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

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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.