Ruthenium-Catalyzed Deuteration of Aromatic Carbonyl Compounds with a Catalytic Transient Directing Group

Sara Kopf, Fei Ye, Helfried Neumann, Matthias Beller

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

A novel ruthenium-catalyzed C−H activation methodology for hydrogen isotope exchange of aromatic carbonyl compounds is presented. In the presence of catalytic amounts of specific amine additives, a transient directing group is formed in situ, which directs selective deuteration. A high degree of deuteration is achieved for α-carbonyl and aromatic ortho-positions. In addition, appropriate choice of conditions allows for exclusive labeling of the α-carbonyl position while a procedure for the preparation of merely ortho-deuterated compounds is also reported. This methodology proceeds with good functional group tolerance and can be also applied for deuteration of pharmaceutical drugs. Mechanistic studies reveal a kinetic isotope effect of 2.2, showing that the C−H activation is likely the rate-determining step of the catalytic cycle. Using deuterium oxide as a cheap and convenient source of deuterium, the methodology presents a cost-efficient alternative to state-of-the-art iridium-catalyzed procedures.

Original languageEnglish
Pages (from-to)9768-9773
Number of pages6
JournalChemistry - A European Journal
Volume27
Issue number38
DOIs
StatePublished - 7 Jul 2021
Externally publishedYes

Keywords

  • C−H activation
  • hydrogen isotope exchange
  • ketones
  • ruthenium
  • transient directing group

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