Development of New Skeletal Transformations of Polycyclic Methylenecyclobutyl Ketones and Their Application

在本研究中，我们对相应的环烯酮与烯烯光环加成制备的多环亚甲基环丁基酮的骨架重排进行了系统的研究，以开发构建功能性和有用的多环化合物的新方法。此外，为了说明该方法的实用性，我们还对一些萜类化合物的合成进行了研究。含烷基取代基的6-4熔酮与h2so_4、p-TsOH、CF_3SO_3H、BF_3、OEt2、FeCl_3、AlCl_3、TiCl_4、BCl_3等酸反应得到了不同的产物。在甲基和乙基衍生物中，环烯酮主要由TiCl_4和BCl_3合成，环己酮主要由其他酸合成。而在异丙基和叔丁基衍生物中，与TiCl_4和BCl_3合成双环[4.2.1]壬酮的产率较高，与其他酸合成双环[4.3.0]壬酮的产率较高。对酸的反应性差异可以用酸对底物羰基的亲和力而不是对外亚甲基的亲和力来解释。此外，根据所使用的酸，产物可以分为两类，其差异可能是由于碳阳离子中间体依赖于桥头堡取代基的稳定性。利用这一重排方案作为关键步骤，实现了(*)-戊烯和(*)-四甲基地中海醇B的全合成。此外，抗癌萜类紫杉醇的合成研究也在进行中。

In this research, we have carried out the systematic investigation of skeletal rearrangements of polycyclic methylenecyclobutyl ketones prepared easily by photocycloaddition of corresponding cyclic enones to allene to develop the new method for construction of functional and useful polycyclic compounds. Furthermore, in order to exemplify the utility of the method, we have also done the synthetic study of some terpenoids. Reactions of 6-4-fused ketones bearing alkyl substituents at the C6 with acids such as H2S0_4, p-TsOH, CF_3SO_3H, BF_3 OEt2, FeCl_3, AlCl_3, TiCl_4, and BCl_3 gave various kinds of products. In the cases of the methyl and ethyl derivatives, cyclooctenones were obtained mainly using TiCl_4 and BCl_3, while cyclohexenones were major products using the other acids. In the cases of isopropyl and tert-butyl derivatives, however, bicyclo[4.2.1]nonanones were formed in good yields with TiCl_4 and BCl_3, and bicyclo[4.3.0]nonanones were produced with the other acids. The difference of the reactivity toward acids may be explained by the affinity of the acid to the carbonyl group of the substrate prefer to the exo-methylene moiety. Also, the products can be divided into two groups by acid used, and the difference may be attributed to the stability of the carbocation intermediates dependent on the bridgehead substituents. Utilizing this rearrangement protocol as a key step, total syntheses of (*)-pentalenene and (*)-tetramethylmediterraneol B have been achieved. Furthermore, the synthetic study on the anticancer terpenoid taxol is in progress.