Dearomatized Multifunctionalization Of N-alkyl Activated Azaarenes

Non-aromatic six-membered azaheterocyclic compounds,such as hydrogenated pyridines,quinolines and isoquinolines,have potential physiological activities and are widely used in pharmaceutical chemistry and materials science.Dearomatization of N-alkyl activated azaarenes has been proved to be an efficient and robust strategy to construct this kind of skeletons.We have successfully described an unprecedented TMG or DBU promoted one-pot multi-component Michael addition/Mannich cascade dearomatization of N-alkyl pyridinium,quinolinium and isoquinolinium salts with enaminone,which enabled the synthesis of complex and diverse bridged cyclic polycycles with multiple stereocenters in a highly regio-and diastereoselective manner with high synthetic efficiency.In addition,we realized the step-controlled dearomative bi-and trifunctionalization of quinolinium salts.These transformations not only opened up a new reaction mode of these N-activated azaarenes to achieved the maximization of the reactive sites of pyridinium,quinolinium and isoquinolinium salts,but also were endowed with the apparent features including high synthetic efficiency,short reaction time,mild conditions and simple operation.We have also successfully developed the diastereoselective dearomatizations of pyridinium,quinolinium and isoquinolinium salts when enimine hydrochloride as another binucleophile,enable to complete similar transformations in a highly regio-and diastereoselective manner with high synthetic efficiency.Remarkably,we realized the step-controlled dearomative bi-and trifunctionalization of isoquinolinium salts.The presence of an imine group in the target molecules has provided a versatile platform for further functionalization.