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Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones.

ABSTRACT: Herein, we report the rational, computationally-guided design of an iridium(I) catalyst system capable of enabling directed hydrogen isotope exchange (HIE) with the challenging sulfone directing group. Substrate binding energy was used as a parameter 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 catalyst is maintained at low pressures of deuterium gas and apply these conditions to tritium radiolabeling, including the expedient synthesis of a tritium-labeled drug molecule.

SUBMITTER: Kerr WJ

PROVIDER: S-EPMC7587147 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones.

Kerr William J WJ Knox Gary J GJ Reid Marc M Tuttle Tell T Bergare Jonas J Bragg Ryan A RA

ACS catalysis 20200901 19

Herein, we report the rational, computationally-guided design of an iridium(I) catalyst system capable of enabling directed hydrogen isotope exchange (HIE) with the challenging sulfone directing group. Substrate binding energy was used as a parameter to guide rational ligand design via an <i>in silico</i> 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 ...[more]

PMID: 33123410

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