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

William J. Kerr, Gary J. Knox, Marc Reid, Tell Tuttle, Jonas Bergare, Ryan A. Bragg

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)11120–11126
Number of pages7
JournalACS Catalysis
Volume10
Issue number19
Early online date1 Sep 2020
DOIs
Publication statusPublished - 2 Oct 2020

Keywords

  • rational catalyst design
  • hydrogen isotope exchange
  • iridium catalysis
  • C–H activation
  • sulfone

Fingerprint Dive into the research topics of 'Computationally-guided development of a chelated NHC-P iridi-um(I) complex for the directed hydrogen isotope exchange of aryl sulfones'. Together they form a unique fingerprint.

Cite this