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 journalArticle

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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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Biological Products
Cycloaddition
Ketones
Ether
Samarium
Rhodium
Cyclization
Iodides
Aldehydes
Copper
Esters
Metals
Catalysts
cladiellin A

Cite this

Clark, J. S., Berger, R., Hayes, S. T., Senn, H. M., Farrugia, L. J., Thomas, L., ... 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

Total Syntheses of Multiple Cladiellin Natural Products by Use of a Completely General Strategy. / Clark, J. Stephen; Berger, Raphaëlle; Hayes, Stewart T.; Senn, Hans Martin; Farrugia, Louis J.; Thomas, Lynne; Morrison, Angus J.; Gobbi, Luca.

In: Journal of Organic Chemistry, Vol. 78, No. 2, 2013, p. 673-696.

Research output: Contribution to journalArticle

Clark, JS, Berger, R, Hayes, ST, Senn, HM, Farrugia, LJ, Thomas, L, Morrison, AJ & Gobbi, L 2013, 'Total Syntheses of Multiple Cladiellin Natural Products by Use of a Completely General Strategy', Journal of Organic Chemistry, vol. 78, no. 2, pp. 673-696. https://doi.org/10.1021/jo302542h
Clark, J. Stephen ; Berger, Raphaëlle ; Hayes, Stewart T. ; Senn, Hans Martin ; Farrugia, Louis J. ; Thomas, Lynne ; Morrison, Angus J. ; Gobbi, Luca. / Total Syntheses of Multiple Cladiellin Natural Products by Use of a Completely General Strategy. In: Journal of Organic Chemistry. 2013 ; Vol. 78, No. 2. pp. 673-696.
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