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.Apractical waytoobtain small palladium nanoparticles and to apply them as acatalyst for hydrogen isotope exchange (HIE) is presented. Several model compounds and popular bioactive molecules were submitted to HIE reactions catalyzed by the PdNp.B enzylic positions situated far away from heteroatoms were labeled with high isotopic enrichments.T he observed non-directed HIE gave rise to regioselectivities complementary to those obtained with other methods,w hich typically require specific directing groups.F or this reason, the successful deuteration of abroad variety of benzylic positions created ahelpful tool to produce internal LC-MS standards of complex drugs.F urthermore,t his nanocatalyst paved the way for the radiolabeling of drug molecules with high specific activities by using low pressures of tritium gas.

Rhodium‐Catalyzed Stereoselective Deuteration of Benzylic C–H Bonds via Reversible η6‐Coordination

“…Chirik reported a notable cobalt‐catalyzed benzylic H/D exchange of alkylarenes with D 2 gas, [9] however, the functional group compatibility remains to be explored. During the preparation of this manuscript, Pfeifer developed a Pd nanoparticles catalyzed benzylic HIE with D 2 or T 2 , which works well for the deuteration and tritiation of complex molecules [10] . Given the large number of pharmaceuticals with aromatic rings, the development of new strategies for benzylic H/D exchange, that use a convenient deuterium source and are applicable to a broad range of molecules would be attractive especially with homogeneous catalysis.…”

Cesium Amide‐Catalyzed Selective Deuteration of Benzylic C‐H Bonds with D2 and Application for Tritiation of Pharmaceuticals

“…Chirik in 2017 reported the selective deuteration of benzylic C−H bonds with D 2 by a cobalt catalyst (Scheme 1B1) [14] . Very recently, Pfeifer developed PVP‐stabilized palladium nanoparticles as efficient catalyst for the selective deuteration and tritiation of benzylic positions on various model substrates and pharmaceutical compounds in presence of D 2 or T 2 (Scheme 1B2) [15] . Base catalysts are traditionally known for tritiation of acidic C−H bonds with diluted tritiated water but generally gave low tritium enrichments.…”

Homogenous Iron-Catalysed Deuteration of Electron-Rich Arenes and Heteroarenes

“…Similarly, photocatalytic 14 and electrocatalytic 15 labelling reactions are on the rise. In addition, the use of supported catalysts becomes important in the field of HIE, with reports utilising ruthenium, 16 iridium, 17 palladium, 18 rhodium, 19 iron, 20 and manganese 21 nanoparticles. Another trend in HIE reactions is the use of frustrated Lewis pairs (FLP) and Lewis acids (LA) for the incorporation of deuterium atoms in electron-rich arenes and heteroarenes.…”