Asymmetric hydrogenation of protected allylic amines.
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.
Steinhuebel
Dietrich P
DP
Department of Process Research, Merck & Co. Inc., PO Box 2000, Rahway, New Jersey 07065, USA. dietrich_steinhuebel@merck.com
Krska
Shane W
SW
Alorati
Anthony
A
Baxter
Jenny M
JM
Belyk
Kevin
K
Bishop
Brian
B
Palucki
Michael
M
Sun
Yongkui
Y
Davies
Ian W
IW
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
D000498:Allyl Compounds; D000588:Amines; D001381:Azepines; D007093:Imidazoles; D002209:Caprolactam; C525458:telcagepant