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Directed Iridium‐Catalyzed Hydrogen Isotope Exchange Reactions of Phenylacetic Acid Esters and Amides
Author(s) -
Valero Mégane,
Becker Daniel,
Jess Kristof,
Weck Remo,
Atzrodt Jens,
Bannenberg Thomas,
Derdau Volker,
Tamm Matthias
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201901449
Subject(s) - phenylacetic acid , iridium , chemistry , catalysis , phosphine , imine , ligand (biochemistry) , homogeneous catalysis , organic chemistry , medicinal chemistry , combinatorial chemistry , biochemistry , receptor
For the first time, a catalytic protocol for a highly selective hydrogen isotope exchange (HIE) of phenylacetic acid esters and amides under very mild reaction conditions is reported. Using a homogeneous iridium catalyst supported by a bidentate phosphine‐imidazolin‐2‐imine P,N ligand, the HIE reaction on a series of phenylacetic acid derivatives proceeds with high yields, high selectivity, and with deuterium incorporation up to 99 %. The method is fully adaptable to the specific requirements of tritium chemistry, and its effectiveness was demonstrated by direct tritium labeling of the fungicide benalaxyl and the drug camylofine. Further insights into the mechanism of the HIE reaction with catalyst 1 have been provided utilizing DFT calculations, NMR studies, and X‐ray diffraction analysis.