Studies for the Synthesis of Xenicane Diterpenes. A Stereocontrolled Total Synthesis of 4-Hydroxydictyolactone

摘要

The stereocontrolled total synthesis of 4-hydroxydictyolactone (>4), a member of the xenicane diterpene family of natural products, is described. These studies feature the development of the B-alkyl Suzuki cross-coupling reaction for direct access to (E)-cyclononenes from acyclic precursors. The Ireland-Claisen rearrangement is effectively utilized to establish the backbone asymmetry of the contiguous C2, C3, C10 stereotriad of >4. The synthesis strategy has devised an intramolecular Nozaki-Hiyama reductive allylation of a formate ester for the stereoselective formation of five-membered lactols >22. In addition, an internally directed SE' propargylation using allenylmagnesium bromide is described to establish the stereochemistry of the C4 alcohol in >27, and the terminal alkyne is subsequently functionalized via a regioselective syn-silylstannylation to yield >30. Finally, the stereocontrolled phenylselenylation of the ester enolate derived from >43 leads to the desired syn-oxidative elimination to yield the natural product >4.