Synthetic studies on biologically active natural products using palladium-promoted cyclization

The use of palladium complexes as reagents for the synthesis of biologically active natural products has been under development for at least the past three decades, and many elegant total syntheses of structurally complicated natural products, possessing pharmacologically important properties, have been realized employing Heck reaction, cycloisomerization process, and allylic alkylation reaction. In our recent contribution to this area, we would like to describe total syntheses of aphidicolin (diterpene), pumiliotoxin C (alkaloid), methyl pederate (left segment of mycalamides), hirsutene (sesquiterpene), stemodin (diterpene), and methyl atis-16-en-19-oate (diterpene) using palladium-promoted cyclization as key step. Although the palladium-promoted cycloalkenylation reaction of an olefinic silyl enol ether is a powerful strategy for construction of polycyclic system, relatively little is known about successful application of the above reaction to biologically active natural product syntheses. Herein we report the development of novel palladium-catalyzed cycloalkenylation reaction of cross-conjugated silyl enol ethers and its application to a tetracyclic diterpene synthesis.