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

3,4‐Disubstituted morpholine‐2,5‐diones containing a tetrazole moiety are unexpected products of a tandem combination of azido‐Ugi and Ugi reactions. The formation of the classical products – Ugi bisamides – is not observed at all in many cases. When the simplest C1‐C3 aliphatic aldehydes are used and the reaction conditions are controlled, their isolation is possible. However, when butanal and pentanal as well as para‐substituted benzaldehydes are used, only products of post‐Ugi transformations, morpholine‐2,5‐diones, can be isolated. The latter can 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 is obtained by a novel approach. Furthermore, these compounds are 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.