Burgess iridium(I)-catalyst for selective hydrogen isotope exchange

Abstract

We have evaluated the commercially available Burgess catalyst in hydrogen isotope exchange reactions with several substrates bearing different directing group functionalities and have obtained moderate to high (50%-97%D) deuterium incorporations. The broad applicability in hydrogen isotope exchange reactions makes the Burgess catalyst a possible alternative compared to other commercially available iridium(I)-catalysts.

Evaluation of a P,N‐ligated iridium(I) catalyst in hydrogen isotope exchange reactions of aryl and heteroaryl compounds

“…With this catalyst, we have developed the first practical HIE protocol for selective ortho-deuteration of various secondary and tertiary sulfonamides as well as sulfonyl ureas. 37,38 A similar reactivity was also observed for monodentate Kerr catalysts of the type 39 [(COD)Ir(NHC)Cl] (3), which proved even more efficient in the HIE reaction of secondary sulfonamides and ureas, while 5 resulted in greater deuterium incorporation for tertiary sulfonamides. 37 This method was also applied to sulfo drugs and even adopted to the special conditions required for selective tritium labelling (5-10 eq.…”

“…In the case of the primary sulfonamide 8 , catalyst 6 showed similar degree of deuteration incorporation as compared to the results reported by Kerr with catalyst 3 at room temperature, however with a higher amount of catalyst (10 mol%) . Interestingly, secondary ( 9‐11 ) and tertiary ( 12‐15 ) sulfonamides underwent successful HIE reactions with 6 at room temperature as well, which was achieved previously with catalysts 3 and 5 only at elevated temperatures (>80–120°C) …”

“…Based on a comprehensive screening of readily available Ir‐catalysts, we recently identified another hydrogenation catalyst to have also an appreciable HIE capacity, viz, the commercial, air‐stable Burgess catalyst 5 . With this catalyst, we have developed the first practical HIE protocol for selective ortho ‐deuteration of various secondary and tertiary sulfonamides as well as sulfonyl ureas . A similar reactivity was also observed for monodentate Kerr catalysts of the type [(COD)Ir(NHC)Cl] ( 3 ), which proved even more efficient in the HIE reaction of secondary sulfonamides and ureas, while 5 resulted in greater deuterium incorporation for tertiary sulfonamides .…”

“…of T 2 gas, low pressure). However, the elevated temperatures of 100 to 120°C required to obtain reasonable deuterium incorporation still remains an important limitation of this method …”

Highly Selective Directed Iridium‐Catalyzed Hydrogen Isotope Exchange Reactions of Aliphatic Amides

“…[7,8] Numerous HIE methods based on homogeneous or heterogeneous catalysis have already been described. [1,2,9] Recent research has strongly focused on selective ortho-directed HIE reactions of aromatic substrates based on homogeneous iridium(I) complexes,with the commercial Crabtreescatalyst [10] and Kerrscatalyst [11,12] (1)b eing the most prominent catalysts applied today.E ven though anew generation of bidentate catalyst systems such as those from the groups of Pfaltz, [13] Burgess, [14] and Tamm [15] have extended the scope of aromatic ortho-directing HIE (Scheme 1), this is still restricted to C(sp 2 )carbons.…”