1,3,5‐Oxadiazine Framework by Oxygen vs. Nitrogen Trapping of an N‐Acyliminium Ion Derived from N,O‐bis‐TMS Pyroglutamic Acid

Abstract

AbstractWe report that the reaction of N,O‐bis‐TMS pyroglutamic acid with aldehydes, under basic or acid catalysis leads to O‐bis‐TMS adducts. Treatment of these N,O‐acetals by TfOH affords azalactones or N,N′‐substituted methylene‐bis‐pyroglutamic acids from the trapping of N‐acyliminium species, respectively, with oxygen or nitrogen atom intramolecularly versus intermolecularly. Anodic oxidation of the amido acids, followed by diastereoselective oxa‐cyclisation of new N‐acyliminium salts, provides exclusively fused meso‐1,3,5‐oxadiazines with the stereochemistry secured by X‐ray analysis. The reactivity of these skeletons under both alkaline and acid conditions was also envisioned and discussed.