Synthesis of Dispirocyclopentyl‐3,3′‐bisoxindoles via Domino Cycloaddition Reactions of 4‐Dimethylaminopyridinium Bromides with 3‐Phenacylideneoxindoles

The base mediated cycloaddition reactions of 4‐dimethylamino‐1‐phenacylpyridinium bromides with two molecular 3‐phenacylideneoxindoles in methylene dichloride afforded functionalized dispirocyclopentyl‐3,3′‐bisoxindoles in good yields and with high diastereoselectivity. The similar cycloaddition reactions of 1‐(N,N‐dialkylcarbamoylmethyl) and 1‐cyanomethyl 4‐dimethylamino‐pyridinium bromide in refluxing ethanol in the presence of triethylamine also resulted in dispirocyclopentyl‐3,3′‐bisoxindoles with high diastereoselectivity. The stereochemistry of dispirocyclopentyl‐3,3′‐bisoxindoles was elucidated on the basis of ¹H NMR data and single crystal structures.     

trans-4-Hydroxy-l-proline: a novel starting material for N-alkylpyrroles synthesis

The reaction of aldehydes with trans-4-hydroxy-l-proline was studied for the first time, resulting in the formation of N-alkylpyrroles in good to excellent yields, via decarboxylation followed by redox isomerization under neutral conditions. The neutral conditions allow access to efficient synthesis of N-alkyl pyrroles with high functional group tolerance.     

Structural, theoretical and multinuclear NMR study of mercury(II) complexes with a new ambidentate phosphorus ylide

The reaction of the new ambidentate ylide, Ph₃PCHCOCH₂COOC₂H₅ (EAPPY), with HgX₂ (X = Cl, Br and I) in equimolar ratios using methanol as the solvent leads to binuclear complexes of the type [EAPPY·HgX₂]₂ (X = Cl (1), Br (2) and I (3)). Single crystal X-ray analysis reveals the presence of a centrosymmetric dimeric structure containing the ylide and HgX₂ (X = Br or I)_. The IR and NMR data of the product [(EAPPY)·HgCl₂]₂ (1), formed by the reaction of mercury(II) chloride with the same ylide, are similar to those of 2 and 3. Analytical data indicate a 1:1 stoichiometry between the ylide and Hg(II) halide in each of the three products. Theoretical studies indicate that the nature of the R group in ylides of the type Ph₃PCHCOR has a weak effect on the Hg-C(ylide) bond length in binuclear Hg₂L₂I₄ complexes.     

Enantioselective Protonation of Cyclic Carbonyl Ylides by Chiral Lewis Acid Assisted Alcohols

Chiral Lewis acid-catalyzed asymmetric alcohol addition reactions to cyclic carbonyl ylides generated from N-(α-diazocarbonyl)-2-oxazolidinones featuring a dual catalytic system are reported. Construction of a chiral quaternary heteroatom-substituted carbon center was accomplished in which the unique heterobicycles were obtained in good yields with high stereoselection. The alcohol adducts were successfully converted to optically active oxazolidine-2,4-diones by hydrolysis. Mechanistic studies by DFT calculations revealed that alcohols could be activated by Lewis acids, enabling enantioselective protonation of the carbonyl ylides.     

Difluorocarbene-Induced Ring-Opening Difluoromethylation-Halogenation of Cyclic (Thio)Ethers with TMSCF2X (X=Br,Cl)**

The ring-opening difluoromethylation-halogenation of cyclic (thio)ethers is reported through a simple strategy relying on carbon-chalcogen bond activation with difluorocarbene. The reaction proceeds through in situ protonation of the previously little-known difluoromethylene oxonium or sulfonium ylide intermediate followed by ring-opening with halide ion to afford halogenated acyclic difluoromethyl (thio)ethers that can then be employed for further elaboration. TMSCF₂X (X=Br, Cl) are unique reagents to achieve this synthetic purpose, which serve as both the difluorocarbene source and the halide ion source.     

