Three-component synthesis of β-thio tertiary alkylamines from simple alkenes via S _H 2 homolytic substitution

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(sp³)-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 ─SCF₃, ─SCN, and ─SBz groups. Mechanistic investigations reveal a key bimolecular homolytic (S_H2) substitution process that efficiently traps the nascent C(sp³)-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.