Different Behavior of 2-Substituted 3-Nitro-2H-chromenes in the Reaction with Stabilized Azomethine Ylides Generated from α-Iminoesters

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-12, Vol.27 (24), p.8983
• Main Authors: Kochnev, Ivan A., Barkov, Alexey Y., Simonov, Nikita S., Ulitko, Maria V., Zimnitskiy, Nikolay S., Korotaev, Vladislav Y., Sosnovskikh, Vyacheslav Y.
• Format: Article
• Language: English
• Subjects: 3-nitro-2H-chromenes; Adducts; azomethine ylides; Cervical cancer; Cervical carcinoma; Cervix; chromeno[3,4-c]pyrrolidines; Cytotoxicity; Imines; Isomers; Michael addition/Mannich reaction sequence; Spectrum analysis; Substitutes
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27248983

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.