Expedient Organocatalytic Syntheses of 4-Substituted Pyrazolidines and Isoxazolidines

• Published in: Molecules (Basel, Switzerland) Vol. 21; no. 12; p. 1655
• Main Authors: Yousfi, Tarek, Elliott, Alysha, Hanane, Messiad, Merdes, Rachid, Moyano, Albert
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2016; MDPI
• Subjects: Amino acids; asymmetric catalysis; Catalysis; Catàlisi asimètrica; enals; Enantioselective catalysis; hydrazines; hydroxylamines; isoxazolidinones; organocatalysis; Oxazoles - chemical synthesis; Oxazoles - chemistry; Oxidation; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; pyrazolidinones; Algeria; organocatalysis; isoxazolidinones; hydrazines; pyrazolidinones; asymmetric catalysis; hydroxylamines; enals
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21121655

The efficient organocatalytic synthesis of heterocyclic systems of biological relevance is a subject of growing interest. We have found that the pyrrolidine/benzoic acid-catalyzed reaction of α-substituted propenals such as methacrolein, 2-benzylpropenal and 2-(n-hexyl)propenal with activated hydrazines takes place in very good yields (83%–99.6%) under very mild conditions to afford 4-substituted pyrazolidin-3-ols (as diastereomer mixtures); subsequent oxidation with PCC affords the corresponding-4-substituted-3-pyrazolidinones in essentially quantitative yields. In a similar way, 4-substituted isoxazolidinones are obtained with N-Cbz-hydroxylamine as a reagent. The use of chiral diarylprolinol trimethylsilyl ethers as catalysts allows the synthesis of several of these compounds in optically active form, in some cases with excellent enantioselectivity (up to 96:4 er). A preliminary evaluation of the biological activity shows that some of these compounds exhibit interesting antibacterial and antifungal activities.