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Intermolecular radical addition to N-acylhydrazones as a stereocontrol strategy for alkaloid synthesis: formal synthesis of quinine
Journal article   Peer reviewed

Intermolecular radical addition to N-acylhydrazones as a stereocontrol strategy for alkaloid synthesis: formal synthesis of quinine

Gregory K Friestad, An Ji, Chandra Sekhar Korapala and Jun Qin
Organic & biomolecular chemistry, Vol.9(11), pp.4039-4043
06/07/2011
DOI: 10.1039/c1ob05219e
PMCID: PMC4114234
PMID: 21537510
url
http://doi.org/10.1039/c1ob05219eView
Open Access

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.
Quinine - analogs & derivatives Free Radicals - chemistry Stereoisomerism Molecular Conformation Quinine - chemical synthesis Hydrazones - chemistry Quinine - chemistry

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