Enantioselective synthesis of α-(3-pyrrolyl)methanamines with an aza-tetrasubstituted center under metal-free conditions†

Construction of a chiral methanamine unit at the C3 position of pyrrole is highly desirable; nevertheless, it remains challenging due to its intrinsic electronic properties. Herein, we present an operationally straightforward and direct asymmetric approach for accessing α-(3-pyrrolyl)methanamines under benign organocatalytic conditions for the first time. The one-pot transformation proceeds smoothly through an amine-catalyzed direct Mannich reaction of succinaldehyde with various endo-cyclic imines, followed by a Paal–Knorr cyclization with a primary amine. Several N–H/alkyl/Ar α-(3-pyrrolyl)methanamines with an aza-tetrasubstituted center have been synthesized with good yields and excellent enantioselectivity.