Metalation of Isoxazolyloxazolines, a Facile Route to Functionally Complex Isoxazoles: Utility, Scope, and Comparison to Dianion Methodology

2-(5'-Alkylisoxazol-4 '-yl)-Δ2-oxazoline was metalated at the C-5’ alkyl group, and the lithio anion was quenched with a variety of electrophiles. Alkyl halides, aldehydes, and acylpyridinium salts were used as electrophiles. The lithio anion was oxygenated with MOOPH or N-(phenylsulfonyl)oxaziridene. The isoxazolyloxazoline system was converted to the isoxazolyl carboxylic acid, aldehyde, ketone, and chiral oxazoline. The isoxazolyloxazoline was formed, metalated, and deprotected in synthetically useful yields and represents a facile entry into functionally complex isoxazoles. To determine the necessity of the oxazoline protection/deprotection scheme, dianions of isoxazole-4-carboxylic acids were studied. The dianion method was found to be more efficient for simple alkyl halides, but limited in scope.