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

C. Jacob, H. Baguia, A. Dubart, S. Oger, P. Thilmany, J. Beaudelot, C. Deldaele, S. Peruško, Y. Landrain, B. Michelet, S. Neale, E. Romero, C. Moucheron, V. Van Speybroeck, C. Theunissen, G. Evano
Nature Communications
13, 560


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.

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