Photoredox-Mediated Mono- and Difluorination of Remote Unactivated Methylene C(sp3)-H Bonds of N-Alkyl Sulfonamides

A photoredox-mediated delta-C(sp(3))-H fluorination of sulfonyl-protected primary alkylamines with Selectfluor is developed. The reaction can proceed in excellent monofluorination selectivity for amine substrates without a substituent. For alpha-substituted substrates, a slightly modified reaction conditions with two rounds of operation gives the delta,delta-difluorination products in good yield. Mechanistic studies suggest SET oxidation of sulfonamide group directly generates the key sulfonamide N radical intermediate, which triggers a 1,5-HAT process to form the delta alkyl radical.

Automated summary

A new method has been developed for the photoredox-mediated delta-C(sp(3))-H fluorination of sulfonyl-protected primary alkylamines with Selectfluor. This reaction shows excellent monofluorination selectivity for amine substrates without substituents, and slightly modified reaction conditions allow for the synthesis of delta,delta-difluorination products in good yield for alpha-substituted substrates. Mechanistic studies indicate that SET oxidation of the sulfonamide group generates the key sulfonamide N radical intermediate, triggering a 1,5-HAT process to form the delta alkyl radical.