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

• Published in: Journal of the American Chemical Society Vol. 119; no. 10; pp. 2446 - 2452
• Main Authors: Berger, Daniel, Overman, Larry E, Renhowe, Paul A
• Format: Journal Article
• Language: English
• Published: American Chemical Society 12.03.1997
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja964080b

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 Δ4 unsaturation. Starting with (2R,3S)-2,3-epoxypentan-1-ol (16), mixed acetal 10 is formed in five steps and 72% overall yield. Treatment of 10 with excess BCl3 in CH2Cl2 at −78 → 0 °C promotes cyclization to afford Δ4-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.