• isocyanide
• kinetic studies
• mechanism
• morpholine
• multicomponent reaction
• optimization
• oxazoline
• passerini reaction
• titanium

The object of the present work has been a beta-alkoxy isocyanide-based Passerini-like multicomponent reaction promoted by Ti(OiPr)4 and leading to functionalized morpholines. In the presence of a stoichiometric amount of Ti(OiPr)4 and a strong base such as tBuLi, the reaction of a 2-oxazoline, an aromatic Grignard reagent and an aromatic nitrile yields a functionalized morpholine as the main product after hydrolisis. The optimization of this multicomponent reaction, with the aim to increase the yield of the reaction itself and to develop a general procedure for the synthesis of differently functionalized morpholines, has been carried out. Moreover, a preliminary study of the reaction mechanism has been realized and a hypothetical key reaction intermediate has been proposed. Following the optimized standard procedure, additional reagents expected to react in a predictable way with the intermediate have been used, with the aim of trapping the supposed intermediate into products that fit the mechanistic hypothesis. Most of the reactions presented in the present work are expected to share the same reaction intermediate, and as a whole represent an interesting synthetic cluster of related multicomponent reactions.