Development of useful lanthanide salt-induced cascade reactions and applications to natural products synthesis

有用的镧系盐诱导级联反应的开发及其在天然产物合成中的应用

• 批准号: 13672240
• 负责人: NAGAOKA Hiroto
• 金额: $ 2.3万
• 依托单位: MEIJI PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672240/
• 关键词: Samarium(II) iodide; cyclization; reductive coupling; gibberellins; 10-oxatricyclo[4.3.2.0^<1,5>] undecane-7, 11-diones; 11-oxatricyclo[5.3.2.0^<1,6>]undecane-8, 12-diones; spiro[4, 4]nonane; 10-oxatricyclo[4.3.2.0^<1.5>]undecane

Much interest is presently being directed to reaction using lanthanide reagent in organic synthesis. Especially, samarium(II) iodide (SmI_2) has been effective in carbon-carbon bond forming reactions and considerable attention has been focused on various intramolecular processes. In the present investigation, we developed an effective SmI_2-induced cascade cyclization to form polycyclic compounds. Treatment of (2Z)-2-methyl-7-oxodec-2-ene-1, 10-dioic acid derivatives with SmI_2 in tetrahydrofuran caused cascade reductive cyclization-Dieckmann condensation-lactonization to give 6-methyl-10-oxatricyclo[4.3.2.0^<1,5>]undecane-7, 11-diones corresponding to A/B ring system of antheridiogen-An and gibberellins. And reaction of dimethyl (2Z)-2-methyl-8-oxoundec-2-ene-1, 10-dioate with SmI_2 gave 7-methyl-11-oxatricyclo[5.3.2.0^<1,6>]undecane-8, 12-diones corresponding to A/B ring system of resenolactone. A partial structure of ginkgolides, 7-oxatricyclo[6.3.0.0^<1,5>]undecan-6-one system, was also synthesized by similar method. An application of the cascade cyclization for the synthesis of gibberellins was then investigated. The construction of the C/D ring system involves two crucial steps : stereoselective photo cyclization of 2-cyclohexene derivative with allene to form 8-methylenebicyclo[4.2.0]octan-2-one system and SmI_2-induced pinacol coupling reaction. The SmI_2-induced cascade cyclization of the (2Z)-2-methyl-7-oxods-2-ene1, 10-dioate derivative bearing C/D ring system produced fully functionalized gibbane skeleton in good yield.Thus the authors established an effective and direct one-step process for obtaining bicyclic ring systems with γ-lactone from simple acyclic compounds using one electron transfer reagent SmI_2. By these mild conditions, the use of strongly basic conditions for the Dieckmann condensation is avoided and good to excellent stereocontrol over newly formed ring junctures in the product is possible.

目前，人们对有机合成中使用镧系试剂的反应感兴趣。特别是碘化钐(SmI_2)在碳-碳键形成反应中非常有效，并且引起了人们对各种分子内过程的广泛关注。在本研究中，我们开发了一种有效的 SmI_2 诱导级联环化形成多环化合物。在四氢呋喃中用SmI_2处理(2Z)-2-甲基-7-氧代-2-烯-1, 10-二酸衍生物，引起级联还原环化-迪克曼缩合-内酯化，得到6-甲基-10-氧杂三环[4.3.2.0^<1,5>]十一烷-7, 11-二酮，对应于A/B环系 antheridiogen-An 和赤霉素。 (2Z)-2-甲基-8-氧代十一烷-2-烯-1, 10-二酸二甲酯与SmI_2反应得到7-甲基-11-氧杂三环[5.3.2.0^<1,6>]十一烷-8, 12-二酮，对应于雷斯烯内酯的A/B环系。采用类似方法还合成了银杏内酯的部分结构7-氧三环[6.3.0.0^<1,5>]十一烷-6-酮体系。然后研究了级联环化在赤霉素合成中的应用。 C/D环体系的构建涉及两个关键步骤：2-环己烯衍生物与丙二烯的立体选择性光环化形成8-亚甲基双环[4.2.0]辛烷-2-酮体系和SmI_2诱导的频哪醇偶联反应。 SmI_2 诱导的 (2Z)-2-methyl-7-oxods-2-ene1, 10-dioate 衍生物的 C/D 环系统级联环化以良好的收率产生了全功能化的 gibbane 骨架。因此，作者建立了一种有效且直接的一步方法，使用一种电子转移试剂 SmI_2 从简单的无环化合物中获得带有 γ-内酯的双环系统。通过这些温和的条件，避免了迪克曼缩合使用强碱性条件，并且可以对产物中新形成的环接点进行良好至极好的立体控制。

项目成果

Takehiko Yoshimitsu: "Hydroxyalkylation of α-C-H Bonds of Tetrahydrofuran with Aldehydes in the Presence of Triethylborane and tert-Buty Hydroperoxide"The Journal of Organic Chemistry. 68・2. 625-627 (2002)

Takehiko Yoshimitsu：“三乙基硼烷和叔丁基氢过氧化物存在下四氢呋喃的 α-C-H 键的羟烷基化”有机化学杂志 68・2（2002 年）。

Hiroaki Miyaoka, Toshiyuki Yokokura, Takashi Okamura, Hiroto Nagaoka and Yasuji Yamada: "Synthesis of the Optically Active Bicyclo[4.2.1]nonane Segment of Mediterraneols"Synlett. 227-230 (2002)

Hiroaki Miyaoka、Toshiyuki Yokokura、Takashi Okamura、Hiroto Nagaoka 和 Yasuji Yamada：“地中海醇光学活性双环[4.2.1]壬烷片段的合成”Synlett。

Hiroaki Miyaoka: "Synthesis of the Optically Active Bicyclo[4.2.1]nonane Segment of Mediterraneols"Synlett. 2. 227-230 (2002)

Hiroaki Miyaoka：“地中海醇的光学活性双环[4.2.1]壬烷片段的合成”Synlett。

Takehiko Yoshimitsu, Arano Y and Hiroto Nagaoka: "Hydroxyalkylation of a-C-H Bonds of Tetrahydrofuran with Aldehydes in the Presence of Triethylborane and tert-Butyl Hydroperoxide"J. Org. Chem.. 68. 625-627 (2003)

Takehiko Yoshimitsu、Arano Y 和 Hiroto Nagaoka：“在三乙基硼烷和叔丁基过氧化氢存在下，四氢呋喃的 a-C-H 键与醛的羟烷基化”J。

Takehiko Yoshimitsu: "Hydroxyalkylation of α-C-H Bonds of Tetrahydrofuran with Aldehydes in the Presence of Triethylborane and tert-Butyl Hydroperoxide"The Journal of Organic Chemistry. 68・2. 625-627 (2002)

Takehiko Yoshimitsu：“三乙基硼烷和叔丁基氢过氧化物存在下四氢呋喃的 α-C-H 键的羟烷基化”有机化学杂志 68・2（2002 年）。