Ring-Opening Reactions of Imidazolidines and Hexahydropyrimidines with Grignard Reagents

We herein report an unprecedented ring opening of unstrained cyclic aminals such as imidazolidines and hexahydropyrimidines by the use of Grignard and cuprates reagents to give primary sulfonamides bearing diversely substituted tertiary amines in beta- or gamma-position. This synthetic procedure can be carried out in a one-pot fashion without the collateral reactions that are commonly associated with sp3-organometallic multicomponent Mannich type reactions, indicating the fundamental role of the sulfonamide protection of the second nitrogen atom in the generation of the cyclic aminal and in the ring-opening process. Computational DFT data point to the formation of a transient iminium ion intermediate in which the Lewis acidity of the cationic component of the organometallic reagent triggers the ring-opening process by coordination. The presented method allows the nucleophilic decoration of diamines including those bearing an adjacent chiral center to the tertiary amine not easy achievable by means of alternative standard synthetic procedures.