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

Abstract

Abstract:We have developed a novel and efficient iridium-catalyzed hydrogen isotope exchange (HIE) reaction method with secondary and tertiary sulphonamides at ambient temperatures. Furthermore N-oxides and phosphonamides have been successfully applied in HIE reactions with moderate to excellent deuterium introduction.

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

“…Thehigh sensitivity of the HIE reaction towards the steric properties of the amino acid enables an interesting selectivity towards glycine in different dipeptides,w hich can be tuned even by the choice of protecting group (Scheme 5). Dipeptides with N-terminal glycine are selectively labelled in the glycine position as long as acetyl is used as the protecting group (15,16). Thes teric demand of the C-terminal amino acid doesnti nfluence the deuterium yield strongly,a s demonstrated by an excellent 93 %i ncorporation observed for Ac-Gly-Tyr(OtBu)-OtBu (16).…”

Highlights of C (sp2)–H hydrogen isotope exchange reactions

“…In 2018, the Sanofi group reported further developments in the deuterium labelling of tertiary sulphonamides, quinolines, and phosphonamides using the Tamm catalyst as shown in Figure …”

C−H Functionalization—Prediction of Selectivity in Iridium(I)‐Catalyzed Hydrogen Isotope Exchange Competition Reactions

“…[7] Numerous HIE protocols utilizing homogeneous or heterogeneous catalysts have already been described. [2,8] Even though a new generation of bidentate iridium catalyst systems such as those from Pfaltz, [9] Burgess, [10] and Tamm [11] have extended the scope of the aromatic ortho-directing HIE reactions, (Scheme 1) the commercially available Crabtrees [12] and Kerrs catalyst [13,14] 1 remain the most regularly applied iridium catalysts in industry today. Interestingly new HIE applications have recently been published with great success utilizing other metals, such as iron, [15] cobalt, [16] or ruthenium, [17][18][19] or photoredox reactions [20] broadening the scope also to C(sp 3 )-carbon atoms.…”