorination utilizing trichlorocyanuric acid to construct an unsymmetrical 2,4,6-trisubstituted pyridine. Etherification of a 4,4?-arylhydroxymethane substituted piperidine fragment completes the synthesis of the active pharmaceutical ingredient in 44% overall yield.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Modular synthesis of triarylmethanes through palladium-catalyzed sequential arylation of methyl phenyl sulfone

Triarylmethanes, which are valuable structures in materials, sensing and pharmaceuticals, have been synthesized starting from methyl phenyl sulfone as an inexpensive and readily available template. The three aryl groups were installed through two sequential palladium-catalyzed C-H arylation reactions, followed by an arylative desulfonation. This method provides a new synthetic approach to multisubstituted triarylmethanes using readily available haloarenes and aryl boronic acids, and is also valuable for the preparation of unexplored triarylmethane-based materials and pharmaceuticals. Unsymmetric triarylmethanes have been synthesized starting from methyl phenyl sulfone as an inexpensive and readily available template. The three aryl groups were installed through two sequential palladium-catalyzed C-H arylation reactions, followed by an arylative desulfonation. Copyright

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Current methodologies for a sustainable approach to pi-conjugated organic semiconductors

The most effective synthetic methodologies currently employed for producing polymeric semiconductors are affected by cost, safety, and environmental issues which may seriously prevent their large-scale production. In this regard, the application of principles of green chemistry for the development of waste-minimized and cleaner synthetic approaches to semiconductor synthesis is essential for propelling the field of organic electronics. In this review, selected advances in the development of synthetic green strategies for the preparation of poly(arylene) families as well as their implication in the performance of selected opto-electronic devices such as organic thin-film transistors and bulk heterojunction solar cells are summarized.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Access to Divergent Fluorinated Enynes and Arenes via Palladium-Catalyzed Ring-Opening Alkynylation of gem-Difluorinated Cyclopropanes

Herein, we describe a palladium-catalyzed alkynylation of gem-difluorinated cyclopropanes via C-C bond activation/C-F bond cleavage, followed by C-C(sp) coupling. The new approach proceeds with broad substrate scope under mild reaction conditions, whereas both 1,1-disubstituted and complex-molecule-modified gem-difluorinated cyclopropanes react smoothly with high stereoselectivity. The developed method provides efficient and convenient ways access to diversity of important fluorinated enynes and arenes by slightly modification of the reaction conditions.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Efficient synthesis of thieno[3,2-b:4,5-b?]diindoles and benzothieno[3,2-b]indoles by Pd-catalyzed site-selective C-C and C-N coupling reactions

Heteroacenes (thieno[3,2-b:4,5-b?]diindoles and benzothieno[3,2-b] indoles) were efficiently synthesized from tetrabromothiophene and 2,3-dibromobenzothiophene in two steps, respectively. In the first step, a site-selective Pd-catalyzed C-C coupling is carried out, followed by a two-fold C-N coupling with aromatic and aliphatic amines.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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One-pot three-component sulfone synthesis exploiting palladium-catalysed aryl halide aminosulfonylation

A palladium-catalysed aminosulfonylation process is used as the key-step in a one-pot, three-component sulfone synthesis. The process combines aryl-, heteroaryl- and alkenyl iodides with a sulfonyl unit and an electrophilic coupling fragment. The sulfonyl unit is delivered in the form of an aminosulfonamide, which then serves as a masked sulfinate. The sulfinate is combined, in situ, with an electrophilic coupling partner, such as a benzylic, allylic or alkyl halide, an electron-poor arene, or a cyclic epoxide, to provide the corresponding sulfone products in good to excellent yields. The mild reaction conditions and use of commercially available reaction components allows the easy preparation of a broad range of sulfones featuring a variety of functional groups. The process obviates the need to employ thiol starting materials, and oxidative operations.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Development of a practical, asymmetric synthesis of the hepatitis C virus protease inhibitor MK-5172

The development of a practical, asymmetric synthesis of the hepatitis C virus (HCV) protease inhibitor MK-5172 (1), an 18-membered macrocycle, is described.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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A convergent approach to (-)-callystatin a based on local symmetry

The key is symmetry! A convergent synthetic approach of the highly cytotoxic natural product (-)-callystatin A was developed assembling three fragments through Julia-Kocienski olefination and Stille cross-coupling. The new strategy relies on a pivotal local symmetry of the target molecule. In this preliminary study, particular attention was devoted to facilitate the catalytic enantiocontrol of strategic stereogenic centers present in each of the fragments (see scheme). Copyright

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation

Phosphatidylinositol-3-kinase alpha (PI3Kalpha) is a therapeutic target of high interest in anticancer drug research. On the basis of a binding model rationalizing the high selectivity and potency of a particular series of 2-aminothiazole compounds in inhibiting PI3Kalpha, a medicinal chemistry program has led to the discovery of the clinical candidate NVP-BYL719.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

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HETEROCYCLIC NUCLEAR HORMONE RECEPTOR MODULATORS

Provided are fused bicyclic compounds of Formula (I) effective to modulate the glucocorticoid receptor, wherein X, Y, Z, M, Q, L, J, G, E, A, Ring 1 and 2 are defined as in the description. Also provided herein are a pharmaceutical composition thereof, and uses in the manufacture of a medicament for treating corresponding disease thereof.

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Reference£º
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate