Photocatalyst-Free Chiral Phosphoric Acid-Catalyzed Enantioselective Minisci-Type Alkylation of N-Heteroarenes

In this study, we present an efficient radical approach for the enantioselective Minisci-type alkylation of N-heteroarenes, using chiral phosphoric acid (CPA) as a catalyst under mild conditions, without the need for metals, photocatalysts, and other additives. Prochiral alpha-aminoalkyl radicals generated from RAEs were successfully introduced to N-heteroarene derivatives, including pyridine, quinoline, and isoquinoline, resulting in a range of valuable chiral alkylated N-heteroarenes with secondary amines in high yields and good to excellent enantioselectivities (up to 98 % ee). The chiral phosphoric acid catalyst not only activates the substrate and induces asymmetry but also facilitates essential electron transfer processes.