An unprecedented base-promoted multi-component one-pot dearomatization of N-alkyl activated azaarenes was developed, which enabled the synthesis of complex and diverse bridged cyclic polycycles with multiple stereocenters in a highly regio- and diastereoselective manner. Besides, we realized the step-controlled dearomative bi- and trifunctionalization of quinolinium salts. These transformations not only achieved the maximization of the reaction sites of pyridinium, quinolinium and isoquinolinium salts to enhance structural complexity and diversity, but also opened up a new reaction mode of these N-activated azaarenes. A unique feature of this strategy is the use of easily accessible and bench-stable N-alkyl activated azaarenes to provide maximum reactive sites for dearomative cascade cyclizations. In addition, the salient characteristics including high synthetic efficiency, short reaction time, mild conditions and simple operation made this strategy particularly attractive.

Bridged polycycles are privileged molecular skeletons with wide occurrence in bioactive natural products and pharmaceuticals. Therefore, they have been the pursing target molecules of numerous chemists. The rapid and convenient generation of sp³-rich complex three-dimensional molecular skeletons from simple and easily available aromatics has made dearomatization a highly valuable synthetic tool for the construction of rigid and challenging bridged rings. This review summarizes the-state-of-the-art advances of dearomatization strategies in the application of bridged ring formation, discusses their advantages and limitations and the in-depth mechanism, and highlights their synthetic value in the total synthesis of natural products. We wish this review will provide an important reference for medicinal and synthetic chemists and will inspire further development in this intriguing research area.

A TfOH-catalyzed highly diastereoselective Michael addition/ketalization sequence of 3-hydroxyoxindoles and ortho-hydroxychalcones was developed, leading to biologically important bridged ketal spirooxindoles in moderate to excellent yields. Moreover, some chemical transformations were carried out to further extend the structural complexity and diversity.