N-Chloroamines as substrates for metal-free photochemical atom-transfer radical addition reactions in continuous flow

Abstract

N-Chloroamines have recently seen interest as substrates for atom-transfer radical addition (ATRA) reactions with olefins, to form β-chloroamine products, with complete atom incorporation. We report the development of a fully continuous method for N-chloroamine formation and photochemical reaction, utilizing membrane separation to purify the reactive intermediate species. Through detailed reaction optimization, supported by computational studies, we have determined that this type of reaction can be activated by direct substrate irradiation or via a range of triplet sensitizers at different wavelengths (up to 540 nm), allowing access to more favorable and sustainable reaction conditions. A number of substrates were reacted under sensitized or unsensitized conditions and the longer-term stability of the process was demonstrated in a 4.5 h experiment, achieving 94% yield and a throughput of 21.2 g h⁻¹. This study serves to bring N-chloroamines to the fore as ATRA substrates, for implementation in efficient and sustainable synthetic routes.