Highly Enantioselective Nucleophilic Dearomatization of Pyridines by Anion-Binding Catalysis

The asymmetric dearomatization of N‐heterocycles is an important synthetic method to gain bioactive and synthetically valuable chiral heterocycles. However, the catalytic enantio‐ and regioselective dearomatization of the simplest six‐membered‐ring N‐heteroarenes, the pyridines, is still very challenging. The first anion‐binding‐catalyzed, highly enantioselective nucleophilic dearomatization of pyridines with triazole‐based H‐bond donor catalysts is presented. Contrary to other more common NH‐based H‐bond donors, this type of organocatalyst shows a prominent higher C2‐regioselectivity and is able to promote high enantioinductions via formation of a close chiral anion‐pair complex with a preformed N‐acyl pyridinium ionic intermediate. This method offers a straightforward and useful synthetic approach to chiral N‐heterocycles from abundant and readily available pyridines. Direct metal‐free access: For the asymmetric dearomatization of pyridines, only efficient metal‐catalyzed reactions have been available to date. The first organocatalytic approach with a triazole‐based H‐donor catalyst is now presented. The catalyst induces a high enantioselectivity by forming a chiral ion‐pair complex with the N‐acyl pyridinium intermediate (see picture).