title: Synthesis of enantiopure trans-2,5-disubstituted trifluoromethylpyrrolidines and (2S,5R)-5-trifluoromethylproline.
abstract: Enantiopure trans-2,5-disubstituted trifluoromethylpyrrolidines were prepared on a several gram scale starting from a readily available chiral fluorinated oxazolidine (Fox). A pure oxazolopyrrolidine intermediate could be obtained after an efficient separation by selective diastereomer destruction. The addition of various Grignard reagents on this oxazolopyrrolidine provided disubstituted pyrrolidines with moderate to complete trans diastereoselectivity. The highly valuable compound (2S,5R)-5-trifluoromethylproline could be synthesized from the same oxazolopyrrolidine intermediate via a Strecker-type reaction.
authors: Laboratoire de Chimie Biologique (LCB), Université de Cergy-Pontoise , 5 Mail Gay-Lussac, 95000 Cergy-Pontoise cedex, France.
authors: Hodney
authors: H
authors: Lubin
authors: Julien
authors: J
authors: Pytkowicz
authors: Grégory
authors: G
authors: Chaume
authors: Gwenaëlle
authors: G
authors: Sizun-Thomé
authors: Thierry
authors: T
authors: Brigaud
mesh_terms: D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: C000601916:5-trifluoromethylproline; D006845:Hydrocarbons, Fluorinated; D007202:Indicators and Reagents; D010080:Oxazoles; D011759:Pyrrolidines; C064210:oxazolidine; D011392:Proline