Regioselective deuterium labelling of aromatic acids, amides and amines using group VIII metal catalysts

Abstract

SUMMARYOrtho-deuterated arylcarboxylic acids and their sodium salts may be prepared with high regioselectivity by isotopic exchange with deuterium oxide in the presence of a range of commercially available group VIII metal complexes. When rhodium trichloride trihydrate is employed a range of arylcarboxamides and arylmethanamines are also selectively labelled at the ortho-positions.

Tritium: a coming of age for drug discovery and development ADME studies

“…The catalyst for this process is usually an Ir or Rh complex bearing suitable ligands. For tritiated water exchanges, the catalyst is usually either triaquotrichlororhodium(III), RhCl 3 ·3H 2 O, or a suitable cyclooctadienyl iridium(I) dionate such as (4) …”

C−H Functionalisation for Hydrogen Isotope Exchange

“…The rich history of homogeneous Rh-catalyzed hydrogen isotope exchange [ 131 , 132 , 133 , 134 , 135 , 136 , 137 ] has continued to evolve over the last decade. The principles of directed HIE originally developed by Lockley, Hesk, and Jones [132,133,134,135,136] have been applied by Li and co-workers using a bisphosphine, chelation-assisted Rh(III) catalyst series, led by 135, in the directed labeling of various N-heterocycles (136→137; Scheme 42). [138] The catalyst structure was optimized by simple screening of available phosphine ligands.…”

“…The RhCl3 catalyst was used as a precursor to an active species with complementary reactivity to that previously divulged by Lockley. [132,133,134] More specifically, the bis(3,5dimethylpyrazol-1-yl) acetate (bdmpza) ligand, 141, delivered an anionic Rh(III)-centred pre-catalyst, 142, that was able to deuterate both aryl and β-alkyl positions of substrates bearing no strong directing group (143→143a; Scheme 43). [139] Under identical conditions, the parent RhCl3.H2O was more selective for aryl deuteration (143→143b).…”

Methoden der C‐H‐Funktionalisierung für den Wasserstoffisotopenaustausch

“…The rich history of homogeneous Rh-catalyzed hydrogen isotope exchange [ 131 , 132 , 133 , 134 , 135 , 136 , 137 ] has continued to evolve over the last decade. The principles of directed HIE originally developed by Lockley, Hesk, and Jones [132,133,134,135,136] have been applied by Li and co-workers using a bisphosphine, chelation-assisted Rh(III) catalyst series, led by 135, in the directed labeling of various N-heterocycles (136→137; Scheme 42). [138] The catalyst structure was optimized by simple screening of available phosphine ligands.…”