A Molecular Electron Density Theory Study of the [3+2] Cycloaddition Reaction of an Azomethine Ylide with an Electrophilic Ethylene Linked to Triazole and Ferrocene Units

The [3+2] cycloaddition (32CA) reaction of an azomethine ylide (AY) with an electrophilic ethylene linked to triazole and ferrocene units has been studied within the Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311G(d,p) level. The topology of the electron localization function (ELF) of this AY allows classifying it as a pseudo(mono)radical species characterized by the presence of two monosynaptic basins, integrating a total of 0.76 e, at the C1 carbon. While the ferrocene ethylene has a strong electrophilic character, the AY is a supernucleophile, suggesting that the corresponding 32CA reaction has a high polar character and a low activation energy. The most favorable ortho/endo reaction path presents an activation enthalpy of 8.7 kcal·mol⁻¹, with the 32CA reaction being exergonic by −42.1 kcal·mol⁻¹. This reaction presents a total endo stereoselectivity and a total ortho regioselectivity. Analysis of the global electron density transfer (GEDT) at the most favorable TS-on (0.23 e) accounts for the high polar character of this 32CA reaction, classified as forward electron density flux (FEDF). The formation of two intermolecular hydrogen bonds between the two interacting frameworks at the most favorable TS-on accounts for the unexpected ortho regioselectivity experimentally observed.     

Manganese Dioxide is an Efficient Catalyst for the Stereoselective Conversion of Dialkyl 2-(Imido-N-yl)-3-(triphenylphosphoranylidene)butanedioates to Electron-Poor (Z)-N-vinylimides in Solvent-Free Conditions

Manganese dioxide was found to catalyze stereoselective conversion of dialkyl 2-(imido-N-yl)-3-(triphenylphosphoranylidene)butanedioates to electron-poor (Z)-N-vinylimides in solvent-free conditions at 95°C in high coversions.     

1,3-Dipolar cycloadditions with azomethine ylide species generated from aminocyclopropanes

Two types of bicyclic N-cyclopropyl glycine ester derivatives have been prepared and put under scrutiny as possible precursors of azomethine ylides. The results demonstrate that they can indeed participate in 1,3-dipolar cycloaddition reactions with dipolarophiles, as illustrated in the cases of phenyl vinyl sulfone, N-phenylmaleimide, diethyl fumarate and diethyl maleate. The relative configurations of the major diastereoisomers produced are consistent with the predicted generation of azomethine ylide species, reacting in concerted cycloaddition processes. This unprecedented way of generating such 1,3-dipoles provides access to functionalised pyrrolizidine and pyrrolidine derivatives, that would be difficult to make directly by more classic methods. It was also found that using phenyl vinyl sulfone or N-phenylmaleimide as the dipolarophile reactant, a domino nucleophilic conjugate addition/1,3-dipolar cycloaddition process may operate competitively.     

Mechanistic approaches to asymmetric synthesis of aziridines from guanidinium ylides and aryl aldehydes

To approach more realistic mechanisms for asymmetric aziridine synthesis from guanidinium ylides and aryl aldehydes, reactions were systematically carried out by using a variety of p-substituted benzaldehydes under modified conditions. Two kinds of reaction mechanisms controlled by the nature of the p-substituents of aryl aldehydes is proposed for the two-steps aziridine synthesis composed of a C-C bond formation by nucleophilic addition of guanidinium ylides to aryl aldehydes (step 1) and the fragmentation of intermediate adducts to aziridine products by intramolecular nucleophilic substitution (step 2). A S_Ni-like mechanism via cationic-like transition state is proposed for step 2 in the asymmetric synthesis using EDG-substituted benzaldehydes, whereas with EWG-substituted benzaldehydes, a S_N2-like mechanism is proposed. Hammett analysis, based on the diastereomeric ratio in the aziridine products, is consistent with the proposed rate-determining steps in these two mechanisms. A second Hammett analysis, based on the enantiomeric ratio of the aziridine products, clearly reveals the difference in the susceptibilities to the electronic substituents effect between step 1 and step 2.     

Electronic structure and conformational flexibility of 1,4-dihydroazines and their 4-ylide derivatives

The conformational flexibility of 1,4-dihydropyridine, 1,4-dihydropyrimidine, 1,4-dihydropyridazine, 1,4-dihydro-1,3,5-triazine, and their 4-oxo, imino, and methylene derivatives was studied by the semiempirical quantum-chemical AM1 method. It was demonstrated that the replacement of the methylene group in the dihydroazine ring by the exocyclic double bond results only in an increase in the rigidity of the heterocycle rather than leading to a loss of its conformational flexibility. It was suggested that nonplanar conformations of rings in ylide derivatives are stabilized by the nonaromatic cyclic -system. Introduction of the exocyclic double bond does not cause a substantial change in the -electronic structure of the heterocycle. The aromaticity indicesI ₆ andI ₆() were calculated. The correlation between these indices and a change in the energy upon bending of the heterocycle was established.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No 8 pp 1938–1941, August, 1996.