Synthesis of 5-(Fluoroalkyl)isoxazole Building Blocks by Regioselective Reactions of Functionalized Halogenoximes
| العنوان: | Synthesis of 5-(Fluoroalkyl)isoxazole Building Blocks by Regioselective Reactions of Functionalized Halogenoximes |
|---|---|
| المؤلفون: | Oleksandr V. Borysov, Iulia Bakanovych, Yurii S. Moroz, Oleksandr O. Grygorenko, Yulia V Fil, Bohdan A. Chalyk, Kateryna V. Hrebeniuk, Pavlo S. Lebed, Bohdan V. Vashchenko, Alexander B. Rozhenko, Angelina V. Biitseva, Konstantin S. Gavrilenko |
| المصدر: | J Org Chem |
| بيانات النشر: | American Chemical Society (ACS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Molecular Structure, 010405 organic chemistry, Organic Chemistry, Regioselectivity, Stereoisomerism, Alcohol, Isoxazoles, 010402 general chemistry, 01 natural sciences, Combinatorial chemistry, Article, Cycloaddition, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Cyclization, Reagent, Yield (chemistry), Oximes, Nucleophilic substitution, Isoxazole |
| الوصف: | A comprehensive study on the synthesis of 5-fluoroalkyl-substituted isoxazoles starting from functionalized halogenoximes is reported. One-pot metal-free [3 + 2] cycloaddition of CF3-substituted alkenes and halogenoximes bearing ester, bromo, chloromethyl, and protected amino groups was developed for the preparation of 5-trifluoromethylisoxazoles. The target 3,5-disubstituted derivatives were obtained in a regioselective manner in good to excellent yield on up to 130 g scale. 5-Fluoromethyl- and 5-difluoromethylisoxazoles were synthesized by late-stage deoxofluorination of the corresponding 5-hydroxymethyl or 5-formyl derivatives, respectively, in turn prepared via metal-free cycloaddition of halogenoximes and propargylic alcohol. An alternative approach based on nucleophilic substitution in 5-bromomethyl derivatives was found to be more convenient for the preparation of 5-fluoromethylisoxazoles. Reaction of isoxazole-5-carbaldehydes with the Ruppert-Prakash reagent was used for the preparation of (β,β,β-trifluoro-α-hydroxyethyl)isoxazoles. Utility of described approaches was shown by multigram preparation of side-chain functionalized mono-, di-, and trifluoromethylisoxazoles, for example, fluorinated analogues of ABT-418 and ESI-09. |
| تدمد: | 1520-6904 0022-3263 |
| DOI: | 10.1021/acs.joc.9b02264 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d950327e0635755320bd63d84cd83be4 https://doi.org/10.1021/acs.joc.9b02264 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d950327e0635755320bd63d84cd83be4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15206904 00223263 |
|---|---|
| DOI: | 10.1021/acs.joc.9b02264 |