Beilstein J. Org. Chem.2018,14, 2907–2915, doi:10.3762/bjoc.14.269
–C bond forming reaction [57] and three-component reactions of aromatic aldehydes, 3-(1H-indol-3-yl)-3-oxopropanenitrile and malononitrile [58][59], 2-acetylpyridine [60] or 3-amino-2-enones [61]. Incidentally, the indole scaffold is found in several natural products and bioactive synthetic compounds
-oxopropanenitriles 3 were synthesized from the reaction of indoles 1 and 2-cyanoacetic acid (2) in acetic anhydride under heating conditions (Scheme 1) [73].
Subsequently the one-pot four-component reaction of 3-(1H-indol-3-yl)-3-oxopropanenitrile (3a), 4-chlorobenzaldehyde (4f), cyclododecanone (5a) and ammonium
8.16 ppm (J = 3.0 Hz) due to 2′-CH proton.
A persuasive mechanism to justify the formation of indole–cyclododeca[b]pyridine-3-carbonitrile hybrid 7f is depicted in Scheme 2. Initially, the Knoevenagel condensation of 3-(1H-indol-3-yl)-3-oxopropanenitrile (3a) and 4-chlorobenzaldehyde (4f) leads to the
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Graphical Abstract
Figure 1:
Examples of biologically important cycloalkyl-fused pyridines.