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碳-碳骨架的立体化学。最近我们发现，模拟酯的锂烯醇酯与Me_2SiCl_2在甲苯中进行了Ireland-Claisen重排，得到了所期望的立体选择性类柠檬骨架。氯二甲基硅基的配位可归因于z -硅基烯缩醛的优势，从而产生所需的重排产物。这种远程诱导立体化学是氯二甲基硅烷与相邻内酯羰基螯合的第一个例子。在本研究中，我们开发了这种远程控制Claisen重排反应，用于合成从埃塞俄比亚大戟属植物中提取的改性的唇丹二萜。这种天然产物具有与糖苷相似的结构，具有体内非胰岛素依赖型降糖活性。我们计划利用遥控克雷森重排法合成栽培素。重排前体由烯丙醇和双环酸酯化制备，并通过分子内Diels-Alder反应易于合成。用LHMDS Me_2SiCl_2对烯丙基酯进行Claisen重排，在甲苯中有很好的选择性，以55%的收率得到了具有三个连续立体中心的所需骨架。另一方面，我们也研究了另一种独特的Claisen重排。Claisen重排或α-溴酯被称为Reformatsky-Claisen重排，然而这种方法并不常用于天然产物的合成，尽管它可以在无碱、温和的条件下进行。用In、InCl_3、TMSCl和Et_3N对烯丙基环己基酯进行Reformatsky-Claisen重排，重排产物有一个季中心，收率较高。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