title: Irreversible endo-selective diels-alder reactions of substituted alkoxyfurans: a general synthesis of endo-cantharimides.
abstract: The [4+2] cycloaddition of 3-alkoxyfurans with N-substituted maleimides provides the first general route for preparing endo-cantharimides. Unlike the corresponding reaction with 3H furans, the reaction can tolerate a broad range of 2-substitued furans including alkyl, aromatic, and heteroaromatic groups. The cycloaddition products were converted into a range of cantharimide products with promising lead-like properties for medicinal chemistry programs. Furthermore, the electron-rich furans are shown to react with a variety of alternative dienophiles to generate 7-oxabicyclo[2.2.1]heptane derivatives under mild conditions. DFT calculations have been performed to rationalize the activation effect of the 3-alkoxy group on a furan Diels-Alder reaction.
authors.affiliation: Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London, WC1H 0AJ (UK).
authors.forename: Robert W
authors.initials: RW
authors.lastname: Foster
authors.forename: Laure
authors.initials: L
authors.lastname: Benhamou
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Porter
authors.forename: Dejan-Krešimir
authors.initials: DK
authors.lastname: Bučar
authors.forename: Helen C
authors.initials: HC
authors.lastname: Hailes
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Tame
authors.forename: Tom D
authors.initials: TD
authors.lastname: Sheppard
mesh_terms: D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D061565:Cycloaddition Reaction / Q000379:methods*; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry*; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry; D008958:Models, Molecular
chemical_list: C000603893:7-oxabicyclo(2.2.1)heptane; D000438:Alcohols; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005663:Furans; D008301:Maleimides; C059688:alkoxyl radical
keywords: cantharimides; cycloadditions; dienes; furans; phthalimide