Iridium catalyst systems of enhanced utility in hydrogen-isotope exchange

There exist a wide range of reported iridium catalysts which can facilitate hydrogen isotope exchange (HIE) upon aromatic compounds. Within this array, several catalysts stand out for their ability to mediate the HIE under mild conditions, with high levels of isotope incoporation.1 One key drawback in the labeling protocol with each catalyst is the necessity of an aromatic group to accept the isotopic label, limiting the utility to compounds containing functionalised aromatic skeletons. Our first effort to overcome this limitation was to apply nonaromatic unsaturated compounds, with skeletons related to the aromatic moieties previously labelled. However, each catalyst currently capable of HIE under mild conditions is also capable of olefin hydrogenation, typically under similar reaction conditions.2 In order to more effectively alleviate the appreciable issue of drug candidate attrition within medicinal chemistry research, isotopic labelling with heavy hydrogen (and other) isotopes is widely used as a means to monitor the fate of a potential drug molecule. In recent years, organoiridium complexes have garnered considerable attention within the field of transition metal-catalysed hydrogen-isotope exchange.1 Key to their applicability in this area is 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 (e.g. 1 → 2, Scheme 1).