Selective α-Deuteration of Cinnamonitriles using D2O as Deuterium Source

Beibei Guo, Johannes G. de Vries*, Edwin Otten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

The selective α-deuteration of α,β-unsaturated nitriles using the strong base tBuOK or a metal-ligand cooperative Ru pincer catalyst is described. With D2O as deuterium source and glyme as solvent at 70 °C, tBuOK is an efficient catalyst for deuteration at the α-C(sp 2) position of cinnamonitriles, providing access to a broad range of deuterated derivatives in good to excellent yields and with very high levels of deuterium incorporation. While the tBuOK-catalysed protocol does not tolerate base-sensitive functional groups, cinnamonitrile derivatives containing a benzylic bromide or ester moiety were deuterated in excellent yields using Milstein's ruthenium PNN pincer catalyst. Moreover, the activity for H/D exchange of the metal-ligand cooperative Ru catalyst is found to be significantly higher than that of tBuOK, allowing reactions to proceed well even at room temperature. A mechanistic proposal is put forward that involves deprotonation of the cinnamonitrile α-CH position when using tBuOK as catalyst, whereas H/D exchange catalysis with the Ru PNN pincer likely proceeds via (reversible) oxa-Michael addition of D2O.

Original languageEnglish
Pages (from-to)179-186
Number of pages8
JournalAdvanced Synthesis and Catalysis
Volume364
Issue number1
Early online date27-Sept-2021
DOIs
Publication statusPublished - 4-Jan-2022

Keywords

  • homogeneous catalysis
  • deuterium
  • metal-ligand cooperation
  • unsaturated nitriles

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