Efficient Synthesis of Enantioenriched Isoxazoles by Chirality Transfer in Gold-Catalyzed Cyclization/Methylene-Group Transfer Followed by Carbonyl Ene Reaction

Enantioenriched isoxazoles having a chiral side chain at the 4-position were efficiently synthesized by chirality transfer in a gold-catalyzed cyclization/intermolecular methylene-transfer sequence followed by a carbonyl ene reaction. The chiral information of the enantioenriched O-propargylic oximes was completely retained during the gold-catalyzed reaction. The subsequent carbonyl ene reaction between the resulting 4-methylenated isoxazoline and glyoxylates proceeded with excellent levels of chirality transfer by using BF₃·OEt₂ as a Lewis acid. According to the relationship of absolute configuration between the starting propargylic oxime and the obtained alcohol having an isoxazole, the carbonyl ene reaction proceeded in an endo manner.