Selective α-Deuteration of Cinnamonitriles using D₂O as Deuterium Source

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.