title: Synthesis of 2,6-trans- and 3,3,6-trisubstituted tetrahydropyran-4-ones from Maitland-Japp derived 2H-dihydropyran-4-ones: a total synthesis of diospongin B.
abstract: 6-Substituted-2H-dihydropyran-4-one products of the Maitland-Japp reaction have been converted into tetrahydropyrans containing uncommon substitution patterns. Treatment of 6-substituted-2H-dihydropyran-4-ones with carbon nucleophiles led to the formation of tetrahydropyran rings with the 2,6-trans-stereochemical arrangement. Reaction of the same 6-substituted-2H-dihydropyran-4-ones with l-Selectride led to the formation of 3,6-disubstituted tetrahydropyran rings, while trapping of the intermediate enolate with carbon electrophiles in turn led to the formation 3,3,6-trisubstituted tetrahydropyran rings. The relative stereochemical configuration of the new substituents was controlled by the stereoelectronic preference for pseudo-axial addition of the nucleophile and trapping of the enolate from the opposite face. Application of these methods led to a synthesis of the potent anti-osteoporotic diarylheptanoid natural product diospongin B.
authors.affiliation: Department of Chemistry, University of York, Heslington, York, North Yorks YO10 5DD, UK. paul.clarke@york.ac.uk.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Clarke
authors.affiliation: Department of Chemistry, University of York, Heslington, York, North Yorks YO10 5DD, UK. paul.clarke@york.ac.uk.
authors.forename: Nadiah Mad
authors.initials: NM
authors.lastname: Nasir
authors.affiliation: Department of Chemistry, University of York, Heslington, York, North Yorks YO10 5DD, UK. paul.clarke@york.ac.uk.
authors.forename: Philip B
authors.initials: PB
authors.lastname: Sellars
authors.affiliation: Department of Chemistry, University of York, Heslington, York, North Yorks YO10 5DD, UK. paul.clarke@york.ac.uk.
authors.forename: Alejandra M
authors.initials: AM
authors.lastname: Peter
authors.affiliation: Department of Chemistry, University of York, Heslington, York, North Yorks YO10 5DD, UK. paul.clarke@york.ac.uk.
authors.forename: Connor A
authors.initials: CA
authors.lastname: Lawson
authors.affiliation: Department of Chemistry, University of York, Heslington, York, North Yorks YO10 5DD, UK. paul.clarke@york.ac.uk.
authors.forename: James L
authors.initials: JL
authors.lastname: Burroughs
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D001880:Boranes / Q000138:chemical synthesis / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D001880:Boranes; D011714:Pyrans; C521318:diospongin B; C533353:selectride