Stereoselective Synthesis of Substituted Oxocene Cores by Lewis Acid Promoted Cyclization

Substituted oxocene derivatives have been synthesized by Lewis acid catalyzed reactions of ε-hydroxyalkene and substituted aromatic aldehydes. The Cu(OTf)2-bis-phosphine catalyzed reaction typically provides substituted dihydropyran derivatives through an olefin migration followed by a Prins cyclization. The corresponding reaction catalyzed by TMSOTf or BF3·OEt2 provided eight-membered cyclic ethers (oxocenes), selectively. This methodology provides convenient access to a variety of 2,4,8-trisubstituted oxocenes in good yields and excellent diastereoselectivities.