Iridium-catalyzed C-H activation and deuteration of primary sulfonamides : an experimental and computational study

Kerr, William J. and Reid, Marc and Tuttle, Tell (2015) Iridium-catalyzed C-H activation and deuteration of primary sulfonamides : an experimental and computational study. ACS Catalysis, 5 (1). 402–410. ISSN 2155-5435

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    Abstract

    Iridium-catalyzed C-H activation and ortho-hydrogen isotope exchange is an important technology for allowing access to labelled organic substrates and aromatic drug molecules, and for the development of further C-H activation processes in organic synthesis. The use of [(COD)Ir(NHC)Cl] complexes (NHC = N-heterocyclic carbene) in the ortho-deuteration of primary sulfonamides under ambient conditions is reported. This methodology has been applied to the deuteration of a series of substrates, including the COX-2 inhibitors Celecoxib and Mavacoxib, demonstrating selective complexation of the primary sulfonamide over a competing pyrazole moiety. The observed chemoselectivity can be reversed by employing more encumbered catalyst derivatives of the type [(COD)Ir(NHC)(PPh3)]PF6. Computational studies have revealed that, although C-H activation is rate-determining, substrate complexation or subsequent C-H activation can be product-determining depending on the catalyst employed.