10 触媒的環化アルケニル化反応を利用する生理活性天然物の合成研究(口頭発表の部)

抄録

In 1979, Ito and Saegusa et al. discovered that the corresponding silyl enol ethers of alkenyl ketones provided the β,γ-unsaturated cyclic ketones in the presence of Pd(II). This methodology has proven to be a powerful tool for the synthesis of complex. polycyclic compounds. However, the process employing stoichiometric amounts of Pd(OAc)_2 suffers from low yields on large scale. To solve this problem, we have developed a novel palladium-catalyzed cycloalkenylation of the olefinic tert-butyldimethylsilyl enol ethers, e.g. 1→2, and the methodology was successfully adapted for the syntheses of polycyclic natural products, such as (-)-methyl atis-16-en-19-oate (3), (-)-methyl trachyloban-19-oate (4), (-)-methyl kaur-16-en-19-oate (5), and C_<20> gibberellins (6, 7, and 8) (Scheme 1). The search for the improvement of the palladium-catalyzed cycloalkenylation has been continued, with the goal of increasing the diversity of possible substrates and reaction products. We have developed a convenient, novel process to construct bicyclo[3.3.0]octane derivatives, potential synthons for the syntheses of linear and angular triquinane sesquiterpenes, such as capnellenes and silphinenes. Although the product yields are moderate, the palladium-catalyzed cycloalkenylations can be adaptable for the construction of bicyclo[4.3.0]nonane compounds (hydrindane systems). Interestingly, the palladium-catalyzed cycloalkenylation of the silyl enol ether (25) gave the tricyclic compound (26). In addition, the catalytic cycloalkenylation turned out to be adaptable to a tandem process. The tricyclic compound 28, the basic framework of cedrene (29), was prepared through the above protocol. Finally, a synthesis of aphidicolin (30) has been demonstrated using the palladium-catalyzed cycloalkenylation.