Blue-light-promoted radical C-H azolation of cyclic nitrones enabled by Selectfluor®

An original approach to achieve the C(sp(2))-H azolation of cyclic aldonitrones mediated by Selectfluor (R) has first been employed. By exploiting a metal-free, visible-light-promoted cross-dehydrogenative C-N coupling reaction between model aldonitrones, 2H-imidazole 1-oxides, and NH-containing azoles, a series of novel azaheterocyclic derivatives have been obtained in yields up to 94%. The elaborated protocol has proved to be appropriate for gram-scale processes and displayed potential for utilization in the synthesis of novel structural analogues of lanabecestat. Besides, mechanistic studies have revealed that this coupling reaction is likely to proceed via a nitroxide-involving radical pathway, encompassing a chain of electron transfer events, such as hydrogen atom transfer (HAT) and single electron transfer (SET).

Automated summary

An innovative approach was used to achieve the C(sp(2))-H azolation of cyclic aldonitrones mediated by Selectfluor(R). Through a metal-free, visible-light-promoted cross-dehydrogenative C-N coupling reaction, a series of novel azaheterocyclic derivatives were obtained with yields up to 94%. Mechanistic studies suggest that this coupling reaction likely proceeds via a nitroxide-involving radical pathway.