Nikolay S. Zimnitskiy

Simple and convenient chemoselective methods for the synthesis of 4-styryl-6-polyfluoroalkylpyrimidines based on the Pinner-type condensation of 1-polyfluoroalkyl-3-styryl-1,3-diketones with S-alkylisothiourea, guanidines and amidines have been developed. The cyclocondensation of 1-polyfluoroalkyl-3-styryl-1,3-diketones with S-alkylisothiourea salts in an EtOH/AcOH (2:1) solution in the presence of NaOAc under reflux for 8–12 h leads to 2-alkylsulfanyl-4-styryl-6-polyfluoroalkylpyrimidines in 56–89% yields. A similar reaction involving these enediones with guanidine or amidine salts in the presence of B(OMe)₃ in MeCN under reflux for 1–5 h affords the corresponding 4-styryl-6-polyfluoroalkylpyrimidines in 57–96% yields. The high reactivity of the 1,3-dicarbonyl fragment of 1-polyfluoroalkyl-3-styryl-1,3-diketones towards 1,3-N,N-dinucleophiles is due to charge control of the reaction, which is in good agreement with the DFT calculation data. Received: 04 February 2026 Accepted after revision: 13 April 2026 Accepted Manuscript online: 13 April 2026 © . Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Chemoselective methods for the synthesis of 1,5-benzodiazepine derivatives have been developed from 1-polyfluoroalkyl-3-styryl-1,3-diketones and o-arylenediamines or 2-aminothiophenol. When the reaction was carried out in MeOH or MeCN at room temperature, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepines were obtained in 36–90% yields as a result of the addition of 1,2-diamine to the α,β-unsaturated ketone fragment of the enedione. A similar reaction of 1-CF₃-3-styryl-1,3-diketones in MeOH at −18 °C led to 2-hydroxy-4-styryl-2,3-dihydro-1H-1,5-benzodiazepines in 57–87% yields as a result of the addition of 1,2-diamine to the 1,3-dicarbonyl fragment of the enedione. Dehydration of 2-hydroxy-4-styryl-2,3-dihydro-1H-1,5-benzodiazepines with trifluoroacetic acid in CH₂Cl₂ at room temperature gave the corresponding 3H-1,5-benzodiazepines in 73–96% yields. 2-Difluoromethyl-substituted 3H-1,5-benzodiazepines can be synthesized directly from the corresponding enediones and o-arylenediamines in MeOH at room temperature in one step in 76–95% yields. 2-Aminothiophenol reacts with 1-polyfluorolalkyl-3-styryl-1,3-diketones at reflux in EtOH to form 2,3,4,5-tetrahydro-1,5-benzothiazepines in 24–36% yields, whereas the reaction with aminophenol stops at the enaminone stage.

A regio- and stereoselective method for the synthesis of spiro[indolin-3,2′-pyrrolidine]-2-ones based on the [3 + 2] cycloaddition of azomethine ylides, generated in situ from isatins and proteinogenic α-amino acids, and (E)-5-arylpent-4-ene-1,3-diones under reflux in methanol within 12 h in 28–91% yields has been developed. A number of representative examples of spiro[indolin-3,2′-pyrrolidine]-2-ones have been studied for cytotoxic activity against HeLa cervical cancer cell line and human dermal fibroblasts (HDF) by the MTT assay. Every investigated compound has shown cytotoxic activity against HeLa cells (IC₅₀ 0.24–38.43 μM), while some of them have also shown low cytotoxicity against HDF cells (IC₅₀ 100.08–7821.27 μM). A preliminary structure–activity relationship (SAR) correlations have been made.

Reductive cyclization of trans,trans- and trans,cis-isomers of the 2-CF3-substituted 3-nitro-4-phenacylchromanes with Zn-based reductive systems, depending on the conditions, affords 4-CF3-substituted 1,3a,4,9b-tetrahydrochromeno-[3,4-b]-pyrrole 3-oxides, 1,3a,4,9b-tetrahydrochromeno-[3,4-b]-pyrroles, or 1,2,3,3a,4,9b-hexahydrochromeno-[3,4-b]-pyrroles in good yields without changing the relative configuration of the pyran ring. A similar process involving the 2-CCl3-substituted 3-nitro-4-phenacylchromanes is accompanied by reductive dehalogenation to form the corresponding 4-dichloromethyl-substituted fused chromanes along with the 3-(2-hydroxyaryl)-2-(2,2-dichlorovinyl)-5-phenyl-2H-pyrroline 1-oxides as pyran ring opening products. The structure and relative configuration of the obtained products was reliably confirmed by X-ray diffraction analysis and 2D NMR spectroscopy.

For the first time, a review has been conducted on the methods for the synthesis, as well as on the chemical, physical and biological properties, of 5-arylpent-4-ene-1,3-diones (hemicurcuminoids).

The AgOAc-catalysed reaction of 3-nitro-2-phenyl-2H-chromenes with stabilized azomethine ylides generated from the imines based on methyl glycinate and arylaldehydes leads to a mixture of endo and endo’ isomers of the corresponding chromeno[3,4-c]pyrrolidines in a ratio of 2.0–2.3:1 in 85–93% total yields as a result of a Michael addition/Mannich reaction sequence. In a similar reaction involving 2-trifluoromethyl-3-nitro-2H-chromenes, only endo chromeno[3,4-c]pyrrolidines are formed in 85–94% yields. 3-Nitro-2-(trichloromethyl)-2H-chromenes under the same conditions react with these azomethine ylides to give the corresponding Michael adducts as individual anti-isomers with the cis,trans-configuration of the chromane ring in 40–67% yields. Some 4-CF₃-substituted chromano[3,4-c]pyrrolidines exhibited high cytotoxic activity against HeLa human cervical carcinoma cells.

A regioselective one-pot method for the synthesis of 1-ethyl 2,4-dihydrochromene[3,4-c]pyrroles in 63–94% yields from available 2-phenyl-, 2-trifluoro(trichloro)methyl- or 2-phenyl-2-(trifluoromethyl)-3-nitro-2H-chromenes and ethyl isocyanoacetate through the Barton–Zard reaction in ethanol at reflux for 0.5 h, using K₂CO₃ as a base, has been developed.

One-pot stereoselective methods for the synthesis of hexahydro-9 H -benzo[ c ]chromen-9-ones and hexahydro-1 H ,6 H -chromeno[6,5- c ]chromen-1-ones have been developed.