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

Research output: Contribution to journalArticlepeer-review

33 Citations (SciVal)


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
Issue number2
Publication statusPublished - 2013


Dive into the research topics of 'Total Syntheses of Multiple Cladiellin Natural Products by Use of a Completely General Strategy'. Together they form a unique fingerprint.

Cite this