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

Abstract

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.

Aromatic Cations from Oxidative Carbon–Hydrogen Bond Cleavage in Bimolecular Carbon–Carbon Bond Forming Reactions

“…Overman has reported a similar reactivity pattern for intramolecular vinylsilane additions into oxocarbenium ions. 15 …”

Iron-Catalyzed Prins–Peterson Reaction for the Direct Synthesis of Δ4-2,7-Disubstituted Oxepenes

“…Overman and co-workers obtained unsaturated oxacycles from mixed acetals, and later Yu and co-workers developed a two-step synthesis of oxepenes using palladium catalysis. However, an undesired excess of a harsh Lewis acid and highly toxic organotin reagents were used, giving rise to undesired byproducts (Scheme ). …”

Unexpected Domino Silyl-Prins/Aryl Migration Process from Geminal Vinylsilyl Alcohols

“…Final desilylation by in situ generated HF acid would explain the formation of the final product ( Scheme 1 c). 6 …”

“…Prins cyclization would provide a carbocation α to silicon, which then could eliminate an adjacent proton to give a silylated dihydropyran. Final desilylation by in situ generated HF acid would explain the formation of the final product (Scheme c) …”