Catalytic Enantioselective Addition of Indoles to Activated <i>N</i>‑Benzylpyridinium Salts: Nucleophilic Dearomatization of Pyridines with Unusual C‑4 Regioselectivity

The catalytic enantioselective dearomatization of pyridines with nucleophiles represents a direct and convenient access to highly valuable dihydropyridines. Available methods, mostly based on <i>N</i>-acylpyridinium salts, give addition to the C-2/C-6 of the pyridine nucleus, rendering 1,2-/1,6-dihydropyridines. Herein, we present an alternative approach to this type of dearomatization reaction, employing activated <i>N</i>-benzylpyridinium salts in combination with a bifunctional organic catalyst. Optically active 1,4-dihydropyridines resulting from the addition of the nucleophile (indole) to the C-4 of the pyridine nucleus are obtained as major products, rendering this method for nucleophilic dearomatization of pyridines complementary to previous approaches