Palladium-Catalyzed One-Pot Three- or Four-Component Coupling of Aryl Iodides, Alkynes, and Amines through CN Bond Cleavage: Efficient Synthesis of Indole Derivatives

• Published in: Chemistry : a European journal 2014-02, Vol.20 (9), p.2605-2612
• Main Authors: Hao, Wei, Geng, Weizhi, Zhang, Wen-Xiong, Xi, Zhenfeng
• Format: Article
• Language: English
• Subjects: Alkynes; Alkynes - chemistry; Amines; Amines - chemistry; Aromatic compounds; Catalysis; cleavage reactions; Derivatives; Heterocyclic Compounds - chemistry; Indoles; Indoles - chemical synthesis; Indoles - chemistry; Iodides; Iodides - chemistry; Joining; Ligands; Molecular Structure; multicomponent reactions; palladium; Palladium - chemistry; Phosphines - chemistry; Synthesis; synthetic methods
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201304215

An efficient synthesis of N‐substituted indole derivatives was realized by combining the Pd‐catalyzed one‐pot multicomponent coupling approach with cleavage of the C(sp3)N bonds. Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene–phosphine ligand showed high efficiency. A variety of aryl iodides, including cyclic and acyclic tertiary amino aryl iodides, and substituted 1‐bromo‐2‐iodobenzene derivatives could be used. Both symmetric and unsymmetric alkynes substituted with alkyl, aryl, or trimethylsilyl groups could be applied. Cyclic secondary amines such as piperidine, morpholine, 4‐methylpiperidine, 1‐methylpiperazine, 2‐methylpiperidine, and acyclic amines including secondary and primary amines all showed good reactivity. Further application of the resulting indole derivatives was demonstrated by the synthesis of benzosilolo[2,3‐b]indole. All in one: Efficient synthesis of N‐substituted indole derivatives was realized by combining a Pd‐catalyzed one‐pot multicomponent coupling approach with the cleavage of C(sp3)N bonds (see scheme). Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene–phosphine ligand (1) showed high efficiency.