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，模型酯的烯醇化锂与Me_2SiCl_2发生Ireland-Claisen重排反应，立体选择性地得到所需的柠檬苦素骨架。氯二甲基甲硅烷基的配位将归因于Z-甲硅烷基烯酮缩醛的优势，产生所需的重排产物。这种立体化学的远程诱导是通过将氯二甲基硅烷螯合到相邻的内酯羰基的第一个实例。在这项研究中，我们开发了这种类型的远程控制Claisen重排反应，适用于合成clutilitane，改性的拉布拉多二萜来自埃塞俄比亚的大戟。该天然产物具有与沙特丁相似的结构，沙特丁显示出具有体内非胰岛素依赖性降血糖活性。我们计划用遥控器来合成栽培品 关于我们 Claisen重排反应重排反应的前体由烯丙醇和双环酸通过分子内Diels-Alder反应合成。烯丙基酯与LHMDS Me_2SiCl_2在甲苯中进行Claisen重排反应，以55%的产率选择性地得到了具有三个相邻立体中心的目标骨架。另一方面，我们还研究了另一种独特的Claisen重排。Claisen重排或α-溴代酯重排被称为Reformatsky-Claisen重排，但这种方法并不经常应用于天然产物的合成，即使它可以在无碱，温和的条件下进行。我们发现烯丙基环己基酯与In、InCl_3、TMSCl和Et_3N的Reformatsky-Claisen重排反应以良好的产率提供了具有四元中心的重排产物。由于后期金属如铟能够与氧原子配位，这种Reformatsky-Claisen重排也有可能应用于远程螯合控制反应。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