The Synthesis of Highly Active Iridium(I) Complexes and their Application in Catalytic Hydrogen Isotope Exchange

Abstract

This version is available at https://strathprints.strath.ac.uk/49161/ 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 Abstract. : A series of robust iridium(I) complexes bearing a sterically encumbered N-heterocyclic carbene ligand, alongside a phosphine ligand, has been synthesised and investigated in hydrogen isotope exchange processes. These complexes have allowed isotope incorporation over a range of substrates with the use of practically convenient deuterium and tritium gas. Moreover, these active catalysts are capable of isotope incorporation to particularly high levels, whilst employing low catalyst loadings and in short reaction times. In addition to this, these new catalyst species have shown flexible levels of chemoselectivity, which can be altered by simple manipulation of preparative approaches.Furthermore, a number of industrially-relevant drug molecules have also been labelled, including the sulfonamide containing drug, Celecoxib. Alongside detailed NMR experiments, initial mechanistic investigations have also been performed, providing insight into both substrate binding energies, and, more importantly, relative energies of key steps in the mechanistic cycle as part of the overall exchange process.

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity

“…As such, any studies which evaluate our developed catalysts in the labelling of aromatic esters should also compare them against the ability of 5 to mediate the same catalytic labelling reactions under identical conditions [19,29]. To this end, and to initiate this research programme, the labelling of a series of para-substituted ethyl benzoate derivatives 6 was examined, using our standard labelling protocol (5 mol % [Ir], 1 atm D2, 1 h) with Crabtree's catalyst 5 (Scheme 2, blue bars) and our developed catalyst systems 1b and 1a (Scheme 2, red and green bars, respectively).…”

Cobalt-Catalyzed Stereoretentive Hydrogen Isotope Exchange of C(sp3)–H Bonds

“…6 The most commonly used catalysts for HIE are homogeneous iridium complexes that typically rely on interaction with directing groups in the substrate to promote selective C(sp 2 )−H HIE. 7 Our laboratory recently reported a bis( N -heterocyclic-carbene)pyridine pincer iron-catalyst that exhibited highly predictable, sterically driven C(sp 2 )−H site selective HIE that is orthogonal to that observed with iridium (Scheme 1A). 8 …”

Efficient Water Reduction with sp3‐sp3 Diboron(4) Compounds: Application to Hydrogenations, H–D Exchange Reactions, and Carbonyl Reductions

“…[19] This methodology could be easily transferred to the developed conditions to obtain the stilbenes 30-32 (Scheme 4). [21] With this in hand, selective HDE was observed for the anticancer drug olaparib (33;64% deuterium incorporation), [21] With this in hand, selective HDE was observed for the anticancer drug olaparib (33;64% deuterium incorporation), …”