title: Asymmetric hydrogenation of protected allylic amines.
abstract: A general method for the enantioselective hydrogenation of protected allylic amine derivatives is described. This procedure relies on the generation of a cationic ruthenium complex with the axially chiral ligand (-)-TMBTP. The utility is highlighted by the highly enantioselective hydrogenation of a diene substrate that can then be elaborated to prepare Telcagepant, a compound currently in Phase III clinical trials. The scope of the hydrogenation reaction was studied, and a variety of substituted allylic amine derivatives could be hydrogenated with enantiomeric ratios of 92:8 or higher.
authors.affiliation: Department of Process Research, Merck & Co. Inc., PO Box 2000, Rahway, New Jersey 07065, USA. dietrich_steinhuebel@merck.com
authors.forename: Dietrich P
authors.initials: DP
authors.lastname: Steinhuebel
authors.forename: Shane W
authors.initials: SW
authors.lastname: Krska
authors.forename: Anthony
authors.initials: A
authors.lastname: Alorati
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Baxter
authors.forename: Kevin
authors.initials: K
authors.lastname: Belyk
authors.forename: Brian
authors.initials: B
authors.lastname: Bishop
authors.forename: Michael
authors.initials: M
authors.lastname: Palucki
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Sun
authors.forename: Ian W
authors.initials: IW
authors.lastname: Davies
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D001381:Azepines / Q000138:chemical synthesis; D002209:Caprolactam / Q000138:chemical synthesis; D002384:Catalysis; D006865:Hydrogenation; D007093:Imidazoles / Q000138:chemical synthesis; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000498:Allyl Compounds; D000588:Amines; D001381:Azepines; D007093:Imidazoles; D002209:Caprolactam; C525458:telcagepant