A Short and Versatile Approach for the Synthesis of Pyrrolizidinones
Helvetica Chimica Acta, cilt.105, sa.3, 2022 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 105 Sayı: 3
- Basım Tarihi: 2022
- Doi Numarası: 10.1002/hlca.202100226
- Dergi Adı: Helvetica Chimica Acta
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, Aquatic Science & Fisheries Abstracts (ASFA), Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, Veterinary Science Database, DIALNET
- Anahtar Kelimeler: Beckmann rearrangement, cycloaddition, keteniminium salts, nucleophilic substitution, pyrrolizidine, pyrrolizidinone
- Boğaziçi Üniversitesi Adresli: Evet
Özet
Herein we describe a novel 3-step synthesis of pyrrolizidinone derivatives with good overall yield. This sequence relies on first a [2+2] cycloaddition between a keteniminium salt intermediate, bearing an alkyl chloride side chain, and an alkene partner furnishing the corresponding cyclobutanone after hydrolysis of the resulting cyclobutaniminium. Then ring expansion towards the γ-lactam using a Beckmann-type rearrangement followed by intramolecular SN2 reaction in the presence of a base triggers the second ring formation of the process. This approach, which is particularly straightforward, allows a broad diversification of pyrrolizidinones by changing the nature of the substituents on the starting alkene and on the keteniminium precursor. Additionally, a computational study was conducted to assess the activation barrier of the SN2 step on different intermediates as well as the nitrogen pyramidalization of the resulting pyrrolizidinones adducts.