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.
Original language | English |
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Pages (from-to) | 402–410 |
Number of pages | 9 |
Journal | ACS Catalysis |
Volume | 5 |
Issue number | 1 |
Early online date | 2 Dec 2014 |
DOIs | |
Publication status | Published - 2 Jan 2015 |
Keywords
- iridium
- C-H activation
- ortho-deuteration
- hydrogen-isotope exchange
- sulfonamide