New Methodologies for Construction of Medium- and Large-sized Carbocycles

构建中型和大型碳环的新方法

• 批准号: 08454198
• 负责人: KUWAJIMA Isao
• 金额: $ 4.54万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08454198/
• 关键词: [3+2] Cycloaddition; Coriolin; Pentalenolactone G; Medium, Large-sized Carbocycles; Cyclization; Ingenol; 立体特異的[3+2]環化付加反応; 中及び大員環炭素骨格構築法; オキサシラシクロアルカン; ポリオールの立体選択的合成; [3+2]環化付加反応; 5員環炭素骨格構築法; コリオリンの不斉合成; 環状アセチレン; 環状アレン型化合物

The following synthetically useful methodologies have been developed by this research project.(1) The substrates such as 3- (alkylthio) -2- (siloxy) - and 3- (alkylthio) -2- (silylmethyl) allyl acetates have been shown as useful three carbon units for [3 + 2] cylopentanone and methylene cyclopentane annulation in the reactions with electron-rich olefins. It has also been proposed the high observed regioselectivity is due to thermodynamic control of this reaction, and excellent stereoselectivity observed in the reaction with vinylsulfides may be due to remarkable effect of sulfur having a largest HOMO coefficient. Based on this methodology, enantioselective total synthesis of coriolin has also been achieved.(2) Based on the remarkable feature of 3- (alkylthio) allylic acetates, construction of medium or large carbocycles has been examined by using substrates having appropriate olefinic moieties. Under the influence of appropriate Lewis acid, the reaction took place cleanly to afford the corresponding larger-sized carbocycles with almost complete regioselectivity.(3) For construction of a unique carbocycle of ingenol, a one step process involving cyclization followed by carbon skeleton rearrangement has been designed and examine. By using an appropriate Al reagent, the expected reaction proceeded nicely to give the product containing ingenane ABC-tricarbocycles. By utilizing the present methodology, synthetic studies on ingenol is in progress.

该研究项目开发了以下综合有用的方法。(1)底物3-（烷基硫基）-2-（硅氧基）-和3-（烷基硫基）-2-（硅甲基）烯丙基乙酸酯在与富电子烯烃的反应中作为[3 + 2]环戊酮和亚甲基环戊烷环化的有用三碳单元。还提出了高区域选择性是由于该反应的热力学控制，而与乙烯基硫化物反应中观察到的良好立体选择性可能是由于具有最大HOMO系数的硫的显著影响。在此基础上，还实现了科里林的对映选择性全合成。(2)基于3-（烷基硫代）烯丙基乙酸酯的显著特性，研究了采用合适的烯烃基的底物构建中碳环或大碳环的方法。在适当的Lewis酸的影响下，反应进行得很干净，产生了相应的大尺寸碳环，并且几乎具有完全的区域选择性。(3)为了构建独特的ingenol碳循环，设计并研究了环化-碳骨架重排的一步工艺。通过使用合适的Al试剂，预期的反应顺利进行，得到了含有ingenane abc -三碳环的产物。利用目前的方法，人们正在进行ingenol的合成研究。

项目成果

I.Kuwajima: "Control of Stereochemistry by sigma-Participation of a Silyl Group. Novel Ring Expansion Reactions of a 1-Oxa-2-Silacyclopentane Derivative" J.Org.Chem.62, No.13. 4206-4207 (1997)

I.Kuwajima：“通过甲硅烷基的 σ 参与控制立体化学。1-Oxa-2-Silacyclopentane 衍生物的新型扩环反应”J.Org.Chem.62，No.13。

I.Kuwajima: "Total Synthesis of (±)-Taxusin" J.Am.Chem.Soc.118・NO.38. 9186-9187 (1996)

I.桑岛：“(±)-紫杉素的全合成”J.Am.Chem.Soc.118·NO.38(1996)。

I.Kuwajima: "Control of Stereochemistry by σ-Participation of a Silyl Group. Novel Ring Expansion Reactions of a 1-Oxa-2-Silacyclopentane derivative" J. Org. Chem.62・No.13. 4206-4207 (1997)

I.桑岛：“通过甲硅烷基的σ-参与控制立体化学。1-Oxa-2-硅杂环戊烷衍生物的新型扩环反应”J. Org.62·No.13（1997）。

I.Kuwajima: "Highly Efficient Method for Coriolin Synthesis" Tetrahedon Lett.38, No.3. 465-468 (1997)

I.Kuwajima：“科里林合成的高效方法”Tetrahedon Lett.38，No.3。

I.Kuwajima: "Highly Efficient Method for Coriolin Synthesis" Tetrahedron Lett.38, No.3. 465-468 (1997)

I.Kuwajima：“科里林合成的高效方法”Tetrahedron Lett.38，No.3。