Selective α‐Deuteration of Cinnamonitriles using D2O as Deuterium Source. Issue 1 (8th October 2021)

• Record Type: Journal Article
• Authors: Guo, Beibei; de Vries, Johannes G.; Otten, Edwin
• Is Part Of: Advanced synthesis & catalysis. Volume 364:Issue 1(2022)
• Page Start: 179
• Page End: 186
• Publication Date: 2021-10-08
• Subjects: homogeneous catalysis -- deuterium -- metal-ligand cooperation -- unsaturated nitriles; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.202101093
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: The selective α‐deuteration of α, β‐unsaturated nitriles using the strong base t BuOK or a metal‐ligand cooperative Ru pincer catalyst is described. With D2 O as deuterium source and glyme as solvent at 70 °C, t BuOK 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 t BuOK‐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 t BuOK, 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 t BuOK as catalyst, whereas H/D exchange catalysis with the Ru PNN pincer likely proceeds via (reversible) oxa‐Michael addition of D2 O. Abstract :