Cycloaddition Of Ylides Research Articles

Synthesis of Bioactive Fluoropyrrolidines through 1,3-Dipolar Cycloadditions of Azomethine Ylides

Synthesis of Bioactive Fluoropyrrolidines through 1,3-Dipolar Cycloadditions of Azomethine Ylides

Catalytic enantioselective intramolecular 1,3-dipolar cycloaddition of azomethine ylides with fluorinated dipolarophiles.

An enantioselective synthesis of polycyclic fluorinated pyrrolidines has been achieved by Cu-catalyzed intramolecular 1,3-dipolar cycloaddition of azomethine ylides with fluorinated dipolarophiles. The method displays a wide scope and afforded the desired cycloadducts in high yields with up to 99% ee. These results demonstrate that fluoroalkyl substituents are excellent activating groups in this transformation.

Asymmetric 1,3-dipolar cycloaddition of 4-amino pyrazolone-based azomethine ylides: a straightforward approach to spiropyrazolones

An asymmetric [3 + 2] cycloaddition of 4-amino pyrazolone-derived azomethine ylides with α,β-enones has been established for the synthesis of 4-spiropyrazolone derivatives with four contiguous stereocenters.

Синтез полизамещенных спиропирролидинов с использованием 2-ацетилфурана, 2-ацетилтиофена и 2-ацетилпиррола

A series of novel spirooxindoles have been synthesized through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the decarboxylative condensation of isatin and sarcosine with the dipolarophile 3-phenyl-1-(heteroaryl -2-yl)prop-2-en-1- one, synthesized by the Knoevenagel reaction using 2-acetylfuran, 2-acetylpyrrole, 2-acetylthiophene and substituted benzaldehydes. These compounds are used for the first time as dipolarophiles. This method has the advantages of mild reaction conditions, high atom economy, excellent yields, and high regio- and stereo-selectivity. The reaction was carried out by mixing equimolar amounts of enone and isatin, as well as a slight excess of sarcosine in isopropyl alcohol when heated to 60–70°C. Among the enones with various heterocyclic substituents, it is most convenient to use compounds containing a pyrrole fragment as dipolarophiles, since the products are obtained in a short amount of time in good yields. The use of enones obtained from 2-acetylthiophene leads to an increase in the reaction time, and from 2-acetylfuran - to a significant resinification of the reaction mixture. The structures of the compounds obtained were proved using a combination of 1H, 13C NMR spectroscopy data, as well as two-dimensional NMR experiments of heteronuclear correlation, HSQC and HMBC. Based on the data obtained, a mechanism for the formation of products has been proposed.

An easy access to highly substituted trispiroheterocycles – Synthesis of novel pyrazolo-1,4-dioxa-spiro[4,5]decane grafted spiro-oxindolopyrrolidines via a sequential multicomponent reaction

A facile one-pot sequential four-component synthesis of highly substituted trispiro heterocyclic system involving [3 + 2]-cycloaddition of azomethine ylides as the key step is described. The protocol provides a mild reaction condition, high yield of the products, high regioselectivity, and operational simplicity to assemble complex structural entity in a single operation. The structure of the product was confirmed by spectroscopic techniques, elemental and high-resolution mass spectrum analysis.

Stereoselective synthesis of PEGylated azoles via 1,3-dipolar cycloaddition

Abstract Diastereoselective synthesis of PEGylated imidazolidines, oxazolidines, thiazolidines, pyrrolo[3,4-c]pyrroles and fulleropyrrolidines in high yields is reported. The 1,3-dipolar cycloaddition of azomethine ylides generated via thermal ring-opening of PEGylated aziridines to ketenimines, ketenes, thioketones, maleimides, DMAD and fullerene C60 was found to proceed under different conditions. The use of C O, C N and C S dipolarophiles requires more harsh reaction conditions, compared with C C and C C dipolarophiles, to suppress the side reaction of aziridine “dimerization”. The stereocontrol of the product configuration is achieved through stereospecificity of two consecutive concerted reactions: electrocyclic aziridine ring opening followed by 1,3-dipolar cycloaddition of the resulting azomethine ylide: only trans-adducts are formed from cis-aziridines, whereas trans-aziridines give exclusively cis-adducts. The structure and molecular-mass distribution of the resulting PEGylated heterocycles are exhaustively characterized by 1H, 13C NMR, IR and HRMS.

