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

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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.

ORCID iDs

Kerr, William J. ORCID logoORCID: https://orcid.org/0000-0002-1332-785X, Knox, Gary J. ORCID logoORCID: https://orcid.org/0000-0003-2674-9338, Reid, Marc ORCID logoORCID: https://orcid.org/0000-0003-4394-3132, Tuttle, Tell, Bergare, Jonas and Bragg, Ryan A.;
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