Nonstabilized Azomethine Ylides in the Mannich Reaction: Synthesis of 3,3-Disubstituted Pyrrolidines, Including Oxindole Alkaloids

Active methylene compounds react with in situ generated nonstabilized azomethine ylides via the domino Mannich reaction–dipolar cycloaddition to form 3,3-disubstituted pyrrolidines, including oxindole alkaloids. When the starting material possesses a single activated hydrogen, the reaction terminates at the Mannich base stage. The developed methodology was applied to a short and efficient synthesis of (±)-horsfiline and N-protected (±)-coerulescine

Reagents for Storage and Regeneration of Nonstabilized Azomethine Ylides: Spiroanthraceneoxazolidines

Nonstabilized azomethine ylides are easily trapped by anthraquinone to form stable spiro-oxazolidines, which have an unusual ability to undergo a cycloreversion in the presence of other dipolarophiles at 120–150 °C. All tested recycloadditions with carbonyl compounds and electron-poor alkenes occurred in moderate to high yields (41–92%). Moreover, increasing the reaction temperature to 210 °C made it possible to obtain adducts with low reactive dipolarophiles

Synthesis of Diketohexenoic Acid Derivatives by Alkenylation of Indoles and Pyrroles with 4‑Pyrones

A new synthesis of functionalized (<i>Z</i>)-6-hetaryl-2,4-dioxo-5-hexenoic acids based on acid-catalyzed alkenylation of indoles and pyrroles with derivatives of 5-substituted 4-pyrone-2-carboxylic acid in 37–82% yields has been developed. Coupling between isochelidonic acid and indoles followed by decarboxylation afforded biologically important (<i>E</i>)-6-indolyl-2,4-dioxo-5-hexenoic acids. These ring-opening reactions proceed with high regioselectivity through nucleophilic attack at the C-6 position of the pyrone ring. Reactions of ethyl 6-indolyl-2,4-dioxo-5-hexenoate with nucleophiles are useful for the production of different β-(indolyl)­vinyl-containing azaheterocycles

Tunable Zinc-Mediated Reductive Cyclization of Diastereomeric 3‑Nitro-4-phenacyl-2-(trihalomethyl)chromanes to Fused Pyrroline <i>N</i>‑Oxides, Pyrrolines, and Pyrrolidines

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