Synthesis of Chiral 10, 11 and 12-Membered Nitrogen and Oxygen Heterocycles by Intramolecular Nitrile Oxide Cycloaddition of Tethered N- and O-Allyl Carbohydrate Derivatives

Chiral 10 to 12-membered nitrogen and oxygen heterocycles fused to isoxazoline rings have been prepared in a highly regioselective and stereoselective manner by intramolecular nitrile oxide cycloaddition of tethered N- and O-allyl carbohydrate derivatives. The use of a –Y–Ar-CH2 tether containing a 1,2-disubstituted aromatic ring between the heteroatom attached to the nitrile oxide-bearing carbohydrate scaffold, and the allyl group, facilitates the formation of the medium-sized rings. The cycloaddition afforded bridged isoxazolines in the cases of O-tethered allyl carbohydrate derivatives, whereas a fused isoxazoline resulted when a N(Ts)-tethered allyl derivative was used.