title: Intermolecular radical addition to N-acylhydrazones as a stereocontrol strategy for alkaloid synthesis: formal synthesis of quinine.
abstract: Stereocontrolled Mn-mediated radical addition of alkyl iodides to chiral N-acylhydrazones enables strategic C-C bond disconnection of chiral amines. This strategy was examined in the context of a total synthesis of quinine, generating new findings of functional group compatibility leading to a revised strategy. Completion of a formal synthesis of quinine is presented, validating the application of Mn-mediated radical addition as a useful new C-C bond construction method for alkaloid synthesis. The Mn-mediated addition generates the chiral amine substructure of quinine with complete stereocontrol. Subsequent elaboration includes two successive ring closures to forge the azabicyclo[2.2.2]octane ring system of quincorine, linked to quinine through two known reactions.
authors.affiliation: Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, USA. gregory-friestad@uiowa.edu
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Friestad
authors.forename: An
authors.initials: A
authors.lastname: Ji
authors.forename: Chandra Sekhar
authors.initials: CS
authors.lastname: Korapala
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
mesh_terms: D005609:Free Radicals / Q000737:chemistry; D006835:Hydrazones / Q000737:chemistry*; D008968:Molecular Conformation; D011803:Quinine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D005609:Free Radicals; D006835:Hydrazones; D011803:Quinine