Enantioselective Synthesis of C–N Atropisomeric Pyrazole–Pyrroles via Asymmetric Paal–Knorr Reaction

The catalytic asymmetric construction of bis‐five‐membered C–N axially chiral scaffolds remains challenging, owing to their low rotational energy barriers. Herein, we describe a chiral phosphoric acid‐catalyzed asymmetric Paal–Knorr reaction between N ‐alkyl 5‐aminopyrazoles and 1,4‐diketones, affording ortho ‐trisubstituted C–N axially chiral pyrazole–pyrroles in high yield and excellent enantioselectivity. Moreover, the successful construction of ortho ‐trisubstituted pyrazole–pyrrole atropisomers is attributed to the strategic use of sterically bulky N ‐alkyl pyrazoles for effective stereocontrol. This protocol not only expands the repertoire of bis‐five‐membered C–N axially chiral scaffolds but also exhibits facile scale‐up and diverse late‐stage functionalizations, underscoring its synthetic utility.