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.

目前人们对用镧系试剂进行有机合成的反应非常感兴趣。特别是碘化钐（SmI_2）在碳-碳键形成反应中起着重要作用，各种分子内反应已成为人们关注的焦点。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。（2Z）-2-甲基-7-氧癸烯-2-烯- 1,10 -二酸衍生物在四氢呋喃中与SmI_2反应，引起级联还原环化- dieckmann缩合-内酯化反应，得到6-甲基-10-氧癸烯环[4.3.2.0^<1,5>]十一烷- 7,11 -二酮，对应于花青素- an和赤霉素的A/B环体系。二甲基(2Z)-2-甲基-8-氧基-2-烯- 1,10 -二酸酯与SmI_2反应得到7-甲基-11-氧基环[5.3.2.0^<1,6>]十一烷- 8,12 -二酮，对应于瑞松内酯的A/B环体系。用类似的方法合成了银杏内酯的部分结构：7-氧杂环[6.3.0.0^<1,5>]十一烷-6- 1体系。研究了级联环化在赤霉素合成中的应用。C/D环体系的构建包括两个关键步骤：2-环己烯衍生物与烯烯的立体选择性光环化形成8-亚甲基双环[4.2.0]辛烷-2- 1体系和smi_2诱导的pinacol偶联反应。smi_2诱导的(2Z)-2-甲基-7-oxods-2-ene1, 10-dioate衍生物的C/D环体系的级联环化产生了完全功能化的gibbane骨架，产率很高。由此建立了用单电子转移试剂SmI_2从简单无环化合物中直接得到含γ-内酯的双环体系的有效一步法。通过这些温和的条件，使用强碱性条件的迪克曼冷凝是避免和良好的立体控制新形成的环状结在产品是可能的。

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）。