Titanium-Catalyzed Stereoselective Synthesis of Spirooxindole Oxazolines

A regio- and stereoselective cyclization between isatins and 5-methoxyoxazoles has been developed using catalytic titanium(IV) chloride (10 or 20 mol %) to afford spiro[3,3'-oxindoleoxazolines] in excellent yield (up to 99%) and diastereoselectivity (dr >99:1). Substitution at the 4-position of the oxazole controls nucleophilic attack to provide either the 2-oxazoline or 3-oxazoline spirocycle with excellent (>99:1) regiocontrol.