Arylidenemalononitriles as Versatile Synthons in Heterocyclic Synthesis

Background: Objective: Objective: biological science.: Background: Arylidenemalononitriles are valuable synthons for the construction of a variety of novel complex heterocyclic motifs, fused heterocycle derivatives and spirocyclic compounds. They are versatile chemical intermediates and have increasing applications in industry, agriculture, medicine, Objective: The aim of this review is to highlight the preparation methods and reactions of arylidenemalononitriles in the synthesis of various heterocyclic compounds. Conclusion: n this review, we have presented the application of arylidenemalononitriles to construct a variety of heterocycles. Various catalysts for the preparation of arylidnemalononitriles have been described.

Direct access to spirocycles by Pd/WingPhos-catalyzed enantioselective cycloaddition of 1,3-enynes

Spirocycles play an important role in drug discovery and development. The direct, catalytic, and enantioselective synthesis of spirocycles from readily available starting materials and in an atom economic manner remains a highly sought-after task in organic synthesis. Herein, an enantioselective Pd-hydride-catalyzed cycloaddition method for the synthesis of spirocyclic compounds directly from two classes of commonly available starting materials, 1,3-enynes and cyclic carbon−hydrogen (C−H) bonds, is reported. The reactions employ a chiral Pd/WingPhos catalyst to both suppress the formation of bis-allenyl by-products and control the stereoselectivity. 1,3-Enynes are used as dielectrophilic four-carbon units in the cycloaddition reactions, which also enables an enyne substrate-directed enantioselectivity switch with good levels of stereocontrol. The present spirocycle synthesis tolerates a broad range of functional groups of 1,3-enyne substrates, including alcohols, esters, nitriles, halides, and olefins. A variety of diverse cyclic nucleophiles, including pharmaceutically important heterocycles and carbocycles, can be flexibly incorporated with spiro scaffolds.

ARYLSULPHONATES OF SPIROPYRAZOLINES AND O-TOSILATE-β-(BENZIMIDAZOL-1-YL)PROPIOAMIDOXYME AS THE PRODUCTS OF β-AMINOPROPIOAMIDOXIMES TOSYLATION

Pyrazolinium structures have practically valuable biological properties. Their methods of synthesis mainly consist in the reactions of cyclization of steroid compounds containing an enone fragment with a variety of hydrazines. We have previously obtained new spiropyrazolinium compounds by hydrolysis of 3-(β-heteroamino)ethyl-5-aryl-1,2,4-oxadiazoles and by arylsulfochlorination of β-aminopropioamidoximes. The aim of the work is to reveal the dependence of the structure of the final β-aminopropioamidoximes tosylation products from the structure of the starting amidoxime and strength of base. Methodology. The tosylation of β-aminopropioamidoximes was carried out in chloroform using diisopropylethylamine as a base. The synthesis was carried out at room temperature for 15–20 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the precipitate was filtered off, followed by evaporation of the filtrate and additional precipitation of the product; the combined precipitates were recrystallized from isopropanol. Results and discussion. The products of tosylation of β-aminopropioamidoximes were obtained in 45‒65% yields and identified using physicochemical and spectral [IR, NMR (1H and 13C)] characteristics, tosylation of β-aminopropioamidoximes (β-amino group: piperidin-1-yl, morpholine -1-yl, thiomorpholin-1-yl, 4-phenyl-piperazin-1-yl) proceeds with the formation of spirocyclic compounds ‒ arylsulfonates of 2-amino-1,5-diazaspiro [4.5]-dec-1-ene-5-ammonium; tosylation of β-(benzimidazol-1-yl)propioamidoxime gives the product on the oxygen atom of the amidoxime group.

Strategies and methodologies for the construction of spiro-fused γ-lactams: an update

Spiro-γ-lactams (spiropyrrolinin-2-ones) are a class of spirocyclic compounds that are present in a wide range of synthetic bioactive and naturally occurring molecules. The increasing attention to spirocyclic lactams in drug...

Oxa-spirocycles: synthesis, properties and applications

A general approach to a new generation of spirocyclic molecules - oxa-spirocycles - was developed. The key synthetic step was iodocyclization. More than 150 oxa-spirocyclic compounds were prepared. Incorporation of...