Computationally-guided development of a chelated NHC-P iridium(I) complex for the directed hydrogen isotope exchange of aryl sulfones

Kerr, William J. and Knox, Gary J. and Reid, Marc and Tuttle, Tell and Bergare, Jonas and Bragg, Ryan A. (2020) Computationally-guided development of a chelated NHC-P iridium(I) complex for the directed hydrogen isotope exchange of aryl sulfones. ACS Catalysis, 10 (19). pp. 11120-11126. ISSN 2155-5435 (https://doi.org/10.1021/acscatal.0c03031)

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Abstract

Herein we report the rational, computationally-guided design of an iridium(I) catalyst system capable of enabling directed hy-drogen isotope exchange (HIE) with the challenging sulfone directing group. Substrate binding energy was used as a parame-ter to guide rational ligand design via an in-silico catalyst screen, resulting in a lead series of chelated iridium(I) NHC-phosphine complexes. Subsequent preparative studies show that the optimal catalyst system displays high levels of activity in HIE, and we demonstrate the labeling of a broad scope of substituted aryl sulfones. We also show that the activity of the cata-lyst is maintained at low pressures of deuterium gas, and apply these conditions to tritium radiolabeling, including the expedi-ent synthesis of a tritium-labeled drug molecule.

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