Electron-deficient Substrates Research Articles

Conjugate addition to diethyl azodicarboxylate under organic-perfluorinated biphasic homogeneous catalysis by nickel(II) species

The nickel(II) complex of the Schiff base of salicylaldehyde and 4-perfluorodecylaniline catalyzes the conjugate addition of β-diketones to electron-deficient substrates. Electrophilic amination with azodicarboxylate affords quaternary centers. The catalyst is recovered in solution and reutilized. Isolation of reaction products is very simple and does not require chromatography.

Molecular Tweezers as Synthetic Receptors: Molecular Recognition of Electron-Deficient Aromatic Substrates by Chemically Bonded Stationary Phases

The synthesis and chromatographic properties of novel chemically-bonded stationary phases CBSP-1 and CBSP-2, containing substituted molecular tweezers with benzene and naphthalene spacer-units, are described. These phases selectively retain electron-deficient aromatic and quinoid analytes of appropriate size and topography, such as 1,4-dinitrobenzene, 1,2-, 1,3-, and 1,4-dicyanobenzenes, and 7,7,8,8-tetracyano-p-quinodimethane (TCNQ), in HPLC studies. The good qualitative correlation between the capacity factors k′ derived from the HPLC retention times and the association constants Ka obtained from binding studies in solution using molecular tweezers 1 and 2 as receptors, indicates that the mechanism of retention involves selective complexation by the molecular tweezers on the silica surface. As expected from the solution experiments, higher capacity factors and selectivities were obtained with CBSP-2 than with CBSP-1 because of a better structural fit of the naphthalene-spaced receptor with the aromatic analytes. Capacity factors, k′, and enthalpies of retention, ΔHR, were measured for four different aromatic analytes in 15 solvents. Chromatographic separation factors, α, were determined for seven structurally-related nitroaromatic compounds. The results of these measurements allow for the conclusion that the electrostatic nature and steric complementarity of the receptors and analytes is most important in determining selectivities.

Molecular Tweezers as Synthetic Receptors: Molecular Recognition of Electron-Deficient Aromatic Substrates by Chemically Bonded Stationary Phases

The synthesis and chromatographic properties of novel chemically-bonded stationary phases CBSP-1 and CBSP-2, containing substituted molecular tweezers with benzene and naphthalene spacer-units, are described. These phases selectively retain electron-deficient aromatic and quinoid analytes of appropriate size and topography, such as 1,4-dinitrobenzene, 1,2-, 1,3-, and 1,4-dicyanobenzenes, and 7,7,8,8-tetracyano-p-quinodimethane (TCNQ), in HPLC studies. The good qualitative correlation between the capacity factors k′ derived from the HPLC retention times and the association constants Ka obtained from binding studies in solution using molecular tweezers 1 and 2 as receptors, indicates that the mechanism of retention involves selective complexation by the molecular tweezers on the silica surface. As expected from the solution experiments, higher capacity factors and selectivities were obtained with CBSP-2 than with CBSP-1 because of a better structural fit of the naphthalene-spaced receptor with the aromatic analytes. Capacity factors, k′, and enthalpies of retention, ΔHR, were measured for four different aromatic analytes in 15 solvents. Chromatographic separation factors, α, were determined for seven structurally-related nitroaromatic compounds. The results of these measurements allow for the conclusion that the electrostatic nature and steric complementarity of the receptors and analytes is most important in determining selectivities.

Substrate-selective mechanisms in biocatalysis demonstrated with a versatile and efficient aldolase antibody

A structure-activity relationship study with a series of aldol substrates shows that the mechanism of the antibody 38C2-catalyzed retrograde aldol reaction depends on the nature of the substrate With electron-deficient substrates an early deprotonation precedes the CC bond cleavage while with electron-rich substrates the catalytic mechanism involves an initial CC bond cleavage leading to a positively charged intermediate.

Carbon versus oxygen nucleophilic selectivity in the reaction of the aryloxide ions, 2,6- and 3,5-di-tert-butylphenoxide, with the 2-[(nitro)\dn6 xaryl]-4,6-dinitrobenzotriazole 1-oxide series of super-electrophiles. Stereoelectronic factors on C-7 Meisenheimer complex formation versus C-1' SNAr displacement