A Pregnane Steroid as the Chiral Auxiliary in 1,3‐Dipolar Azomethine Ylide's Cycloaddition: Asymmetric Synthesis and Anticancer Activity of Novel Hybrid Compounds

AbstractHybrid chiral molecules containing frameworks of a pregnane steroid and 5‐arylpyrrolidine‐2,4‐dicarboxylate have been synthesized for the first time in a diastereomerically pure form. Chiral pregnane‐based acrylate induced stereoselective formation of all‐cis trisubstituted pyrrolidine moiety under cycloaddition with stabilized N‐metalated azomethine ylides. β‐Dipeptidic fragment was built up at C‐3 pregnane position using consequent acryloylation and stereoselective cycloaddition with stabilized N‐metalated azomethine ylide. All novel hybrid molecules demonstrated micromolar cytotoxic activity against human cervical epithelioid cancer HeLa cell culture in native and estradiol‐stimulated forms and breast carcinoma MCF‐7 cell culture. The most of hybrid compounds are less toxic towards human skin fibroblasts HSF as compared with studied hormonal tumor cells.

A facile atom – economical synthesis of highly substituted pyrazolo-N-methyl-piperidine grafted spiro-indenoquinoxaline pyrrolidine heterocycles via a sequential multicomponent reaction

An expedient one-pot sequential five component synthesis of highly substituted pyrazolo-N-methyl-piperidine grafted spiro-indenoquinoxaline pyrrolidine heterocycles involving [3 + 2]-cycloaddition of azomethine ylides as the key step is described. The protocol provides a mild reaction condition, high yield of the products, high regioselectivity and operational simplicity to assemble complex structural entity in a single operation. The structure of the product was confirmed by spectroscopic techniques and elemental analysis.

A facile synthesis of novel polycyclic spiropyrrolidine oxindoles incorporating the 1,3-dipolar cycloaddition of azomethine ylides

This study describes the synthesis of novel polycyclic spiropyrrolidine oxindoles through the 1,3-dipolar cycloaddition of azomethine ylides generated in situ with 3-(arylmethylene)-indolin-2-ones. Effect of substituents of azomethine ylides and various dipolarophiles on reactivity, as well as on the products regio- and stereoselectivity was investigated.

Synthesis and cytotoxicity of oxindoles dispiro derivatives with thiohydantoin and adamantane fragments

An effective and highly regio- and diastereoselective one-pot synthesis of two types of dispiro heterocyclic systems (2-thioxodispiro[imidazolidine-4,3′-pyrrolidine-2′,3″-indoline]-2″,5-diones and 2-thioxodispiro[imidazolidine-4,3′-pyrrolidine-4′,3″-indoline]-2″,5-diones) comprising pyrrolidinyl-oxindole, thiohydantoin and adamantane moieties has been developed based on a 1,3-dipolar cycloaddition of azomethine ylides, generated from isatin and sarcosine or formaldehyde and sarcosine, to adamantane-containing electron-deficient alkenes. Several molecules have demonstrated a considerable cytotoxicity against A549, HEK293T, MCF7 and VA13 cancer cell lines. The possible mechanism of anticancer activity of the synthesized compounds based on literature data may be the inhibition of p53/MDM2 interaction; however, we did not observe significant p53 activation using a reporter construction in A549 cell line in the relevant concentration range.

Synthesis of ferrocene-based polysubstituted pyrrolidines

Ferrocene-based polysubstituted pyrrolidines can be synthesized efficiently via 1,3-dipolar cycloaddition of azomethine ylides generated from α-amino acid ester and ferrocenecarboxaldehyde with N-substituted maleimide at 125°C in MeCN. The structures of the products were confirmed by 1H, 13C NMR, and HRMS data.

Asymmetric synthesis of polycyclic 3-fluoroalkylproline derivatives by intramolecular azomethine ylide cycloaddition

The asymmetric intramolecular dipolar cycloaddition of azomethine ylides was developed for fluorinated dipolarophiles, being the RF group crucial for selectivity.

Pyrrole ring closure reactions in the synthesis of isoindoles (microreview)

The microreview describes recent advances in the synthesis of isoindole derivatives via pyrrole ring closure reactions. We report the latest selected examples (2012–2018) on the synthesis of isoindoles: multicomponent reactions, [3+2] cycloaddition of azomethine ylides and munchnones, and transition metal-catalyzed C–H activation reactions.

