title: A study of exocyclic radical reductions of polysubstituted tetrahydropyrans.
abstract: Exocyclic radical reductions were thoroughly investigated in the context of the synthesis of polysubstituted tetrahydropyrans, which are found in numerous macrolides. The radical precursors studied herein were generated by tandem cycloetherification and iodoetherification reactions or, alternatively, by semicyclic acetals substitutions. DFT calculations (BHandHLYP/TZVP) performed at the transition-state level for the hydrogen radical delivery are in good accordance with the experimental data and enabled the identification of important conformational factors that govern the selectivities obtained. This study demonstrates that both the preferred reactive conformation of the radical and steric interactions with the incoming hydride have to be considered in order to fully rationalize the levels of diastereoselection generated in acyclic free-radical processes.
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM), Bio-Organic Chemistry Laboratory, 110 avenue des Pins Ouest, Montréal, Québec, Canada H2W 1R7.
authors.forename: François
authors.initials: F
authors.lastname: Godin
authors.forename: Michel
authors.initials: M
authors.lastname: Prévost
authors.forename: Frédérick
authors.initials: F
authors.lastname: Viens
authors.forename: Philippe
authors.initials: P
authors.lastname: Mochirian
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Brazeau
authors.forename: Serge I
authors.initials: SI
authors.lastname: Gorelsky
authors.forename: Yvan
authors.initials: Y
authors.lastname: Guindon
mesh_terms: D000080:Acetals / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D007476:Ionophores / Q000138:chemical synthesis*; D011422:Propionates / Q000737:chemistry; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory; D013237:Stereoisomerism; D000095662:Polyether Polyketides
chemical_list: D000080:Acetals; D005609:Free Radicals; D007476:Ionophores; D011422:Propionates; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides; C043279:zincophorin; C013612:narasin