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A direct access to 3,5-disubstituted isoxazoles has been accomplished through an intramolecular oxidative coupling reaction of enone oximes using a catalytic quantity of Cu(OAc)2. This method features an inexpensive metal catalyst, molecular oxygen as a green oxidant, good functional group tolerance and readily available starting materials. This attractive method for the synthesis of isoxazole derivatives is of great significance due to the product’s versatile reactivity for further transformations.

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The generation of gold carbenes via the gold-catalyzed intermolecular reaction of nucleophiles containing relatively labile N-O or N-N bonds with alkynes has received considerable attention during recent years. However, this protocol is not atom-economic as the reaction produces a stoichiometric amount of pyridine or quinoline waste, the cleaved part of the N-O or N-N bonds. In this article, we disclose an unprecedented gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles, allowing rapid and practical access to a wide range of synthetically-useful 2-aminopyrroles. Most importantly, mechanistic studies and theoretical calculations revealed that this reaction presumably proceeds via an alpha-imino gold carbene pathway, thus providing a strategically novel, atom-economic route to the generation of gold carbenes. Other significant features of this approach include the use of readily-available starting materials, high flexibility, simple procedure, mild reaction conditions, and in particular, no need to exclude moisture or air (“open flask”).

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Gold-catalyzed tandem cyclization-oxidative alkynylation and cyclization-fluorination reactions of 2-alkynone O-methyloximes are described. The reactions proceed smoothly at room temperature in the presence of 10 mol % of (PPh3)AuNTf2, 2.5 equivalents of selectfluor, and 2 equivalents of K3PO4. 2-Alkynone O-methyloximes undergo intramolecular oxyauration/cyclization and ensuing oxidative cross-coupling and fluorination process to afford the corresponding 3,4,5-trisubstituted isoxazoles in a cascade manner.

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A simple, efficient and eco-friendly method has been developed for the condensation of hydroxylamine hydrochloride with aldehydes, ketones and 1,3-diketones in the presence of powdered molecular sieves (3A) as catalyst. Aldoximes, ketoximes and 1,3-dioximes were obtained in excellent yields.

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The present invention relates to novel substituted imidazo[1,2-b]pyridazine compounds of Formula (I): pharmaceutical compositions thereof, and the use such compounds as corticotropin releasing factor 1 (CRF1) receptor antagonists in the treatment of psychiatric disorders and neurological diseases.

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C?N bond formation is regarded as a very useful and fundamental reaction for the synthesis of nitrogen-containing molecules in both organic and pharmaceutical chemistry. Noble-metal and homogeneous catalysts have frequently been used for C?N bond formation, however, these catalysts have a number of disadvantages, such as high cost, toxicity, and low atom economy. In this work, a low-toxic and cheap iron complex (iron ethylene-1,2-diamine) has been loaded onto carbon nanotubes (CNTs) to prepare a heterogeneous single-atom catalyst (SAC) named Fe-Nx/CNTs. We employed this SAC in the synthesis of C?N bonds for the first time. It was found that Fe-Nx/CNTs is an efficient catalyst for the synthesis of C?N bonds starting from aromatic amines and ketones. Its catalytic performance was excellent, giving yields of up to 96 %, six-fold higher than the yields obtained with noble-metal catalysts, such as AuCl3/CNTs and RhCl3/CNTs. The catalyst showed efficacy in the reactions of thirteen aromatic amine substrates, without the need for additives, and seventeen enaminones were obtained. High-angle annular dark-field scanning transmission electron microscopy in combination with X-ray absorption spectroscopy revealed that the iron species were well dispersed in the Fe-Nx/CNTs catalyst as single atoms and that Fe-Nx might be the catalytic active species. This Fe-Nx/CNTs catalyst has potential industrial applications as it could be cycled seven times without any significant loss of activity.

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Domino oxidation of primary alcohols to alpha,beta-unsaturated compounds using the combination of PCC-NaOAc and stabilized Wittig reagent and its application towards total synthesis of ABT-418 and 4-oxonon-2-enoic acid is described.

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We report a highly enantioselective Pd-PHOX-catalyzed intermolecular hydroalkylation of acyclic 1,3-dienes. Meldrum’s acid derivatives and other activated C-pronucleophiles, such as beta-diketones and malononitriles, react with a variety of aryl- and alkyl-substituted dienes in ?20 h at room temperature. The coupled products, obtained in up to 96% yield and 97.5:2.5 er, are easily transformed into useful chemical building blocks for downstream synthesis.

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A concise, regiocontrolled route to isoxazoles, based on the condensation of an ester with a metallated imine, has been developed. The intermediate vinylogous amides react smoothly with hydroxylamine to provide, after dehydration, substituted isoxazoles. The method has been used for the multi-kilo scale preparation of ABT-418, a novel cholinergic channel activator.

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3,5-Disubstituted isoxazole derivatives, when irradiated in the presence of pentacarbonyliron and water undergo reductive cleavage of the N-O bond to give beta-aminoenones in good yields.

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