A Chiral Secondary Amine–Amidophosphane Precatalyst for Silver-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition Reactions

A class of multifunctional amidophosphanes derived from chiral 1,2-diphenylethylenediamines and natural α-amino acids has been developed. Among these, in combination with silver(I) salts, a chiral secondary amine–amidophosphane precatalyst has been demonstrated as being a highly efficient multifunctional precatalyst in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides, including a series of heterocyclic, aliphatic, and 2-substituted azomethine ylides, and aromatic α,β-unsaturated aldehyde derived imino esters with different electron-deficient alkenes, as well as the three-component reaction of α-imino esters generated in situ by using N,N′-diisopropylcarbodiimide as dehydrating agent. Under optimal conditions, highly functionalized endo-adducts were obtained in high to excellent yields (up to 99% yield) and enantioselectivities (up to >99.9% ee).

A facile regio- and stereoselective synthesis of novel spiro[indolin-3,2′-pyrrolidin]-2-one’s via 1,3-dipolar cycloaddition of azomethine ylides

ABSTRACTA facile regio and stereoselective synthesis of novel spiro[indolin-3,2′-pyrrolidin]-2-one’s have been accomplished through 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the reaction of isatin and benzyl amine with quinoline bearing dipolarophiles in good yields. The synthesized compounds were well characterized through different spectroscopic techniques, such as single crystal XRD, FTIR, NMR, and mass spectral analysis.

Cycloaddition of Azomethine Ylides with Benzo[b]thiophene Sulfones

Cycloaddition of Azomethine Ylides with Benzo[b]thiophene Sulfones

Recent progress in insertion and cyclopropanation reactions of metal carbenoids from α-diazocarbonyl compounds

Metal–carbenoids from α-diazocarbonyl compounds are well-known reactive intermediates with a long history of useful applications in synthetic organic chemistry. The carbenoids, generated in situ from the catalytic decomposition of α-diazocarbonyls, react by different pathways such as insertions, cyclopropane formation, and cycloadditions of ylides, etc. in inter- and intramolecular versions of the reactions. These reactions have been employed in the architecture of several complex molecules of natural origin. The present review paper discusses the recent progress in catalytic insertion (X–H: X = C, N, O, S, Si, and B), and cyclopropane-forming reactions of α-diazocarbonyl compounds with a focus on regio-, diastereo-, and enantioselective reactions.

ChemInform Abstract: Enantioselective Dearomative [3 + 2] Cycloadditions of Indoles with Azomethine Ylides Derived from Alanine Imino Esters.

Catalytic, enantioselective [3 + 2] cycloadditions of azomethine ylides derived from alanine imino esters with 3-nitroindoles are reported. The dearomative cycloaddition reactions occur in the presence of a catalyst generated in situ from Cu(OTf)2 and (R)-Difluorphos to form exo′-pyrroloindoline cycloadducts and establish four contiguous stereogenic centers, two of which are fully substituted. The exo′-pyrroloindoline products are formed in moderate-to-good yields (39–85%) with high diastereoselectivities (up to 98 : 1 : 1 dr) and enantioselectivities (up to 96% ee).

1,3-Dipolar cycloadditions of nonstabilized azomethine ylides to planar chalcones via regio- and stereoselective route: A three-component strategy

ABSTRACTSimple and efficient strategies toward the synthesis of trisubstituted pyrrolizidines and disubstituted oxazolidine systems by 1,3-dipolar cycloaddition reactions using arylaldehydes and α-amino acids have been developed, followed by a one-pot, three-component strategy. Electron-deficient dipolarophiles, chalcones, were reacted with nonstabilized azomethine ylides derived from arylaldehyde and L-proline in dry dimethyl formamide, leading to substituted pyrrolizidines. The route to substituted oxazolidines involved cycloaddition to the C˭O bond of a second molecule of the aldehyde. The structures and stereochemistry of the cycloadducts were established by infrared (IR), NMR spectroscopy, and single-crystal x-ray crystallographic analyses. Condensed Fukui functions and local electrophilicity indices have been computed to characterize the reactive sites and predict the preferred interactions of azomethine ylides to planar chalcones. The softness-matching indices have been evaluated to determine the regioselectivity of the cycloaddition reactions. The theoretical predictions were found to be in complete agreement with the experimental results, implying that the density functional theory (DFT)-based reactivity indices correctly predict the regioselectivities of 1,3-dipolar cycloadditions of azomethine ylides to planar chalcones. The frontier molecular orbital (FMO) energies, electronic chemical potentials, chemical hardness, chemical softness, and global electrophilicity indices of azomethine ylides have been calculated at the DFT/B3LYP/6-31 + G (d, p) level of theory.

Asymmetric [3+2] Cycloaddition of Azomethine Ylides with Acyclic 1,3-Dienes

Asymmetric [3+2] Cycloaddition of Azomethine Ylides with Acyclic 1,3-Dienes