Recent advances in iridium(I) catalysis towards directed hydrogen isotope exchange

Abstract

The initial discovery and establishment of a family of novel iridium catalysts possessing N-heterocyclic carbene units alongside bulky phosphine ligands allowed selected substrates to be labelled using deuterium or tritium gas at desirably low catalyst loadings via an ortho-directed C-H insertion process.Such a method has broad applicability and offers distinct advantages within the pharmaceutical industry, directly facilitating the ability to carefully monitor a potential drug molecule's biological fate. Over the past decade since these initial protocols were divulged, many additional advances have been made in terms of catalyst design and substrate scope. This review describes the broadened array of new iridium catalysts and associated protocols for direct and selective C-H activation and hydrogen isotope insertion within a number of new chemical entities of direct relevance to the pharmaceutical industry.

The Natural Product Lepidiline A as an N-Heterocyclic Carbene Ligand Precursor in Complexes of the Type [Ir(cod)(NHC)PPh3)]X: Synthesis, Characterisation, and Application in Hydrogen Isotope Exchange Catalysis

“…We envisaged that this naturally-occurring imidazolium salt could serve as a vehicle to begin to explore the effect of steric and electronic changes in the NHC on the activity of our Ir(I) NHC/phosphine catalysts [22]. Iridium(I) complexes are amongst the most effective metal catalysts for directed HIE [10] and, in recent years, we have introduced a suite of highly active Ir(I) catalysts bearing a combination of bulky phosphine and N-heterocyclic carbene ligands ( Figure 1). These catalysts are compatible with a broad variety of directing groups, enabling HIE on a wide range of substrates [11][12][13][14][15][16][17][18].…”

Nanocatalyzed Hydrogen Isotope Exchange

“…39 Since then, a plethora of iridium catalysts have been described for the homogeneous labelling of heterocycles and pharmaceuticals and some of them are commercially available as Kerr's or Burgess' catalysts. [40][41][42][43] These iridium catalysts are known to perform labelling in the ortho position of a directing group through 5-or 6-iridacycles and labelled compounds can be obtained with very high efficiency and regioselectivity. 44 However, despite the advantages of heterogeneous catalysis for multiple sites labelling and purification, iridium heterogeneous catalysts and nanoparticles are almost unseen in this field.…”

Copper-catalysed low-temperature water–gas shift reaction for selective deuteration of aryl halides

“… 5 However, practical procedures for deuteration with high quality control to produce isotopically pure compounds remain challenging. 6 Although C–H/C–D exchange (H/D exchange) reactions, are considered as the most convenient methods to produce D-labelled compounds, 7 alternative transformations such as dehalogenative deuterations are also essential components of the isotope labelling toolkit. Advantageously, dehalogenative deuteration can be easily controlled at specific positions and generally gives >99% D-incorporation.…”