Prins Cyclization of Vinyl Bis-sulfides Gives Stereoselective Access to Di/Tetrahydropyrans and Pyran-4-ones

TMSOTf-mediated intramolecular Prins cyclization of vinyl bis-sulfide-tethered vinylogous carbonates gives a highly regio- and diastereoselective access to dihydropyrans. Stereoselective synthesis of tetrahydropyran-4-ones could be accomplished by a Cu(OTf) 2 -catalyzed bimolecular Prins cyclization of vinyl bis-sulfide-tethered alcohols with aldehydes/ketones. The vinyl bis-sulfide moiety provides a unified platform to three distinct oxidation states of substituted pyrans. The methodology is applied to the synthesis of (±)-centrolobine, (±)-civet, enantiomerically enriched C 2 -symmetric bis-dihydropyran and a bridged bicyclic ether featuring a trans -2,6-disubstitued THP.