Palladium Nanoparticles for the Deuteration and Tritiation of Benzylic Positions on Complex Molecules

Abstract

Palladium nanoparticles (PdNp) were revealed as an efficient hydrogen isotope exchange catalyst for the deuterium and tritium labeling of benzylic positions of complex molecules. A practical way to obtain small palladium nanoparticles and to apply them as a catalyst for hydrogen isotope exchange (HIE) is presented. Several model compounds and popular bioactive molecules were submitted to HIE reactions catalyzed by the PdNp. Benzylic positions situated far away from heteroatoms were labeled with high isotopic enrichments. The observed non-directed HIE gave rise to regioselectivities complementary to those obtained with other methods, which typically require specific directing groups. For this reason, the successful deuteration of a broad variety of benzylic positions created a helpful tool to produce internal LC-MS standards of complex drugs. Furthermore, this nanocatalyst paved the way for the radiolabeling of drug molecules with high specific activities by using low pressures of tritium gas.

Keywords: C−H activation; benzylic positions; hydrogen isotope exchange; internal standards; metal nanoparticles.