POLYMER-SUPPORTED SYNTHESIS OF CYCLIC ETHERS - ELECTROPHILIC CYCLIZATION OF TETRAHYDROFUROISOXAZOLINES

The polymer-supported synthesis of cyclic ethers has been achieved usi ng an intramolecular 1,3-dipolar cycloaddition/electrophilic cyclizati on sequence. The five-step reaction scheme converts heptadienols to cy clic ethers in 21-49% overall yield from polymer-supported nitroolefin . The heptadienols were varied with a Ph, CH3, and H group in the ally lic position to give the accordingly substituted cyclic ethers. The 1, 3-dipolar cycloaddition sets three stereocenters in the tetrahydrofuro isoxazoline, and the electrophilic cyclization establishes a fourth st ereocenter in the cyclic ether. The degree of functionalization at the nitroolefin stage was determined by reduction to the primary amine an d quantification with ninhydrin. The cis cyclic ether is the predomina nt stereoisomer from the electrophilic cyclization process. This latte r step is specific for removal of only the desired cyclic ether from t he polymer support.