Ring-Opening Reactions\nof Imidazolidines and Hexahydropyrimidines\nwith Grignard Reagents

We\nherein report an unprecedented ring-opening of unstrained\ncyclic\naminals such as imidazolidines and hexahydropyrimidines by the use\nof Grignard and cuprate reagents to give secondary sulfonamides bearing\ndiversely substituted tertiary amines in the β- or γ-position.\nThis synthetic procedure can be carried out in a one-pot fashion without\ncollateral reactions that are commonly associated with sp<sup>3</sup>-organometallic multicomponent Mannich-type reactions, indicating\nthe fundamental role of sulfonamide protection of the second nitrogen\natom in the generation of the cyclic aminal and in the ring-opening\nprocess. Computational density functional theory (DFT) data point\nto the formation of a transient iminium ion intermediate, in which\nthe Lewis acidity of the cationic component of the organometallic\nreagent triggers the ring-opening process by coordination. The presented\nmethod allows the nucleophilic decoration of diamines including those\nbearing an adjacent chiral center to the tertiary amine not easily\nachievable by means of alternative standard synthetic procedures.