Synthesis of Morpholine‐2,5‐diones by Tandem Azido‐Ugi and Ugi Reactions

3,4‐Disubstituted morpholine‐2,5‐diones containing a tetrazole moiety were unexpected products of a tandem combination of azido‐Ugi and Ugi reactions. The formation of the classical products – Ugi bisamides – was not observed at all in many cases. When the simplest C1‐C3 aliphatic aldehydes were used and the reaction conditions were controlled, their isolation was possible. However, when butanal and pentanal as well as para‐substituted benzaldehydes were used, only products of post‐Ugi transformations, morpholine‐2,5‐diones, could be isolated. The latter could be synthesized either sequentially from the corresponding Ugi bisamides by post‐Ugi transformation or in a one‐pot procedure with prolonged stirring of the reaction mixture of four components – α‐aminomethyltetrazole, aldehyde, monochloroacetic acid and isocyanide. A small targeted library of 15 morpholine‐2,5‐diones containing a tetrazole moiety was obtained by a novel approach. Furthermore, these compounds were able to eliminate the N‐tert‐butyl group from the tetrazole nitrogen in the presence of acid to form the corresponding NH‐unsubstituted tetrazole derivatives of morpholine‐2,5‐diones.