Asymmetric synthesis of 3,4-disubstituted 2-(trifluoromethyl)pyrrolidines through rearrangement of chiral 2-(2,2,2-trifluoro-1-hydroxyethyl)azetidines
Journal of Organic Chemistry, cilt.82, sa.19, ss.10092-10109, 2017 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 82 Sayı: 19
- Basım Tarihi: 2017
- Doi Numarası: 10.1021/acs.joc.7b01241
- Dergi Adı: Journal of Organic Chemistry
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.10092-10109
- Boğaziçi Üniversitesi Adresli: Evet
Özet
Enantiopure 4-formyl-β-lactams were deployed as synthons for the diastereoselective formation of chiral 2-(2,2,2-trifluoro-1-hydroxyethyl)azetidines via trifluoromethylation through aldehyde modification followed by reductive removal of the β-lactam carbonyl moiety. Subsequent treatment of the (in situ) activated 2-trifluoroethylated azetidines with a variety of nitrogen, oxygen, sulfur, and fluorine nucleophiles afforded chiral 3,4-disubstituted 2-(trifluoromethyl)pyrrolidines in good to excellent yields (45-99%) and high diastereoselectivities (dr >99/1, 1H NMR) via interception of bicyclic aziridinium intermediates. Furthermore, representative pyrrolidines were N,O-debenzylated in a selective way and used for further synthetic elaboration to produce, for example, a CF3-substituted 2-oxa-4,7-diazabicyclo[3.3.0]octan-3-one system.