Synthesis of ethyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylate via regioselective dipolar cycloaddition

Schmidt, Michael A.; Katipally, Kishta; Ramı́rez, Antonio; Soltani, Omid; Hou, Xiaoping; Zhang, Huiping; Chen, Bang‐Chi; Qian, Xinhua; Deshpande, Rajendra P.

doi:10.1016/j.tetlet.2012.05.089

Cited by 17 publications

(18 citation statements)

References 28 publications

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“…The proposed mechanism involves the following steps: (i) regioselective cycloaddition; (ii) cyclopropane ring opening; and (iii) rearomatization. In another study, Schmidt and co‐workers developed a regioselective [3+2] cycloaddition between phenyl nitrile oxide and trifluoromethyl crotonates (Scheme B) 37. The reaction provides 4‐trifluoromethylisoxazoles bearing various electron.withdrawing groups (e.g., esters, acids) in good yields.…”

Section: Synthesis Of Isoxazoles Via [3+2] Cycloaddition Reactionsmentioning

confidence: 99%

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β‐Cyclodextrin–Glycerol Dimers: Synthesis and NMR Conformational Analysis

Legros¹,

Vanhaverbeke²,

Souard³

et al. 2013

Eur J Org Chem

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The synthesis of new β‐cyclodextrin dimers linked through their primary faces by different glycerol‐like moieties by click chemistry is described. The unusual behaviour of these cyclodextrin–glycerol dimers in aqueous solution has been studied by NMR spectroscopy. We show that, depending on the length of the linking arm between the two cyclodextrins, the dimers could adopt very different conformations in water: symmetrical or pseudo[1]rotaxane‐like structures through one D‐glucopyranose unit tumbling in one β‐cyclodextrin.

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Section: Synthesis Of Isoxazoles Via [3+2] Cycloaddition Reactionsmentioning

confidence: 99%

“… Regioselective synthesis of functionalized 4‐substituted isoxazoles by nitrile oxide [3+2] cycloaddition. A: Wang;36 B: Schmidt 37…”

Section: Synthesis Of Isoxazoles Via [3+2] Cycloaddition Reactionsmentioning

confidence: 99%

β‐Cyclodextrin–Glycerol Dimers: Synthesis and NMR Conformational Analysis

Legros¹,

Vanhaverbeke²,

Souard³

et al. 2013

Eur J Org Chem

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“…A classical approach to the synthesis of these compounds relies on the heterocyclization reaction of fluorinated 1,3-bis-electrophiles and hydroxylamine (Scheme , A). − A similar method involves condensation of enolizable oximes with trifluoroacetates (Scheme , B) . In addition to that, deoxofluorination of the oxygen-containing isoxazoles, for example, alcohols or aldehydes, was described (Scheme , C). , An alternative approach includes [3 + 2] cycloaddition − of fluoroalkyl-substituted alkenes, − alkynes, − or enolizable ketones − and generated in situ nitrile oxides (Scheme , D). To the best of our knowledge, many examples of aforementioned [3 + 2] cycloadditions were not regioselective under reported conditions. − In other cases, when 5-(fluoroalkyl)isoxazoles were the desired product, the observed regioselectivity led to target compounds only as a minor product. ,, Moreover, the limited substrate scope was typically demonstrated, often including only aryl-substituted nitrile oxides.…”

Section: Introductionmentioning

confidence: 99%

“…To date, only a few examples of similar reactions with trifluoromethyl-substituted substrates were described in the literature, being limited to simple alkyl- or benzonitrile oxides and α,β-unsaturated esters (Scheme ). ,, …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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“…Peptide chains were grown on Rink-amide resin, and TBTU/HOBt/DIPEA system was used for coupling. Only in the case of Ac-Leu-AlaIso-Val-NH 2 (18) we observed minor degree of epimerization (#15%), whereas in Ac- Leu-Val-AlaIso-NH 2 (19) no racemization was observed. 37 In addition, no degradation was found aer cleavage from the resin upon treatment with TFA/TIS.…”

Section: Practical Applicationsmentioning

confidence: 70%