Imines with rare α-heteroatom substituted amine components generated the Staudinger/aza-Wittig tandem reaction and their application in multicomponent reactions.

A series of structurally diverse α-heteroatom substituted methyl azides (XCHN, where X = phthalimidoyl, benzotriazolyl, arylsulfanyl, aryloxy, alkoxy) have been prepared and evaluated for the generation of imines the Staudinger/aza-Wittig tandem reaction with aldehydes and triphenylphosphine. The obtained imines were successfully introduced into four types of multicomponent reactions: the Staudinger β-lactam synthesis with diazo carbonyl compounds, the Castagnoli-Cushman reaction with cyclic anhydrides, and the Ugi and azido-Ugi reactions with isocyanides and carboxylic acids or TMS-azides. These transformations allowed the preparation of four-to-seven-membered lactams, acyclic bisamides and 5-(aminomethyl)-1-alkyltetrazoles with a complex and previously poorly accessible periphery. Moreover, it was demonstrated that phthalimide derivatives can be deprotected to afford medicinally relevant -aminomethyl lactams.