Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

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