Stereoselective synthesis of cis -3,4-disubstituted piperidines through ring transformation of 2-(2-Mesyloxyethyl)azetidines
Journal of Organic Chemistry, cilt.76, sa.20, ss.8364-8375, 2011 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 76 Sayı: 20
- Basım Tarihi: 2011
- Doi Numarası: 10.1021/jo201556t
- Dergi Adı: Journal of Organic Chemistry
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.8364-8375
- Boğaziçi Üniversitesi Adresli: Evet
Özet
The reactivity of 2-(2-mesyloxyethyl)azetidines, obtained through monochloroalane reduction and mesylation of the corresponding Β-lactams, with regard to different nucleophiles was evaluated for the first time, resulting in the stereoselective preparation of a variety of new 4-acetoxy-, 4-hydroxy-, 4-bromo-, and 4-formyloxypiperidines. During these reactions, transient 1-azoniabicyclo[2.2.0]hexanes were prone to undergo an S N2-type ring opening to afford the final azaheterocycles, which was rationalized by means of a detailed computational analysis. This approach constitutes a convenient alternative for the known preparation of 3,4-disubstituted 5,5-dimethylpiperidines, providing an easy access to the 5,5-nor-dimethyl analogues as valuable templates in medicinal chemistry. Furthermore, cis-4-bromo-3-(phenoxy or benzyloxy)piperidines were elaborated into the piperidin-3-one framework via dehydrobromination followed by acid hydrolysis. © 2011 American Chemical Society.