Isotopic Labelling of Functionalised Arenes Catalysed by Iridium(I) Species of the [(cod)Ir(NHC)(py)]PF6 Complex Class

Abstract

0035-1560518This version is available at https://strathprints.strath.ac.uk/54692/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. Abstract Ir(I) complexes of the type [(COD)Ir(NHC)(Py)]PF6 have been exposed as efficient catalysts in the area of hydrogen isotope exchange. More specifically, via an ortho-directed C-H activation process, high levels of deuterium incorporation have been achieved using low levels of catalyst over a range of functionalised aromatic compounds. Additionally, the developed protocol has been extended to include a selected pharmacological target, where chemoselective labelling is observed within such a multifunctional substrate. Key words iridium, C-H activation, hydrogen isotope exchange, deuterationIsotopic labelling with heavy hydrogen isotopes (D2 and T2) is widely used as a means to monitor the biological fate of a potential drug molecule. 2 In relation to this, methods that deliver hydrogen isotope exchange (HIE) are of appreciable importance in accessing such isotopically-labelled species, whilst also being central to the provision of analogous deuterated compounds for use as internal standards as aligned with mass spectrometry, 3 for kinetic isotope studies, 4 and for the alteration of reaction pathways in total synthesis. 5 As such, direct, flexible, and selective means of introducing hydrogen isotopes continues to be the focus of considerable research attention. In this regard, studies from our laboratory have shown that a range of iridium complexes of the type [(COD)Ir(IMes)(PR3)]X are very effective homogeneous catalysts which mediate the exchange of hydrogen with deuterium (or tritium) via an ortho-directed C-H activation process. 2c,6 The key to their applicability in this area lies with the ability of such complexes to selectively target unactivated C-H bonds, whilst simultaneously allowing convenient isotope incorporation with the use of, practically convenient, deuterium or tritium gas (Sc...

Advances in the Synthesis and Applications of N-Heterocyclic Carbene Metal Complexes with a Focus on the Weak Base Route

“… The [Ir­(ICy)­(cod)­(py)]­PF 6 complex has shown the highest catalytic activity in transfer hydrogenation of ketones and moderate activity toward simple olefins and 2,6-dimethylnitrobenzene. The same complexes were studied in 2016 by Kerr as catalysts for isotopic labeling of functionalized arenes, where SIMes was reported as the best-performing catalyst . The yields of the iridium complexes obtained from the free carbene route are summarized in Table .…”

“…The same complexes were studied in 2016 by Kerr as catalysts for isotopic labeling of functionalized arenes, where SIMes was reported as the best-performing catalyst. 71 The yields of the iridium complexes obtained from the free carbene route are summarized in Table 14.…”

Photo- and electro-catalytic deuteration of feedstock chemicals and pharmaceuticals: A review

“…Recently, great efforts are devoted to the development of HIE strategies with site selectivity using metal catalysts for developing effective diagnostics for ADME studies [16]. The most widely used metal catalysts for isotopic site-selective HIE are Ir(I) complexes developed by Crabtree and Kerr [17][18][19][20]; they enable ortho exchange in the presence of directing groups. Nevertheless, conventional HIEs generally suffer from drawbacks such as the requirement of harsh conditions (e.g., strong acids/bases, high temperature, and flammable gases) and/or multi-exchange processes to ensure high degree of deuterium incorporation.…”

Hydro/Deutero Deamination of Arylazo Sulfones under Metal- and (Photo)Catalyst-Free Conditions

“…Concerning the formation of an Ar–D bond, various processes has been reported based on the activation of an Ar–H [10] or an Ar–X bond. In the former case, the C–H activation of arenes may occur under Pd- [11], Fe- [12], Rh- [13] (in the presence of deuterated acetic or trifluoroacetic acids as the deuterating agents), Ru- [14] and Ir- [15,16] catalysis (D 2 was used as the deuteron source, see Scheme 1a). Acid/base-mediated labeling strategies making use of D 2 O as a rather inexpensive deuteron source were also proposed [17,18].…”