Practically convenient and industrially-aligned methods for iridium-catalysed hydrogen isotope exchange processes

Abstract

The use of alternative solvents in the iridium-catalysed hydrogen isotope exchange reaction with developing phosphine/NHC Ir(I) complexes has identified reaction media which are more widely applicable and industrially acceptable than the commonly employed chlorinated solvent, dichloromethane. Deuterium incorporation into a variety of substrates has proceeded to deliver high levels of labelling (and regioselectivity) in the presence of low catalyst loadings and over short reaction times. The preparative outputs have been complemented by DFT studies to explore ligand orientation, as well as solvent and substrate binding energies within the catalyst system.

The Synthesis of Highly Active Iridium(I) Complexes and their Application in Catalytic Hydrogen Isotope Exchange

“…[22] The stabilisation energy, ∆H bind , resulting from the complexation of the substrate to the iridium metal, forming the species akin to 16, is calculated as the difference in enthalpy between the enthalpy of the optimised complex, 16, and the sum of the enthalpies of the optimised substrate and the optimised [(D 2 )Ir(PMe 3 )(NHC)] + complex. As illustrated by the values in Table 7, all complexes have a stabilising interaction enthalpy with the substrates.…”

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity

“…Over recent years, research in our laboratory has focused on the development of iridium(I) N-heterocyclic carbene (NHC)-ligated precatalysts of the type 1, and their application in HIE via ortho-directed C-H activation protocols (2→4 via 3, Scheme 1) [6,[16][17][18][19][20][21][22]. Despite the growing list of compatible directing groups, we [23] and others [24][25][26][27] have found these developed C-H activation methods less applicable in the labelling of aromatic esters under ambient conditions.…”

Ionic Liquids: Recent Advances and Applications in Boron Chemistry

“…Isotope labelling of chemicals has broad applications in the pharmaceutical and fine chemicals industries . For example, deuterium‐labeled compounds such as D 2 O, C 6 D 6 , and CDCl 3 can be used as solvents in NMR spectroscopy, in labeled drugs, and as probes in mass spectrometry .…”

“…Isotope labelling of chemicals has broad applications in the pharmaceutical and fine chemicals industries . For example, deuterium‐labeled compounds such as D 2 O, C 6 D 6 , and CDCl 3 can be used as solvents in NMR spectroscopy, in labeled drugs, and as probes in mass spectrometry . Isotope‐labeled chemicals can be synthesized either by using the appropriately labeled substrates or by a catalytic isotope exchange process .…”

“…For example, deuterium‐labeled compounds such as D 2 O, C 6 D 6 , and CDCl 3 can be used as solvents in NMR spectroscopy, in labeled drugs, and as probes in mass spectrometry . Isotope‐labeled chemicals can be synthesized either by using the appropriately labeled substrates or by a catalytic isotope exchange process . Deuterated alcohols can be prepared by reduction of the corresponding aldehydes or ketones with deuterated reagents such as NaBD 4 and LiAlD 4 , .…”