Quinine Synthesis Studies: A Radical−Ionic Annulation via Mn-Mediated Addition to Chiral <i>N</i>-Acylhydrazones

A radical−ionic annulation approach to functionalized perhydroisoquinolines involving Mn-mediated coupling of alkyl iodides and chiral N-acylhydrazones was achieved using only 1.25 equiv of the alkyl iodide. Application of this reaction to alkene-containing substrates en route to quinine offered modest yields, decreasing on scaleup. Control experiments revealed that the alkene interfered with the coupling reaction. A revised approach involving prior oxidation of the alkene offered 93% yield in the Mn-mediated coupling, with the adduct obtained as a single diastereomer.