Hydrogen Isotope Exchange with Iridium(I) Complexes Supported by Phosphine‐Imidazolin‐2‐imine P,N Ligands

Abstract

Phenylene-bridged hybrid phosphine-imidazolin-2-imine R P, N R' ligands (R = Ph, Cy, i-Pr, t-Bu; R' = Me, i-Pr) were preparedf rom 1,2-dibromobenzene by palladium-catalyzed C-N coupling with 1,3,4,5-tetramethylimidazolin-2-imine or 1,3-diisopropyl-4,5-dimethylimidazolin-2-imine,f ollowed by lithiation with tert-butyllithium andr eactionw ith the chlorophosphines( R 2 PCl). Their reactionw ith the dimeric iridium complex [Ir(cod)Cl] 2 (cod = 1,5-cyclooctadiene) ands ubsequent anione xchange with sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBArF 24 )o rp otassium hexafluorophosphate (KPF 6 )a ffordedi ridium complexes of the type [( R P, N R' )Ir(cod)]BArF 24 or [( R P, N R' )Ir(cod)]PF 6 ,r espectively.T he latter PF 6 salts were structurallyc har-acterized, revealing shortI r-N bonds as an indication of electron-rich nitrogen donor atoms.T he former complexes were tested for theira pplicability in catalytic H/De xchange.I np articular,t he complex with the ligand t-Bu P, N Me showedr emarkable performance in H/D exchange with ab road range of aromatic substrates,i ncluding ketones,a mides,e sters, heterocycles and nitro compounds, and also promoted H/De xchange at aromaticB oc-protected amines, benzylamines and methoxy derivatives.

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

“…sulfonamides . Another new class of bidentate iridium(I)‐catalysts with phenylene‐bridged hybrid phosphine‐imidazolin‐2‐imine P,N ligands has been recently introduced by Tamm . Tamm's catalyst 5 showed remarkable performance with a broad range of known directing groups and even promoted selective H/D exchange at aromatic Boc‐protected amines, benzyl amines, and methoxy derivatives, which had not been recognized previously as directing groups for ortho selective HIE …”

Tritiation of azido‐labeled diiodo cabazitaxel (Jevtana) and docetaxel (Taxotere) derivatives to generate 3H‐photoaffinity probes

“…Unfortunately, both the commercially available Crabtree‐ and Kerr‐ catalysts as well as high temperature solid state isotopic exchange resulted in specific activities less than 10 Ci/mmol. While this may be sufficient for most pharmacokinetic studies, for our labelling experiments, we required a specific activity of at least 50 Ci/mmol …”

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

“…In addition to the high HIE reactivity for known directing groups such as acetyl, heterocycles, sulfones, nitro groups, and benzyl amines, 6 proved to be also highly active for H/D exchange of Boc‐protected anilines, which had not been recognized previously as a directing group for HIE. After optimization, even substrates with the weakly coordinating methoxy group showed a good degree of deuteration . In continuous efforts to broaden our synthetic repertoire for fast tritium labelling, we have further investigated the substrate scope of 6 in more detail and wish to report on expanded applications of the new catalyst system 6 .…”

“…General: All substrates and solvents were obtained from commercial suppliers and used without further purification, except for the phosphonamides 23 to 27 (the preparation is described in the Supporting Information). Catalyst 6 was synthesized according to procedures reported earlier . All labelling reactions were performed on Radleys Synthesis station for parallel solution phase chemistry.…”