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Here we describe a self-assembling alpha,gamma-cyclic tetrapeptide that contains the 4-amino-3-hydroxytetrahydrofuran-2-carboxylic acid, in which the hydroxy group is pointing towards the inner cavity of the resulting dimers.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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A series of complexes with general formula M(Xan)2L2 (M = Ni(II), Xan = O-amyldithiocarbonato, L = 3-methylpyridine, 2,4-; 3,4-; 3,5-dimethylpyridines and 2,4,6-trimethylpyridine) have been synthesized and characterized by elemental analysis and various physico-chemical techniques such as magnetic susceptibility measurements, conductivity measurements, UV-Visible, Infrared spectral data. On the basis of electronic spectra and magnetic susceptibility measurements, an octahedral geometry has been proposed for all the complexes. IRspectral data shows that the substituted pyridines in all these complexes coordinate to the metal ion through nitrogen atoms occupying fifth and sixth axial positions where as O-alkyldithiocarbonate act as monoanion bidentate ligand and occupy the planar positions of octahedral structures. The X-ray diffraction analysis of one of the adducts bis(O-amyldithiocarbonato) bis(3,5-dimethylpyridine) nickel(II) is also investigated. The complex crystallizes in the monoclinic space group P21/c with unit cell parameters a = 9.167(2) A, b = 18.255(4) A, c = 9.299(2) A and beta = 103.47(2). The dihedral angle between dithio-groups and the pyridine ring is 88.9(1). The crystal structure of the molecule is stabilized by pi-pi interactions. Springer Science+Business Media New York 2012.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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The present application relates to novel substituted (aza)pyridopyrazolopyrimidinones and indazolopyrimidinones, to processes for their preparation, the compounds for use alone or in combinations in a method for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of acute and recurrent bleeding in patients with or without underlying hereditary or acquired bleeding disorders, wherein the bleeding is associated with a disease or medical intervention selected from the group consisting of menorrhagia, postpartum hemorrhage, hemorrhagic shock, trauma, surgery, transplantation, stroke, liver diseases, hereditary angioedema, nosebleed, and synovitis and cartilage damage following hemarthrosis.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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ConspectusNickel complexes exhibit distinct properties from other group 10 metals, including a small nuclear radius, high paring energy, low electronegativity, and low redox potentials. These properties enable Ni catalysts to accommodate and stabilize paramagnetic intermediates, access radical pathways, and undergo slow beta-H elimination. Our research program investigates how each of these fundamental attributes impact the catalytic properties of Ni, in particular in the context of alkene functionalization.Alkenes are versatile functional groups, but stereoselective carbofunctionalization reactions of alkenes have been underdeveloped. This challenge may derive from the difficulty of controlling selectivity via traditional two-electron migratory insertion pathways. Ni catalysts could lead to different stereodetermining steps via radical mechanisms, allowing access to molecular scaffolds that are otherwise difficult to prepare. For example, an asymmetric alkene diarylation reaction developed by our group relies upon the radical properties of Ni(III) intermediates to control the enantioselectivity and give access to a library of chiral alpha,alpha,beta-triarylethane molecules with biological activity.Mechanistic studies on a two-component reductive 1,2-difunctionalization reaction have shed light on the origin of the cross-electrophile selectivity, as C sp2 and C sp3 electrophiles are independently activated at Ni(I) via two-electron and radical pathways, respectively. Catalyst reduction has been identified to be the turnover-limiting step in this system. A closer investigation of the radical formation step using a (Xantphos)Ni(I)Ar model complex reveals that Ni(I) initiates radical formation via a concerted halogen-abstraction pathway.The low redox potentials of Ni have allowed us to develop a reductive, trans-selective diene cyclization, wherein a classic two-electron mechanism operates on a Ni(I)/Ni(III) platform, accounting for the chemo- and stereoselectivity. This reaction has found applications in the efficient synthesis of pharmaceutically relevant molecules, such as 3,4-dimethylgababutin.The tendency of Ni to undergo one-electron redox processes prompted us to explore dinuclear Ni-mediated bond formations. These studies provide insight into Ni-Ni bonding and how two metal centers react cooperatively to promote C-C, C-X, and N-N bond forming reductive elimination.Finally, isolation of beta-agostic Ni and Pd complexes has allowed for X-ray and neutron diffraction characterization of these highly reactive molecules. The bonding parameters serve as unambiguous evidence for beta-agostic interactions and help rationalize the slower beta-H elimination at Ni relative to Pd. Overall, our research has elucidated the fundamental properties of Ni complexes in several contexts. Greater mechanistic understanding facilitates catalyst design and helps rationalize the reactivity and selectivity in Ni-catalyzed alkene functionalization reactions.