Photoredox-Catalyzed Cα -H Cyanation of Unactivated Secondary and Tertiary Aliphatic Amines: Late-Stage Functionalization and Mechanistic Studies

The Journal of Organic Chemistry
Ozgur YilmazMarion H Emmert

Abstract

This paper describes the development and mechanistic studies of a general, high-yielding amine Cα-H cyanation protocol via photoredox catalysis. Inexpensive NaCN is employed as the cyanide source and air is the external oxidant, resulting in mild and highly functional group tolerant conditions. Notably, efficient Cα-H cyanations of secondary and tertiary aliphatic amines and of complex, biologically active compounds (drugs) can be performed using the established methodology. Mechanistic studies suggest that the carboxylic acid additive has three effects: formation of a stabilizing hemiaminal intermediate, prevention of catalyst decomposition by protonating the substrate, and modulation of fluorescence quenching of the photoexcited catalyst species.

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Citations

Sep 12, 2019·Angewandte Chemie·Yueyue MaJinxing Ye
Dec 23, 2020·Chemical Society Reviews·Rolando CannalireMariateresa Giustiniano
Jan 20, 2021·The Journal of Organic Chemistry·Ozgur YilmazMarion H Emmert
Jun 5, 2021·Nature Communications·Fengjuan ChenWei Zeng
Dec 29, 2020·The Journal of Organic Chemistry·Martins S OderindeJames Kempson
Jan 14, 2020·Journal of the American Chemical Society·Martins S OderindeT G Murali Dhar
Sep 30, 2021·Chemical Reviews·Natalie Holmberg-Douglas, David A Nicewicz

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