Total syntheses of multiple cladiellin natural products by use of a completely general strategy.
Total syntheses of multiple cladiellin natural products by use of a completely general strategy.
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DOI：
10.1021/jo302542h
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发表时间：
2013-01
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影响因子：
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通讯作者：
J. Clark;Raphaëlle Berger;Stewart T. Hayes;H. Senn;L. Farrugia;L. Thomas;Angus J. Morrison;L. Gobbi
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文献类型：
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作者：
J. Clark;Raphaëlle Berger;Stewart T. Hayes;H. Senn;L. Farrugia;L. Thomas;Angus J. Morrison;L. Gobbi
以已知的可大批量制备的烯丙醇(+)-14为起始原料，完成了10个cladiellin天然产物的对映选择性全合成。 cladiellins 的桥联三环核心是通过三个成环反应构建的：（i）醛和不饱和酯之间的分子内还原环化，由碘化钐（II）介导，形成四氢吡喃醇； (ii)由重氮酮生成的金属类胡萝卜素与醚反应生成类叶立德中间体，该中间体重排生成E-或Z-氧杂双环[6.2.1]-5-十一碳烯-9-酮； (iii) Diels-Alder环加成反应以构建在cladiellins核心结构中发现的第三个环。关键的成环反应（其中重氮酮转化为桥联双环醚）可以通过从铜催化剂切换到铑催化剂并选择适当的反应条件来调整，以得到异构的氧杂双环[6.2.1]-5-十一碳烯-9-酮作为主要产物。从涉及第尔斯-阿尔德环加成反应的三步序列获得的三环产物可用作高级中间体来制备各种克拉迪林天然产物。
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.