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

在本研究中，我们系统地研究了多环亚甲基环丁基酮的骨架重排反应，通过相应的环烯酮与丙二烯的光环加成反应，为构建具有功能和实用价值的多环化合物提供了新的方法。此外，为了说明该方法的实用性，我们还对一些萜类化合物进行了合成研究。含烷基团的6-4-稠酮在C6上与H_2SO_4、p-TsOH、CF_3SO_3、BF_3OEt2、FeCl3、AlCl3、TiCl4、BCl3等酸反应，得到各种产物。在甲基和乙基衍生物中，环辛烯酮主要由TiCl4和BCl3生成，而环己烯酮是使用其他酸生成的主要产物。在异丙基和叔丁基衍生物的情况下，TiCl4和BCl3以较高的产率生成双环[4.2.1]壬酮，其他酸生成双环[4.3.0]壬酮。对酸的反应活性的差异可能是由于酸对底物上的羰基的亲和力高于对亚甲基的亲和力。此外，根据所使用的酸可以将产物分为两类，这种差异可能归因于碳正离子中间体的稳定性依赖于桥头取代基。以此重排反应为关键步骤，实现了(*)-戊二烯和(*)-四甲基麦迪醇B的全合成。此外，抗癌萜类紫杉醇的合成研究正在进行中。

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.