Deuteration of Arenes via Pd-Catalyzed C-H Activation: A Lesson in Nondirected C-H Activation, Isotopic Labeling, and NMR Characterization.

Abstract

Isotopic labeling is an important tool in medicinal research, metabolomics, and for understanding reaction mechanisms. In this context, transition metal-catalyzed C-H activation has emerged as a key technology for deuterium incorporation via hydrogen isotope exchange. A detailed and easy-to-implement experimental procedure for a nondirected arene deuteration has been developed that exclusively uses commercial equipment and chemicals. The protocol is ideally suited for students and other prospective applicants who are not experts in catalysis. The degree of deuterium incorporation was analyzed via different means like mass spectrometry and 1H and 2H nuclear magnetic resonance (NMR). A hands-on understanding of quantitative NMR, as well as the influence of H/D exchange on experimental spectra, was conveyed by comparative NMR spin simulations. Students were measurably familiarized with the concepts of C-H activation, isotope effects, and basics in experimental catalysis.