Formation, rearrangement, and hydrolysis of enol esters derived from isoxazolium salts

Abstract

The hydration of N-t-butylbenzoylketenimine (2c) in water at 25°[to give the amide (7c)] occurs via acid-catalysed (at pH < 6) and pH-independent pathways. General acid catalysis by acetic acid is noted leading to the enol esters (3). The further reactions of these esters (3; R = Me, Et, or Bu^t) in aqueous solution have been investigated. In basic solution (pH > 6)(3; R¹= Me or Et) undergo HO^–-catalysed neighbouring amide group participation to give the N-acyl analogues (5), which are subsequently hydrolysed to the amides (7) at a rate which can be slower or faster than the rate of formation of (5). However when R = Bu^t, no O → N acyl group rearrangement is observed [i.e.(3c)→(5c)]; instead slow base-catalysed hydrolysis of the enol ester occurs to give (7c) directly. In acid solution all the enol esters studied are hydrolysed at much the same rate. The implications of these results for the use of the isoxazolium salts (1)[the precursors of the enol esters (3)] as reagents for peptide synthesis are commented on.