Double Intramolecular SN‘ O-Cyclization for Stereoselective Synthesis of Bistetrahydrofuran Core of Acetogenins

A C 2 -symmetric bistetrahydrofuran core of acetogenins has been prepared via double intramolecular S N ‘ O -cyclization reactions. Approaches using readily prepared both E - and Z -olefin substrates are investigated. The cyclization of E -olefins gave a mixture of two diastereomers with low selectivity, while the corresponding Z -olefins predominantly provided a desired trans, trans -bistetrahydrofuran product. The high diastereoselectivity is presumably controlled by a hydrogen-bonding transition state. An efficient enantioselective synthesis of this C 2 -symmetric bistetrahydrofuran is also described. Sharpless asymmetric dihydroxylation was used for this approach.