Total Syntheses of Multiple Cladiellin Natural Products by Use of a Completely General Strategy

J. Stephen Clark, Raphaëlle Berger, Stewart T. Hayes, Hans Martin Senn, Louis J. Farrugia, Lynne Thomas, Angus J. Morrison, Luca Gobbi

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29 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)673-696
Number of pages24
JournalJournal of Organic Chemistry
Volume78
Issue number2
DOIs
Publication statusPublished - 2013

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    Clark, J. S., Berger, R., Hayes, S. T., Senn, H. M., Farrugia, L. J., Thomas, L., Morrison, A. J., & Gobbi, L. (2013). Total Syntheses of Multiple Cladiellin Natural Products by Use of a Completely General Strategy. Journal of Organic Chemistry, 78(2), 673-696. https://doi.org/10.1021/jo302542h