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

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 intramole...

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Bibliographic Details
Published in:Journal of organic chemistry 2013-01, Vol.78 (2), p.673-696
Main Authors: Clark, J. Stephen, Berger, Raphaëlle, Hayes, Stewart T, Senn, Hans Martin, Farrugia, Louis J, Thomas, Lynne H, Morrison, Angus J, Gobbi, Luca
Format: Article
Language:English
Subjects:
Biological Products - chemical synthesis
Biological Products - chemistry
Catalysis
Cyclization
Molecular Structure
Propanols - chemistry
Stereoisomerism
Steroids - chemical synthesis
Steroids - chemistry
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Summary: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.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo302542h