Catalytic Enantioselective Addition of Indoles to Activated N‑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 N-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 N-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.

亲核试剂参与的吡啶（pyridines）催化对映选择性去芳构化反应，是制备高价值二氢吡啶（dihydropyridines）类化合物的直接便捷路径。现有方法多基于N-酰基吡啶鎓盐（N-acylpyridinium salts），通过在吡啶环（pyridine nucleus）的C-2/C-6位发生加成反应，生成1,2-/1,6-二氢吡啶。本文报道了该类去芳构化反应的一种替代策略：采用活化的N-苄基吡啶鎓盐（N-benzylpyridinium salts）与双功能有机催化剂（bifunctional organic catalyst）联用。亲核试剂吲哚（indole）加成至吡啶环的C-4位后，可得到光学活性的1,4-二氢吡啶作为主要产物，使该吡啶亲核去芳构化方法与此前的报道形成互补。