Unexpected isomerization of oxetane-carboxylic acids

Abstract

We unexpectedly discovered that popular oxetane-carboxylic acids are intrinsically unstable. They easily isomerize into lactones under storage at rt, or under slight heating. Chemists should keep in mind the high instability of these common molecules, as this could dramatically affect the reaction yields and lead to negative results (especially in those reactions that require heating).

Biphasic Electrosynthesis of 2-Isoxazol(in)e-3-carboxylates: Reaction Optimization from Milligram to Hectogram Scale

“…7 In addition, 4 is an isoxazoline derived from the anticonvulsant carbamazepine, demonstrating the application of dipolar cycloadditions in the late-stage functionalization of pharmaceuticals. 8,9 Common synthetic routes for accessing isoxazolines and isoxazoles involve the in situ formation of highly reactive nitrile oxides from N-hydroximidoyl halides followed by their 1,3dipolar cycloaddition. 10,11 The major drawback of this synthetic protocol is the necessity for equimolar amounts of oxidants, large quantities of hazardous halogenating agents, and harsh reaction conditions.…”