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

Abstract

Fort he first time,w ed escribe highly selective homogeneous iridium-catalyzed hydrogen isotope exchange (HIE) of unactivated C(sp 3 )centers in aliphatic amides.When using the commercially available Kerr catalyst, the HIE with as eries of common antibody-drug conjugate (ADC) linker side chains proceeds with high yields,high regioselectivity,and with deuterium incorporation up to 99 %. The method is fully translatable to the specific requirements of tritium chemistry and its effectiveness was demonstrated by direct tritium labelling of am aytansinoid. The scope of the method can be extended to simple amino acids,w ith high HIE activity observed for glycine and alanine.I nd i-and tripeptides, avery interesting protecting-group-dependent tunable selectivity was observed. DFT calculations gave insight into the energies of the transition states,therebyexplaining the observed selectivity and the influence of the amino acid protecting groups.

Chemoselective Alpha‐Deuteration of Amides via Retro‐ene Reaction

“…Recently, Atzrodt and Derdau described an iridium‐catalyzed deuteration of aliphatic amides using gaseous D 2 that was even applicable to small peptides (Scheme 1 C). [33] …”

Method Development and Syntheses Examples of Isotopically Labeled Compounds to Foster Operational Excellence in Pharma Industry

“…However, the use of 50 mol% catalyst like in this case is an exception, normally the reactions are optimized to apply 2–10 mol% catalyst. 18…”

Oxygen vacancy of CeO2 modulated Pt catalyst facilitates H‐D exchange of aniline aromatics by cleaving D2O

“…Consequently, to meet the demand for deuterium‐labeled compounds, new and versatile deuterium labeling methods are actively being explored 19–23 . A direct and commonly employed method is through hydrogen isotope exchange (HIE) facilitated by catalysts 24–29 . Numerous approaches have been documented for aniline deuteration.…”

“…[19][20][21][22][23] A direct and commonly employed method is through hydrogen isotope exchange (HIE) facilitated by catalysts. [24][25][26][27][28][29] Numerous approaches have been documented for aniline deuteration. However, it is important to consider side reactions such as hydrogenation of the benzene ring during the reaction process.…”