Protecting-group-free synthesis of Lycojapomine alkaloids enabled by radical dearomatization of a pyrrole

Alkaloids represent one of the most important and largest classes of natural products, that are defined by carrying one or more basic nitrogen atoms. These secondary metabolites have given way to numerous approved drugs and advancements in the medical sciences.1,2 Their preparation in the laboratory remains tedious however, broadly hampered by nitrogen’s nucleophilic nature and susceptibility to oxidation. To address this problem, a large number of protecting groups have been developed over the last decades to temper the reactivity of necessary nitrogen atoms and achieve the synthesis of the corresponding alkaloid.3 This often leads to an increased step-count and synthetic inefficiency, disrupting the further optimization and investigation of their biological properties.4 Here we address this problem, by achieving the synthesis of a class of complex Lycojapomine alkaloids, utilizing a photo-induced radical dearomatization of a pyrrole derivative and a subsequent ionic functionalization cascade. The chemical transformations utilized shape the way for future alkaloid syntheses and showcase the advantages of starting from simple aromatic heterocyclic starting materials, eliminating the need for any protecting groups.5,6