Three-component synthesis of β-thio tertiary alkylamines from simple alkenes via S H 2 homolytic substitution
- Hongyu Wang
- Ting Wang
- Yang Li
- Qianyu He
- Wenxuan Ma
- Xinyu Guan
- Yifei Li
- Yongli Bao
- Yongyun Zhao
- Qian Zhang
- Neil Vasdev
- Chao Zheng
- Junkai Fu
2026-01-09
Alkene difunctionalization via electrophilic aminyl radical cations offers a straightforward route to complex tertiary alkylamines widely occurring in biologically active molecules. However, only a limited variety of third reaction components have been hitherto introduced because of the challenges in capturing transient C(sp 3 )-centered radical intermediates under acidic conditions, and structurally specific alkenes are usually required. Herein, we report a copper-catalyzed three-component aminothiolation reaction, enabling the first incorporation of S-based functionalities across simple alkenes to synthesize β-thio tertiary alkylamines. This protocol works well for both aryl and unactivated alkenes with a broad functional group compatibility and is applicable to ─SCF 3 , ─SCN, and ─SBz groups. Mechanistic investigations reveal a key bimolecular homolytic (S H 2) substitution process that efficiently traps the nascent C(sp 3 )-centered radical intermediates in acidic media and facilitates the C─S bond formation with high regioselectivity and even primary enantiocontrol. The introduced S-based functionality can improve the performance of pharmaceuticals such as Fentora.