A general synthesis of azetidines by copper-catalysed photoinduced anti-Baldwin radical cyclization of ynamides

A general anti-Baldwin radical 4-exo-dig cyclization from nitrogen-substituted alkynes is reported. Upon reaction with a heteroleptic copper complex in the presence of an amine and under visible light irradiation, a range of ynamides were shown to smoothly cyclize to the corresponding azetidines, useful building blocks in natural product synthesis and medicinal chemistry, with full control of the regioselectivity of the cyclization resulting from a unique and underrated radical 4-exo-dig pathway. The construction of four-membered rings via a 4-exo-dig cyclization was originally theorized to be unfavourable and only recently shown in sparse examples. Here the authors present a photochemical, radical 4-exo-dig cyclization of ynamides to form azetidines, promoted by copper photoredox catalysis.