C–H activation and hydrogen isotope exchange of aryl carbamates using iridium(I) complexes bearing chelating NHC-phosphine ligands

Zorzatto, Renan and Mulrainey, Paul T. and Reid, Marc and Tuttle, Tell and Lindsay, David M. and Kerr, William J. (2024) C–H activation and hydrogen isotope exchange of aryl carbamates using iridium(I) complexes bearing chelating NHC-phosphine ligands. Chemistry - A European Journal. e202403090. ISSN 1521-3765 (https://doi.org/10.1002/chem.202403090)

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Abstract

Hydrogen isotope exchange (HIE) via C–H activation constitutes an efficient method for the synthesis of isotopically-enriched compounds, which are crucial components of the drug discovery process and are extensively employed in mechanistic studies. A series of iridium(I) complexes, bearing a chelating phosphine-N-heterocyclic carbene ligand, was designed and synthesized for application in the catalytic HIE of challenging N- and O-aryl carbamates. A broad range of substrates were labeled efficiently, and applicability to biologically-relevant systems was demonstrated by labeling an ʟ-tyrosine-derived carbamate with excellent levels of deuterium incorporation. Combined theoretical and experimental studies unveiled intriguing mechanistic features within this process, in comparison to C–H activation and hydrogen isotope exchange catalysed by monodentate Ir(I) NHC/phosphine complexes.

ORCID iDs

Zorzatto, Renan ORCID logoORCID: https://orcid.org/0000-0002-6923-7837, Mulrainey, Paul T., Reid, Marc ORCID logoORCID: https://orcid.org/0000-0003-4394-3132, Tuttle, Tell, Lindsay, David M. ORCID logoORCID: https://orcid.org/0000-0003-4498-5094 and Kerr, William J. ORCID logoORCID: https://orcid.org/0000-0002-1332-785X;
CORE (COnnecting REpositories)