Ruthenium-catalyzed selective α,β-deuteration of bioactive amines.
A novel and convenient protocol for the catalytic hydrogen-deuterium exchange of biologically active tertiary amines utilizing the borrowing hydrogen methodology has been developed. In the presence of the readily available Shvo catalyst, excellent chemoselectivity toward α- and β-protons with respect to the nitrogen atom as well as high degree of deuterium incorporation and functional group tolerance is achieved. This allowed for the deuteration of complex pharmaceutically interesting substrates, including examples for actual marketed drug compounds. Notably, this method constitutes a powerful tool for the generation of valuable internal standard materials for LC-MS/MS analyses highly demanded for various life-science applications.
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Strasse 29a, D-18059 Rostock, Germany.
Lorenz
L
Neubert
Dirk
D
Michalik
Sebastian
S
Bähn
Sebastian
S
Imm
Helfried
H
Neumann
Jens
J
Atzrodt
Volker
V
Derdau
Wolfgang
W
Holla
Matthias
M
Beller
D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D003903:Deuterium / Q000737:chemistry*; D041961:Deuterium Exchange Measurement; D006859:Hydrogen / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
D000588:Amines; D004364:Pharmaceutical Preparations; D012428:Ruthenium; D006859:Hydrogen; D003903:Deuterium