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We have described a simple, convenient, and high‐yielding one‐pot synthesis of novel azo chromene derivatives via a three‐component reaction of various azo aldehydes with dimedone and malononitrile using 10 mol% of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as catalyst and ethanol as solvent at reflux condition. All the synthesized compounds have been characterized using Fourier‐transform infrared spectroscopy (FT‐IR), 1H NMR, 13C NMR, and HR‐MS spectra and molecular docking was performed to explore new inhibitors of human placental aromatase cytochrome P450 and cyclooxygenase‐2 enzymes. Of all the compounds docked, compound (E)‐2‐amino‐4‐(4,4‐dimethyl‐2,6‐dioxocyclohexyl)‐6‐((3‐methoxyphenyl)diazenyl‐4H‐chromene‐3‐carbonitrile (4o) showed good binding affinity with the active site of human placental aromatase cytochrome P450 enzyme (PDB: 3EQM) with inhibition constant (Ki) 1.66 nM and compound 4o also showed good binding affinity with the active site of cyclooxygenase‐2 enzyme (PDB: 6COX) with inhibition constant (Ki) 367.17 pM. In vitro anti‐cancer activity studies against MCF‐7 cells were also performed for compounds 4o, anastrozole and celecoxib. Compound 4o showed an effective cytotoxicity at 19.8 μg/ml compared to anastrozole and celecoxib (24.7 and 26.2 μg/ml). [ABSTRACT FROM AUTHOR]

Abstract: A catalyst‐dependent chemoselective one‐carbon insertion of diazo compounds into the C−C or C−H bonds of 1,3‐dicarbonyl species is reported. In the presence of silver(I) triflate, diazo insertion into the C(=O)−C bond of the 1,3‐dicarbonyl substrate leads to a 1,4‐dicarbonyl product containing an all‐carbon α‐quaternary center. This reaction constitutes the first example of an insertion of diazo‐derived carbenoids into acyclic C−C bonds. When instead scandium(III) triflate was applied as the catalyst, the reaction pathway switched to formal C−H insertion, affording 2‐alkylated 1,3‐dicarbonyl products. Different reaction pathways are proposed to account for this powerful catalyst‐dependent chemoselectivity. [ABSTRACT FROM AUTHOR]

via condensation of dimedone with aromatic aldehydes (13 examples) [ABSTRACT FROM AUTHOR]