1,4‐Dearomatization of Pyridines and Quinolines Enabled by the Carbodication Lewis Acid

1,4-Dihydropyridines (DHPs) are valuable compounds in medicinal chemistry and organic synthesis. The most straightforward pathway for preparing 1,4-DHPs is the direct 1,4-reduction of pyridines and quinolines. However, existing strategies are not effective for pyridines with electron-withdrawing substituents at the C2 position. To address this long-standing issue, a new strategy has been developed that utilizes underexplored carbodications as the Lewis acids to activate pyridines. For the first time, pyridines with -CN and -ester substituents at the C2 position have been successfully converted to 1,4-DHPs through direct reductive dearomatization in exclusive C4 selectivity. The potential utility of this 1,4-DHP synthetic protocol is demonstrated with C5-bromination, C5-trifluoromethylation, C5-deuteration, and C4-deuteration of pyridines using the in situ generated 1,4-DHPs as key intermediates.