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. 2025 Feb 12;10(7):6663-6670.
doi: 10.1021/acsomega.4c08062. eCollection 2025 Feb 25.

Asymmetric Synthesis of Functionalized 2-Isoxazolines

Beyza Hamur  1 , Fatma Albayrak Halac  1 , Fethiye Yilmazer  1 , Fraser F Fleming  2 , Irem Kulu  1 , Ramazan Altundas  1
Affiliations

Asymmetric Synthesis of Functionalized 2-Isoxazolines

Beyza Hamur et al. ACS Omega. .

Abstract

The asymmetric synthesis of the isoxazoline skeleton was achieved by the oxidation of hydroxylaminoalkyl furan prepared from simple starting materials: 2-methylfuran and (S)-epichlorohydrin. The synthesis features an NBS-mediated oxidation of hydroxylaminoalkyl furan to give an α,β-unsaturated ketone intermediate which cyclized to the isoxazoline. The α,β-unsaturated double bond was successfully cleaved with RuCl3·xH2O catalysis en route to the isoxazoline skeleton bearing alcohol, aldehyde, and carboxylic acid functionalities.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. (a) n-BuLi, THF, −78 °C, Then (S)-Epichlorohydrin, BF3·OEt2, −78 °C to rt, N2; (b) PPh3, NHPI, THF, DEAD, 0 °C to reflux, N2; (c) NH2NH2·xH2O, CH2Cl2, rt, N2; and (d) Et3N, Boc2O, THF, 0 °C, N2
Scheme 2
Scheme 2. (a) NaHCO3, NaOAc, NBS, THF, 0 °C to rt; (b) p-TSA, CH2Cl2, rt; (c) O2, TPP, hv, CH2Cl2, 0 °C; and (d) Me2S
Scheme 3
Scheme 3. (a) RuCl3·xH2O, NaIO4, EtOAc, ACN, H2O, rt and (b) NaBH4, MeOH, 0 °C, and H+/H2O
Scheme 4
Scheme 4. (a) RuCl3·xH2O, NaIO4, DCE, H2O, rt; (b) NaBH4, MeOH, 0 °C, and H+/H2O; and (c) Jones Reagent, Acetone, rt
Scheme 5
Scheme 5. (a) NaN3, DMSO, 60 °C
Scheme 6
Scheme 6. (a) SOCl2, MeOH, 0 °C to rt and (b) NaN3, DMSO, 60 °C
See this image and copyright information in PMC

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