| Autor: |
Chalyk, Bohdan A., Khutorianskyi, Andrii V., Vashchenko, Bohdan V., Danyleiko, Kyrylo, Grynyova, Anastasiia, Osipova, Anastasiia O., Kozytskiy, Andriy, Syniuchenko, Darya, Tsymbaliuk, Anton, Gavrilenko, Konstantin S., Biitseva, Angelina V., Volochnyuk, Dmitriy M., Komarov, Igor V., Grygorenko, Oleksandr O. |
| Zdroj: |
The Journal of Organic Chemistry; January 2022, Vol. 87 Issue: 2 p1001-1018, 18p |
| Abstrakt: |
An efficient synthesis (up to a 200 g scale) of 3-hydroxypyrrolidin-2-ones bearing alkyl substituents or functional groups at the C-5 position is described. The reaction sequence started from 1,3-dipolar cycloaddition of in situgenerated nitrile oxides with (meth-)acrylates into 3-substituted isoxazoline-5-carboxylates. The catalytic hydrogenolysis of the isoxazoline N–O bond was optimal upon using H2(1 atm) at rt, with the following order of the catalyst activity: Pd–C > Pd(OH)2–C > Pt–C. The reactions with Pt–C were more selective for the synthesis of pyrrolidones, while Pd–C provided the fastest conversion rates. The stirring efficiency had a positive impact on conversion rather than elevated temperatures (up to 40 °C) or pressure (up to 50 atm). The diastereoselectivity was governed mainly by steric factors, with a dr of 1:1 to 3:1 (cis-and trans-isomers could be separated). Higher homologues (isoxazolinylacetates and -propanoates) were suitable for the synthesis of 6- or 7-substituted 4-hydroxypiperidones and 5-hydroxyazepanones, respectively. The proposed methods are tolerant to functional groups, including CF3(but not CHF2or CH2Cl), ester, and most N-Boc-protected amines. The utility of hydroxyl groups in lactams was shown by functional group transformations. Hydrogenolysis of C(5)-functionalized isoxazolines, bearing trimethylsilyl, phosphonate, or sulfone groups, was also studied to demonstrate limitations. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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