A Union of Distinct Azolium Salts Toward Stereoselective Synthesis of Tertiary Amine Cage Frameworks

The tertiary amine-based cage molecules are high-value intricate synthetic targets and their succinct stereoselective synthesis with broad substrate generality remains rare. Herein, we report for the first time the union of two distinct readily available azolium salts as an efficient synthetic platform to access natural products like tertiary amine cage frameworks under mild conditions. The strategy combines the masked nucleophilic and electrophilic properties of isoquinolinium salts and pyridinium salts, respectively, and avails double dearomatization guided inverse electron demand (4+2) or (3+2) annulation in a highly regio- and diastereoselective manner to materialize the nitrogen cage motifs including the aza-polycyclic core of hetisine-type alkaloids in high yields (50 examples). To streamline further, we delineated a five-component as well as a four-component one-pot sequential addition strategy without compromising the selectivity, emphasizing the efficient utilization of resources and the pot economy. Our methodology harvests two new rings and four new bonds in a single operation and transforms from flat-aromatic compounds into structurally unprecedented three-dimensional architectures with contiguous stereocenters as a single diastereomer.