Synthesis of morpholines through the PPh3-catalyzed post-Ugi intramolecular umpolung oxa-Michael addition
A metal free, PPh3-catalyzed heterocyclization to form morpholines through post-Ugi intramolecular umpolung oxa-Michael addition is described. In two step synthesis, firstly the Ugi adduct is formed as the result of Ugi 4 component reaction. Then, nucleophilic phosphine catalysis allows synthesizing the heterocycles from Ugi adducts in moderate to high yields. The reaction conditions were optimized using model substrates. During the optimization studies the yield of desired products was determined by 1H NMR using the 3,4,5-trimethoxybenzaldehyde as an internal standard. Next, the scope of the process has been studied with various substrates yielding two distinct types of morpholines. All final products were purified by column chromatography and the isolated yields are reported. The structures were confirmed by 1H and 13C NMR and by high-resolution mass spectrometry (HRMS).