title: Total syntheses of multiple cladiellin natural products by use of a completely general strategy.
abstract: The enantioselective total syntheses of 10 cladiellin natural products have been completed, starting from the known allylic alcohol (+)-14, which can be prepared in large quantities. The bridged tricyclic core of the cladiellins has been constructed via three ring-forming reactions: (i) an intramolecular reductive cyclization between an aldehyde and an unsaturated ester, mediated by samarium(II) iodide, to form a tetrahydropyranol; (ii) reaction of a metal carbenoid, generated from a diazo ketone, with an ether to produce an ylide-like intermediate that rearranges to produce E- or Z-oxabicyclo[6.2.1]-5-undecen-9-one; and (iii) a Diels-Alder cycloaddition reaction to construct the third ring found in the core structure of the cladiellins. The key ring-forming reaction, in which a diazo ketone is converted into a bridged bicyclic ether, can be tuned to give either of the isomeric oxabicyclo[6.2.1]-5-undecen-9-ones as the major product by switching from a copper to a rhodium catalyst and selecting the appropriate reaction conditions. The tricyclic products obtained from the three-step sequence involving the Diels-Alder cycloaddition reaction can be employed as advanced intermediates to prepare a wide range of cladiellin natural products.
authors.affiliation: WestCHEM, School of Chemistry, Joseph Black Building, University of Glasgow, University Avenue, Glasgow G12 8QQ, United Kingdom. stephen.clark@glasgow.ac.uk
authors.forename: J Stephen
authors.initials: JS
authors.lastname: Clark
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Berger
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Hayes
authors.forename: Hans Martin
authors.initials: HM
authors.lastname: Senn
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Farrugia
authors.forename: Lynne H
authors.initials: LH
authors.lastname: Thomas
authors.forename: Angus J
authors.initials: AJ
authors.lastname: Morrison
authors.forename: Luca
authors.initials: L
authors.lastname: Gobbi
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D015394:Molecular Structure; D020005:Propanols / Q000737:chemistry*; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D001688:Biological Products; D020005:Propanols; D013256:Steroids; C506145:cladiellin A; C006463:allyl alcohol