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

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 63; no. 6; pp. 281 - 295
• Main Authors: Kerr, William J., Knox, Gary J., Paterson, Laura C.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 30.05.2020
• Subjects: Catalysis; Catalysts; deuteration; Deuterium; Deuterium - chemistry; Deuterium Exchange Measurement; Hydrogen - chemistry; hydrogen isotope exchange; Hydrogen isotopes; Insertion; iridium; Iridium - chemistry; Iridium network; N‐heterocyclic carbene; Pharmaceutical industry; Pharmaceuticals; Phosphine; Phosphines; Substrates; tritiation; Tritium; N-heterocyclic carbene; iridium; deuteration; tritiation; hydrogen isotope exchange
• ISSN: 0362-4803; 1099-1344; 1099-1344
• DOI: 10.1002/jlcr.3812

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.