Nickel-catalysed deuteration of benzylic C(sp3)–H bonds using D2O

Hydrogen isotope exchange, which can directly introduce deuterium without the need to pre-functionalize starting materials and without substantially altering the structure of molecules, is the most efficient method for deuterium incorporation. Here we present a heterogeneous nickel-catalysed deuteration of benzylic positions in alkylarenes and methylarenes using D2O as a deuterium source. For this transformation, we developed a Ni–H2–D2O system that enables H–D exchange of benzylic positions. A nitrogen-containing precursor has a substantial influence on the particle size of the nickel nanoparticles and volcano-type curves concerning the activity in the catalyst. This H–D exchange reaction shows broad substrate scope and good functional group tolerance. Deuterated building blocks, including representative drugs with high deuterium incorporation, were obtained using inexpensive and easy-to-handle D2O. Mechanistic studies indicated that H2 was essential for the isotope exchange process. We envision that such metal–H2–D2O systems could be applied in more catalytic reactions for the preparation of deuterium-labelled compounds. A heterogeneous nickel-catalysed deuteration reaction of benzylic C(sp3)–H bonds in alkylarenes and methylarenes using D2O is developed. Such metal–H2–D2O systems could be extended to other catalytic reactions for the preparation of deuterium-labelled compounds in the future.