title: Practical stereoselective synthesis of an alpha-trifluoromethyl-alpha-alkyl epoxide via a diastereoselective trifluoromethylation reaction.
abstract: A practical stereoselective synthesis is reported for an alpha-trifluoromethyl-alpha-alkyl epoxide (1), which is an important pharmaceutical intermediate. The key step involves a chiral auxiliary-controlled asymmetric trifluoromethylation reaction for the introduction of the unique trifluoromethyl-substituted tertiary alcohol stereogenic center in the target molecule. The fluoride-initiated CF3 addition to chiral keto ester 6a proceeded with a diastereoselectivity up to 86:14. The major diastereomer was readily obtained with a >99.5:0.5 dr through a simple crystallization of the crude product mixture.
authors.affiliation: Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Old Ridgebury Road/P O Box 368, Ridgefield, Connecticut 06877-0368, USA. jsong@rdg.boehringer-ingelheim.com
authors.forename: Jinhua J
authors.initials: JJ
authors.lastname: Song
authors.forename: Zhulin
authors.initials: Z
authors.lastname: Tan
authors.forename: Jinghua
authors.initials: J
authors.lastname: Xu
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Reeves
authors.forename: Nathan K
authors.initials: NK
authors.lastname: Yee
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ramdas
authors.forename: Fabrice
authors.initials: F
authors.lastname: Gallou
authors.forename: Katie
authors.initials: K
authors.lastname: Kuzmich
authors.forename: Lisa
authors.initials: L
authors.lastname: Delattre
authors.forename: Heewon
authors.initials: H
authors.lastname: Lee
authors.forename: Xuwu
authors.initials: X
authors.lastname: Feng
authors.forename: Chris H
authors.initials: CH
authors.lastname: Senanayake
mesh_terms: D000478:Alkylation; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D004852:Epoxy Compounds; D004952:Esters; D005461:Fluorine