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

目前，在有机合成中使用稀土试剂的反应引起了人们的极大兴趣。尤其是SmI_2在碳-碳键的形成反应中是有效的，各种分子内过程引起了人们的极大关注。在本研究中，我们开发了一种有效的SMI_2诱导的级联环合反应来形成多环化合物。(2Z)-2-甲基-7-氧代-2-烯-1，10-二酸衍生物在四氢呋喃中与SnI_2反应，发生级联还原环化-Dieckmann缩合-内酯化反应，得到对应于A/B环系的6-methyl-10-oxatricyclo[4.3.2.0^&lt；1，5&gt；]undecane-7，11-二酮。(2Z)-2-甲基-8-氧杂环二酸二甲酯-2-烯-1，10-二酸二甲酯与SnI_2反应，得到了对应于7-methyl-11-oxatricyclo[5.3.2.0^&lt；1，6&gt；]undecane-8，的A/B环系的12-二酮。用类似的方法合成了银杏内酯的部分结构7-oxatricyclo[6.3.0.0^&lt；1，5&gt；]undecan-6-one体系。研究了串级环化反应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-环己烯衍生物与烯的立体选择性光环化反应，生成8-亚甲基双环[4.2.0]Octan-2-one体系和SMI_2诱导的片呐醇偶联反应。含C/D环的(2Z)-2-甲基-7-氧代-2-烯-1，10-二酸酯类化合物在SMI2作用下的级联环化反应，高产率地生成了功能齐全的吉卜兰骨架.因此，作者建立了一种用一个电子转移试剂SMI2从简单的非环化合物中直接合成γ-内酯双环体系的有效而直接的一步工艺.由于这些温和的条件，避免了使用强碱性条件进行Dieckmann缩合反应，并可以很好地控制产品中新形成的环连接.

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.