Synthesis of 5-(Fluoroalkyl)isoxazole Building Blocks by Regioselective Reactions of Functionalized Halogenoximes.

Autor:	Chalyk BA; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.; Institute of Organic Chemistry , National Academy of Sciences of Ukraine , Murmanska Street 5 , Kyiv 02660 , Ukraine., Hrebeniuk KV; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine., Fil YV; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine., Gavrilenko KS; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.; Taras Shevchenko National University of Kyiv , Volodymyrska Street 60 , Kyiv 01601 , Ukraine., Rozhenko AB; Institute of Organic Chemistry , National Academy of Sciences of Ukraine , Murmanska Street 5 , Kyiv 02660 , Ukraine., Vashchenko BV; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.; Taras Shevchenko National University of Kyiv , Volodymyrska Street 60 , Kyiv 01601 , Ukraine., Borysov OV; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.; Institute of Organic Chemistry , National Academy of Sciences of Ukraine , Murmanska Street 5 , Kyiv 02660 , Ukraine., Biitseva AV; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.; Taras Shevchenko National University of Kyiv , Volodymyrska Street 60 , Kyiv 01601 , Ukraine., Lebed PS; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.; Taras Shevchenko National University of Kyiv , Volodymyrska Street 60 , Kyiv 01601 , Ukraine., Bakanovych I; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.; Taras Shevchenko National University of Kyiv , Volodymyrska Street 60 , Kyiv 01601 , Ukraine., Moroz YS; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.; Chemspace , Ilukstes iela 38-5 , Riga LV-1082 , Latvia., Grygorenko OO; Enamine Ltd , (www.enamine.net), Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.; Taras Shevchenko National University of Kyiv , Volodymyrska Street 60 , Kyiv 01601 , Ukraine.
Jazyk:	angličtina
Zdroj:	The Journal of organic chemistry [J Org Chem] 2019 Dec 20; Vol. 84 (24), pp. 15877-15899. Date of Electronic Publication: 2019 Oct 30.
DOI:	10.1021/acs.joc.9b02264
Abstrakt:	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 CF 3 -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.
Databáze:	MEDLINE
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