Iridium-catalysed ortho-deuteration of primary sulfonamides : an experimental and computational study

Kerr, William and Reid, Marc and Tuttle, Christopher (2014) Iridium-catalysed ortho-deuteration of primary sulfonamides : an experimental and computational study. Journal of Labelled Compounds and Radiopharmaceuticals, 57 (3). pp. 183-184. ISSN 0362-4803 (https://doi.org/10.1002/jlcr.3173)

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Abstract

Isotopic labelling with heavy hydrogen isotopes (D2 and T2) is widely used as a means to monitor the biological fate of a potential drug molecule and represents a particularly industry-facing example of chemoselective organometallic catalysis. Consequently, preliminary studies from our laboratory have allowed expedient access to a series of novel iridium complexes, such as 2, that are able to catalyse the ortho-deuteration of various coordinating functionalities and pharmacophores, such as ketones, amides and nitro compounds 2 (Scheme 1). As part of our latest studies, we recently reported an efficient protocol for ortho-deuteration using more readily accessible Ir(I)chloro-carbene complexes. Turning to more challenging substrate classes, the utility of bench-stable catalysts such as 5 has now evolved to deliver the first highly effective strategy for the ortho-deuteration of primary sulfonamides at room temperature (Scheme 2). Additionally, we have used experimental and computational methods in parallel to explain the origins of observed chemoselectivity in labelling multi-functional drug molecules like 7, highlighting the importance of substrate–complex interactions during complexation. The details of all such studies will be delineated in this lecture.

ORCID iDs

Kerr, William ORCID logoORCID: https://orcid.org/0000-0002-1332-785X, Reid, Marc ORCID logoORCID: https://orcid.org/0000-0003-4394-3132 and Tuttle, Christopher;
CORE (COnnecting REpositories)