General Access to Tacamine and Vinca-Eburna Alkaloids through Tandem Non-Biomimetic Oxidation of Dihydropyridines/Zn-Mediated Radical Addition Processes − Unexpected Facial Selectivity of Flattened Cyclohexyl-Type Radicals

A general route to the eburnamine-vincamine and tacamine indole alkaloid groups has been developed. The key features of the synthetic strategy are the halocyclization of a dihydropyridine (a non-biomimetic oxidation of these compounds) and the radical addition of the resulting halo derivative to activated alkenes. The latter process shows an unusual stereoselectivity, favouring the generation of a cis stereochemistry in a 1,2-disubstituted 6-membered ring. Theoretical calculations suggest conformational control at the intermediate radical level, and a preferential face selectivity producing the observed products.