Synthetic Studies of Natural Products Using By a Chelation Controlled Claisen Rearrangement

天然产物的合成往往需要各种方法来控制复杂的碳-碳骨架的立体化学。最近我们发现，在甲苯中，模型酯与Me_2SiCl2发生的Li-enolate的爱尔兰-Claisen重排反应得到了所需的柠檬酸骨架。氯代二甲基硅基的配位作用归因于Z-硅基酮缩醛的优势，从而产生所需的重排产物。这种立体化学的远程诱导是第一个通过将氯二甲基硅烷螯合到相邻的内酯羰基上的例子。在这项研究中，我们开发了这种类型的遥控Claisen重排反应，用于合成埃塞俄比亚大戟属植物中的簇内酯，修饰的拉巴丹二萜。该天然产物具有与苏豆素相似的结构，表明其在体内具有非胰岛素依赖的降血糖活性。我们计划通过远程…合成葛根素内酯更受控制的克莱森重排。通过烯丙醇和双环酸的酯化反应制备了重排前驱体，分子内Diels-Alder反应易于合成。烯丙基酯与LHMDS Me_2SiCl2在甲苯中的Claisen重排反应具有很好的选择性，得到了具有三个相邻立体中心的骨架，产率为55%。另一方面，我们还研究了另一种独特的Claisen重排。克莱森重排或α-溴酸酯被称为雷格茨基-克莱森重排，然而，将这种方法应用于天然产物的合成并不常见，即使它可以在无碱、温和的条件下进行。结果表明，烯丙基环己酯与In、InCl3、TMSCl和Et3N的Reformsky-Claisen重排反应以较高的产率提供了具有四元中心的重排产物。由于铟等晚期金属能够与氧原子配位，这种Reformsky-Claisen重排反应也有可能应用于远程络合控制反应。较少

Synthesis of natural products often requires various methods for control of stereochemistry of complicated carbon-carbon framework. Recently we found that the Ireland-Claisen rearrangement of Li-enolate of the modeled ester with Me_2SiCl_2 in toluene afforded the desired limonoid framework stereoselectively. The coordination of the chlorodimethylsilyl group would be attributed to the predominance of the Z-silyl ketene acetal, generating the desired rearranged product. This remote induction of stereochemistry was the first example by chelation of the chlorodimethylsilane to adjacent lactone carbonyl group. In this study, we developed this type of remote controlled Claisen rearrangement reactions to apply to synthesis of clutiolide, modified labdane diterpene derived from Euphorbia speicies in Ethiopia. This natural product has similar structure to saudin, which shows to possess in vivo noninsulin dependent hypoglycemic activity. We planned to synthesize of cultiolide using by the remote … More controlled Claisen rearrangement. The precursor of rearrangement was prepared by esterification of allyl alcohol and bicyclic acid, which was readily synthesize by intramolecular Diels-Alder reaction. The Claisen rearrangement of allylic ester with LHMDS Me_2SiCl_2 in toluene proceeded in a excellent selectivity to afford the desired skeleton with three contiguous stereogenic centers in 55% yield. On the other hand, we also investigated another unique Claisen rearrangement. The Claisen rearrangement or α-bromo ester has been known as Reformatsky-Claisen rearrangement, however it is not so often to apply this methodology to natural products synthesis, even though it can be performed under base-free, mild condition. We found that the Reformatsky-Claisen rearrangement of allylic cyclohexyl ester with In, InCl_3, TMSCl, and Et_3N provided the rearranged product with a quarternary center in a good yield. Since the late-period metal such as indium is capable to coordinate to oxygen atom, this Reformatsky-Claisen rearrangement has also possibility to be applied to remote chelation controlled reaction. Less