Total Synthesis of (+)-Isolaurepinnacin. Use of Acetal-Alkene Cyclizations To Prepare Highly Functionalized Seven-Membered Cyclic Ethers

The first synthesis of the title compound is described. The synthesis features an acetal-vinylsilane cyclization to stereoselectively form the cis -2,7-disubstituted oxepene ring and introduce Δ 4 unsaturation. Starting with (2 R,3 S )-2,3-epoxypentan-1-ol ( 16 ), mixed acetal 10 is formed in five steps and 72% overall yield. Treatment of 10 with excess BCl 3 in CH 2 Cl 2 at −78 → 0 °C promotes cyclization to afford Δ 4 -oxepene 39 in 90% yield after deprotection of the silyl ether. Elaboration of the ( E )-enyne functionality of the six-carbon side chain completes the synthesis of (+)-isolaurepinnacin.