Photoredox-Catalyzed Enantioselective α-Deuteration of Azaarenes with D2O
Tianju Shao,
Yajuan Li,
Nana Ma,
Chunyang Li,
Guobi Chai,
Xiaowei Zhao,
Baokun Qiao,
Zhiyong Jiang
Affiliations
Tianju Shao
Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Kaifeng, Henan 475004, P. R. China
Yajuan Li
Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Kaifeng, Henan 475004, P. R. China
Nana Ma
Henan Key Laboratory of Organic Functional Molecules and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China
Chunyang Li
Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Kaifeng, Henan 475004, P. R. China
Guobi Chai
Zhengzhou Tobacco Research of CNTC, Zhengzhou, Henan 450001, P. R. China
Xiaowei Zhao
Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Kaifeng, Henan 475004, P. R. China
Baokun Qiao
Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Kaifeng, Henan 475004, P. R. China; Corresponding author
Zhiyong Jiang
Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Kaifeng, Henan 475004, P. R. China; Henan Key Laboratory of Organic Functional Molecules and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China; Corresponding author
Summary: The site-specific incorporation of deuterium (D) into small molecules is frequently used to access isotopically labeled compounds with broad utility in many research areas, such as drug development, mechanistic studies, and NMR analyses. Nevertheless, the deuteration of a stereocenter in an enantioselective manner, which could slow the metabolism and improve the bioavailability of bioactive molecules, remains challenging owing to the lack of established catalytic methods. Here, we report an asymmetric α-deuteration strategy for azaarenes with inexpensive D2O as the deuterium source. A cooperative visible light-driven photoredox and chiral Brønsted acid–catalyzed system using a Hantzsch ester as the terminal reductant has been developed, which enables racemic α-chloro-azaarenes and prochiral azaarene-substituted ketones to experience a single-electron reduction–enantioselective deuteration process. The transition metal-free method provides important chiral α-deuterated azaarenes in satisfactory yields with good to excellent enantioselectivities (up to 99% ee) and substantial deuterium incorporation. : Catalysis; Organic Chemistry; Chemical Synthesis Subject Areas: Catalysis, Organic Chemistry, Chemical Synthesis