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Herein, we describe a novel reaction between C-2-substituted indoles and 2-nitroacetophenones leading to a variety of indole-containing heterocyclic scaffolds. At 60 °C in AcOH with H 2 SO 4 as catalyst, C-2 aryl indoles give 3-(2-nitrovinyl)-indoles with high Z or E geometric selectivity depending on the type of substrate utilized. These compounds undergo an electrocyclization process in a sealed vial in a microwave apparatus in DMF at 250 °C to give benzo[ a ]carbazoles and naphtho[2,1- a ]carbazoles depending on whether the C-2 aromatic moiety is phenyl or naphthyl. Utilization of 2-methylindoles in the reaction with 2-nitroacetophenones and performing the reaction in a sealed vial in a microwave apparatus in AcOH at 200 °C leads to 1-hydroxy-β-carbolines. Selected compounds from each scaffold were tested for antiproliferative activities against MDA-MB-231 triple-negative breast cancer cells under normoxic and hypoxic conditions, and three compounds belonging to the 3-(2-nitrovinyl)-indole and 1-hydroxy-β-carboline series were identified to have single-digit micromolar IC 50 values.

A highly diastereoselective tandem reaction of 2'-nitrochalcones is reported, involving Michael addition and a subsequent ipso -substitution of the nitro group to produce 1-tetralones with two contiguous chiral centers. A related annulation reaction of 2'-nitrochalcones with potassium cyanide affording 1-indanones with a C3-quaternary chiral center is also demonstrated.

Unusual cascade transformation involving ring opening and 1,2-alkyl shift was observed upon the reduction of 4' H -spiro[indole-3,5'-isoxazoles] or 2-(3-oxoindolin-2-yl)acetonitriles with sodium borohydride. This reaction allowed for expeditious and highly efficient preparation of 2-(1 H -Indol-3-yl)acetamides with antiproliferative properties.

Base-assisted transformations of 2-(3-oxoindolin-2-yl)acetonitriles were investigated. Unexpectedly, attempted reactions of substrates possessing nonprotected nitrogen atoms were accompanied by unusual extrusions of 2-arylacetonitriles, followed by a 1,2-aryl shift to afford 3-hydroxyindolin-2-ones. On the other hand, the reactions for N -alkyl derivatives of oxoindolines took the expected route by only providing 1,2,3,3a,4,8b-hexahydropyrrolo[3,2- b ]indoles.

An efficient and straightforward Brønsted-acid mediated cascade process was developed, involving cyclization of readily available β-ketonitriles into 2-aminofurans, and their subsequent recyclization into 2-(1 H -indol-2-yl)acetamides is developed. This synthetic route opens a new avenue for an expeditious assembly of various isotryptamine derivatives for medicinal chemistry.

Recently discovered reactivity of nitrostyrenes in phosphorous acid to facilitate the diastereoselective [4 + 1]-cycloaddition of indoles in combination with unusual oxazoline ring cleavage and subsequent 1,2-alkyl shift afforded stereochemically defined 2-(3-oxoindolin-2-yl)-2-arylacetonitriles as sole products.

An acid-assisted [4 + 1]-cycloaddition of indoles with nitrostyrenes affords 4' H-spiro[indole-3,5'-isoxazoles] in a diastereomerically pure form. Several of these spirocyclic molecules exhibit promising anticancer activity by reducing viability and inducing differentiation of neuroblastoma cells.

A strain-release-driven, cation-templated intramolecular nucleophilic addition of tethered alkoxides to prochiral cyclopropenes is described. Employment of chiral β- and γ-amino alkoxides allowed for highly diastereoselective assembly of a small series of enantiopure cyclopropane-fused oxazepanones. It was shown that the chiral center at C-4 plays a crucial role in controlling desymmetrization of the cyclopropenyl moiety, instigated by a profound potassium-templated effect. The preliminary biological activities of the new cyclopropane-fused medium heterocycles against Gram-positive bacteria, Gram-negative bacteria, mycobacteria, cancer cells, and fungus were evaluated.

Indolo[3,2-c]quinolones have been efficiently synthesized via an acid-mediated, one-pot, three-component condensation of arylhydrazines, o-aminoacetophenones, and triazines or nitriles. The synthetic application of this method is showcased by the concise synthesis of isocryptolepine alkaloid and a series of its synthetic analogues with demonstrated cancer cell antiproliferative activities.