Work

Direct Enantioselective Construction of C3-Nitroalkylated Pyrroles by an Amine-Catalyzed Michael/Paal–Knorr Strategy

Year: 2026

Type: article

Abstract: Despite the electron-rich nature of pyrrole, the development of methods for its enantioselective C3-functionalization remains a significant synthetic challenge. In this work, a direct catalytic asymmetric synthesis of unblocked C3-nitroalkylated pyrroles has been established through a one-pot sequential process. This process involves an amine-catalyzed Michael addition of succinaldehyde to various nitroolefins, followed by an in situ Paal-Knorr cyclization with primary amines, for the rapid synthesis of a broad range of C3-nitroalkylated N-alkyl, N-aryl, and NH-pyrroles in good yields and high enantioselectivity. Broad substrate scope and functional group tolerance enable efficient access to diverse chiral pyrroles, with gram-scale synthesis and late-stage functionalization highlighting the method's practicality.

Source: The Journal of Organic Chemistry

DOI: 10.1021/acs.joc.6c02177