부산대학교 도서관

A unique reactivity pattern in which the catalyst and the reactant motifs are joined together in a substrate is investigated using density functional theory calculations. The versatile triaza CN3 functionality in bicyclic guanidines is combined with a diversity of functional groups about the molecular scaffold which, upon addition of N-nucleophiles, transfers the substrate to its hitherto unreported tricyclic analogues. Unprecedentedly, the guanidine/guanidinium dyad advances the reaction by displaying all possible chemical functionalities, including Brønsted acid–base and Lewis acid–base activation modes. This study presents the first example of a guanidine-catalyzed thioamidation reaction. Furthermore, it evidences the first participation of guanidinium’s Lewis acid activation in a cyclization reaction. In addition to the several mono- and bifunctional activation modes, two rare examples of Lewis acid interaction were observed, which provides important mechanistic points. The first one in the thioamidation step suggests the preference for stepwise elimination of MeSH over the alternative concerted mechanisms. However, the second one in the N-Michael addition step provides a new insight into the Lewis acidity activation mode of guanidinium species. The interaction first traps the side branch of the substrate containing the nucleophilic motif and then, by positioning the anionic nucleophile and the Michael acceptor site in close proximity, navigates the regioselective N-Michael addition.