Abstract
Facile procedures for the construction of fused indole-containing heteropolycycles 1a-f and 2a-c have been developed. The methodology involves Friedel-Crafts cyclialkylations of heteoraryl alkanols in the presence of both Bronsted (PPA) and Lewis (AlCl3/CH3NO2) acid catalysts. The starting alkanols 6a-f and 12a-c were smoothly obtained both by reactions of the corresponding carboxylic acid esters and the corresponding ketones with Grignard reagents. Overall, this approach allows for easy and efficient access to polycyclic indoles from easily synthesized precursors.
Highlights
Heteropolycycles containing indole moieties possess a wide diversity of biological activities1 beside their presence in a large array of pharmaceuticals2 and natural products.3 For example, 7,8-dihydro-6H-indolo[2,1-a][2]benzazepine (1)4 and 6,7-dihydroindolo[2,1-a]isoquinoline (2)5-7 have unique nitrogen-containing tetracyclic8 structures (Scheme 1)
Synthesis of cyclialkylating alcohols The heteroaryl alkanols required for this work (6a-f and 12a-c) were all obtained starting from the accessible37 7-methyl-2-phenyl-1H-indole (3) via three different pathways as formulated in Scheme 2: Path 1, included the base catalyzed N-alkylation of 3 with ethyl 3bromopropanoate (4) to give ethyl 3-(7-methyl-2-phenyl-1H-indol-1-yl)propanoate (5)
Simple and facile synthetic pathways for the construction of different indole-based substituted heteropolycycles via Friedel-Crafts cyclialkylation of heteroarylalkanols (6a-f and 12a-c) catalyzed by AlCl3/CH3NO2 and PPA
Summary
Heteropolycycles containing indole moieties possess a wide diversity of biological activities1 beside their presence in a large array of pharmaceuticals2 and natural products.3 For example, 7,8-dihydro-6H-indolo[2,1-a][2]benzazepine (1)4 and 6,7-dihydroindolo[2,1-a]isoquinoline (2)5-7 have unique nitrogen-containing tetracyclic8 structures (Scheme 1). Cyclialkylations of alcohols 6a-f were conducted in the presence of AlCl3/CH3NO2 and PPA catalysts under the conditions outlined in Table 2 to give the title benzazepines 1a-f (Table 2 and Scheme 3).
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