Tetrahydropyran rings from a Mukaiyama-Michael cascade or rearrangement of dihydropyrans

WCC 3

Autumn Maruniak, Megan L. Bolla, and Scott D. Rychnovsky. Department of Chemistry, University of California-Irvine, 516 Rowland Hall, Irvine, CA 92697-2025
We have investigated annulation reactions leading to tetrahydropyrans. Homoallylic enol ethers react with α,β-unsaturated ketones by a Mukaiyama-Michael addition in the presence of titanium tetrabromide to form an intermediate oxocarbenium ion, which then undergoes a 2-oxonia-Cope rearrangement. The zwitterion then collapses to form a tetrahydropyran, but when the allyl group of the initial enol ether is replaced by a crotyl group, sigmatropic rearrangement does not occur and only a diastereomeric mixture of the bromine-trapped tetrahydropyran forms. We have also investigated the formation of tetrahydropyrans from the rearrangement of dihydropyrans. The dihydropyran forms a mixture of endo products from a hetero Diels-Alder reaction of an á-keto ester with a homoallylic alcohol. In the presence of scandium (III) triflate the dihydropyran opens to form an oxocarbenium ion, which then undergoes a sigmatropic rearrangement. The resulting zwitterion collapses to form a diastereomeric mix of tetrahydropyrans. The development of these annulation reactions will be useful new tools for the synthesis of complex natural products.