Base- and acid-catalyzed intramolecular oxy-Michael reaction for the synthesis of tetrahydrofuran ring

Base- and acid-catalyzed intramolecular oxy-Michael reactions are reported. Three ε-hydroxy α,β-unsaturated ketones 1, 2, and 3 and one ester 4 were cyclized in 5-exo-trigonal fashion to afford 2,5-disubstituted tetrahydrofurans in good yields. The substituent at the γ-hydroxy group and its stereochemistry influenced the stereoselectivity of the THF products. The precursor 2 bearing an (R)-γ-hydroxy group gave 2,5-trans-6 exclusively. In contrast, 3, bearing an (S)-γ-hydroxy group, gave only 2,5-cis-7 under acidic conditions but gave a mixture of 2,5-trans and 2,5-cis isomers of 7 under basic conditions. On the other hand, in the absence of a hydroxyl group at the γ-position, the cyclization conducted under both basic and acidic reaction conditions provided a mixture of 2,5-trans- and 2,5-cis isomers of 5 and 8.

165