Quinine synthesis studies: a radical-ionic annulation via Mn-mediated addition to chiral N-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.
Korapala
Chandra Sekhar
CS
Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, USA.
Qin
Jun
J
Friestad
Gregory K
GK
D000475:Alkenes / Q000737:chemistry; D002384:Catalysis; D002929:Cinchona; D006835:Hydrazones / Q000737:chemistry*; D006847:Hydrocarbons, Iodinated / Q000737:chemistry; D008345:Manganese / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011803:Quinine / Q000138:chemical synthesis* / Q000737:chemistry
D000475:Alkenes; D006835:Hydrazones; D006847:Hydrocarbons, Iodinated; D008345:Manganese; D011803:Quinine