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

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• 作者：J. Stephen Clark ; Rapha毛lle Berger ; Stewart T. Hayes ; Hans Martin Senn ; Louis J. Farrugia ; Lynne H. Thomas ; Angus J. Morrison ; Luca Gobbi
• 刊名：The Journal of Organic Chemistry
• 出版年：2013
• 出版时间：January 18, 2013
• 年：2013
• 卷：78
• 期：2
• 页码：673-696
• 全文大小：945K
• 年卷期：v.78,no.2(January 18, 2013)
• ISSN：1520-6904

文摘

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鈥揂lder 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鈥揂lder cycloaddition reaction can be employed as advanced intermediates to prepare a wide range of cladiellin natural products.