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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The transfer hydrogenation of ketones and imines using RuII, RhIII and IrIII complexes with beta-amino alkoxide and beta-amino sulphonimide ligands has been used for the last 20 years as a practical and powerful tool for the synthesis of alcohols and amines. When compared to Noyori hydrogenation under H2 pressure, e.g. catalysts of the type [(diphosphine)RuCl2(diamine)], which uses basic co-catalysts and requires access to pressure equipment, transfer hydrogenation is much more versatile and often more cost effective. The aim of this review is to highlight the large number of available process conditions that promise to give cost-efficient reductions of complex substrates, demonstrating the incredible versatility and effectiveness of this technology.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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The aryne [3 + 2] cycloaddition process with pyridinium imides breaks the aromaticity of the pyridine ring. By equipping the imide nitrogen with a sulfonyl group, the intermediate readily eliminates a sulfinate anion to restore the aromaticity, leading to the formation of pyrido[1,2-b]indazoles. The scope and limitation of this reaction are discussed. As an extension of this chemistry, N-tosylisoquinolinium imides, generated in situ from N?-(2-alkynylbenzylidene)-tosylhydrazides via an AgOTf-catalyzed 6-endo-dig electrophilic cyclization, readily undergo aryne [3 + 2] cycloaddition to afford indazolo[3,2-a]-isoquinolines in the same pot, offering a highly efficient route to these potential anticancer agents.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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An iridium-catalyzed asymmetric hydrogenation of unfunctionalized exocyclic C=C bonds was performed by using an axially flexible chiral phosphine?oxazoline ligand, providing the desired chiral 1-benzyl-2,3-dihydro-1H-indene products with up to 98 % ee (enantiomeric excess). This represents the first general hydrogenation of unfunctionalized exocyclic olefins with high selectivity reported thus far. The additive acetate ion plays an important role in the reaction’s high enantioselectivity. The chiral product can be further transformed into key intermediates required for the synthesis of an important insecticide and a drug compound.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Abstract: The reaction of cobalt(II) chloride with potassium myrtenate (KMyr) followed by addition of 2,3-lutidine in ethanol gives the trinuclear compound [Co3(Myr)6(2,4-Lut)2] (I). The central cobalt(II) atom is linked to each of the two other metal atoms by three myrtenic acid anions. The reaction of a solution of compound I with lithium myrtenate (LiMyr) results in the formation of tetranuclear heterometallic complex [Li2-Co2(Myr)6(2,4-Lut)2] (II). Compound II is composed of two binuclear {LiCo(Myr)3(2,4-Lut)} moieties, in which the lithium(I) atoms are linked to cobalt(II) atoms by bridging myrtenate anions. The lithium atoms are connected by two oxygen atoms of acid anions. Compounds I and II were characterized by X-ray diffraction (CIF files CCDC nos. 1898096 (I), 1898097 (II)).

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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The synthesis and SAR of HIV-1 protease inhibitors containing novel P2 structural elements are presented. The inhibitors were designed having hydrogen bond accepting P2 substituents to probe potential favorable interactions to Asp-29/Asp-30 of the HIV-1 protease backbone utilizing inhibitor 3 as a model template. Several inhibitors were synthesized from an l-Val methyl amide P2 motif by appending hydrogen bonding moieties from either the isopropyl side-chain or from the methyl amide portion. The most promising inhibitors 4a and 4e displayed Ki values of 1.0 nM and 0.7 nM respectively and EC50 values in the MT4 cell-based assay of 0.17 muM and 0.33 muM respectively, a slight loss in potency compared to lead inhibitor 3. These inhibitors were also tested against an HIV protease inhibitor resistant strain carrying the M46I, V82F, and I84V mutations. Inhibitors 4a and 4e displayed a 3 and 4 fold change respectively compared with HIV wild type, whereas lead inhibitor 3 showed a higher 9 fold change. This study further demonstrate the chemical tractability of the approach where various P2 substituents can be introduced in just one chemical step from lactone 21 enabling facile modifications of the overall properties in this inhibitor class.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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A rhodium-catalyzed regio- and enantioselective intermolecular allylation of malononitriles as masked acyl cyanides (MAC) with terminal and symmetrical internal allenes is reported. A RhI/Josiphos catalytic system combined with subsequent oxidative degradation of the primary adducts enables a straightforward access to alpha-branched, beta,gamma-unsaturated carbonyl compounds. The present protocol exhibits perfect atom economy in the allylation step and is characterized by a great functional group compatibility. Furthermore, the use of alpha-substituted malononitriles allowed for the construction of all-carbon quaternary centers.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis