Practical stereoselective synthesis of an alpha-trifluoromethyl-alpha-alkyl epoxide via a diastereoselective trifluoromethylation reaction.
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.
Song
Jinhua J
JJ
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
Tan
Zhulin
Z
Xu
Jinghua
J
Reeves
Jonathan T
JT
Yee
Nathan K
NK
Ramdas
Ranjit
R
Gallou
Fabrice
F
Kuzmich
Katie
K
Delattre
Lisa
L
Lee
Heewon
H
Feng
Xuwu
X
Senanayake
Chris H
CH
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
D004852:Epoxy Compounds; D004952:Esters; D005461:Fluorine