Enantioselective Construction of Tetrahydro‐α‐Carbolines via Organocatalytic Friedel‐Crafts Alkylation/N‐Hemiacetalization of 2‐Aminoindoles with Enals

• Published in: European journal of organic chemistry Vol. 28; no. 14
• Main Authors: Liu, Xiaochun, Ding, Xiang‐Feng, Liu, Yang‐Zi, Deng, Wei‐Ping
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 07.04.2025
• Subjects: Aldehydes; Alkylation; Asymmetric catalysis; Biological activity; Enantiomers; Nitrogen-containing fused ring; Organocatalysis; Tetrahydro-α-carboline
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202401431

An efficient organocatalytic asymmetric Friedel‐Crafts alkylation/N‐hemiacetalization reaction of 2‐aminoindoles with α,β‐unsaturated aldehydes was developed. By incorporating an amino group at the C2 position of indole, the nucleophilicity of the C3 position of indole and the amino group were leveraged to generate an enamine‐type ternary synthon. This approach enabled the construction of a range of chiral tetrahydro‐α‐carboline skeletons with potential biological activity, delivering moderate to excellent yields (46–83 %) and achieving outstanding enantioselectivity (up to 99 % ee). An efficient organocatalytic asymmetric Friedel‐Crafts alkylation/N‐hemiacetalization reaction of 2‐aminoindoles with α,β‐unsaturated aldehydes has been established. This mild and effective synthetic method exhibits a wide substrate scope, facilitating the synthesis of chiral tetrahydro‐α‐carbolines with potential biological activity.