The 2-[(nitro)xaryl]-4,6-dinitrobenzotriazole 1-oxides (1, Pi-DNBT (x = 3); 2, DNP-DNBT (x = 2); 3, NP-DNBT (x = 1)) are electron-deficient nitro-substituted heteroaromatic substrates that possess two sites for nucleophilic attachment: C-7 and C-1'. Generally, attack at the super-electrophilic C-7 site yields spectroscopically observable anionic sigma -bonded adducts, whereas attack at C-1' leads to displacement products in an overall process of nucleophilic aromatic substitution (SNAr). To gain an understanding of the factors affecting C-1' versus C-7 attack by potentially ambident aryloxide (C- and O-)nucleophiles, we have monitored the reactions of 1-3 with 2,6-di-tert-butylphenoxide (2,6-ArO-) and 3,5-di-tert-butylphenoxide (3,5-ArO-) using 400 MHz 1H NMR spectroscopy (deuterated dimethyl sulfoxide solvent at ambient temperature). The results indicate that 2,6-ArO- acts only as a C-nucleophile with O-attack precluded, presumably by the sterically demanding tert-butyl groups flanking the O-nucleophilic centre. Although 2,6-ArO- reacts preferentially at C-7 of 1-3, the biphenyl derivative that arises from C-1' attack is also observed with 1, the first time that C-nucleophilic attack has been seen at this electrophilic site. In contrast, 3,5-ArO- acts only as an O-nucleophile, also as a consequence of the steric hindrance to the C-4 position; this aryloxide reacts entirely at C-1' of Pi-DNBT but also exclusively at C-7 of 3. However, with DNP-DNBT, 2, both the C-7 O-adduct and C-1' displacement products are noted; attack at C-1' is dominant. The selectivity (C-7 versus C-1') found in these reactions is discussed with emphasis given to stereoelectronic factors that may stabilize the putative C-1' O-adducts.Key words: aryloxides, super-electrophiles, Meisenheimer complexes, 2-[(nitro)xaryl]-4,6-dinitrobenzotriazole 1-oxides.

Palladium-Catalyzed Amination of Aryl Triflates

The conversion of aryl triflates to the corresponding aniline derivatives was accomplished in moderate to good yield using a catalyst consisting of the combination of palladium acetate (2 mol %) and either BINAP or Tol-BINAP. In contrast to the corresponding palladium-catalyzed amination of aryl bromides and iodides, electronically neutral aryl triflates gave higher yields of arylamines than did electron deficient aryl triflates, presumably due to the increased rate of base-promoted triflate cleavage in electron deficient substrates.

Enhanced nucleophilic character of the 1-adamantyl radical in chlorine atom abstraction and in addition to electron-poor alkenes and to protonated heteroaromatic bases. Absolute rate constants and relationship with the Gif reaction

The absolute rate constants for reactions of the 1-adamantyl radical with electron-deficient substrates have been measured by competition kinetics. Addition to electron-poor alkenes or to protonated heteroaromatic bases, as well as chlorine abstraction from CCl4 and CHCl3, are two to three orders of magnitude faster than the corresponding reactions of the tert-butyl radical. This behaviour is ascribed to the enhanced nucleophilic character of the 1-adamantyl radical compared to generic tertiary alkyl radicals; it is related to the particular stability of the 1-adamantyl cation and to the low oxidation potential of adamantane. These results contribute to the understanding of the Gif reaction mechanism; in this debate, adamantane oxidation was one of the most controversial aspects because the 1-adamantyl radical is trapped by pyridinium ions, while the 2-adamantyl radical is not. This behaviour is explained by the large difference in the reactivity of the two isomeric adamantyl radicals towards protonated pyridine.

Photoelectron transfer catalysed reactions of amines with α,β-unsaturated esters and acrylonitrile using different sensitizers

A variety of sensitizers were screened for their ability to photocatalyse efficiently the carbon-carbon bond forming reactions between primary and secondary amines with electron-deficient olefinic substrates, such as α,β-unsaturated and acrylonitrile. The reactions with α,β-unsaturated esters led to the formation of lactams as the major products. Dicyanoanthracene and acridone were found to be inefficient, while anthraquinone, benzophenone, anthrone and xanthone photocatalyse these reactions with moderate efficiency. The anthraquinone-2-sodium sulphonate catalysed addition of tertiary amines to α,β-unsaturated esters in aqueous medium also yielded lactams as the major products. Reasonable mechanisms have been suggested for the formation of the different products.

Selective Epoxidation of Olefins by Perfluoro-cis-2,3-dialkyloxaziridines(1).

Alkyl-substituted olefins are epoxidized by perfluoro-cis-2,3-dialkyloxaziridines under particularly mild conditions. Electron deficient substrates (e.g. alpha,beta-enones) can also be epoxidized, and the more electron poor the double bond is, the more severe the reactions conditions become. The epoxidation is chemoselective (secondary alcohols and their ethers do not interfere), site selective (the monoepoxide of a diene can be obtained), and stereoselective (cis-alkenes afford cis-epoxides). Various complex and polyfunctional substrates of natural origin (monoterpenes, sesquiterpenes, steroids) have been transformed effectively.

Solvent effects in molecular recognition

Abstract

Benzvalene—Properties and Synthetic Potential

AbstractToday, thanks to the versatile synthesis developed by Katz et al., benzvalene is not only the most extensively studied valence isomer of benezene but also one of the most easily synthesized bicyclo[1.1.0]butane derivatives. The double bond in this highly strained hydrocarbon is particulary reactive owing to interactions between the σ system and the double bond. Benzvalene is one of the most reactive olefins toward electron deficient substrates. Furthermore, the compound is bifunctional, since after addition to the π system the ring strain of the σ system provides the driving force for rearrangement or further addition reactions. This paper summarizes the spectroscopic properties and the reactivity of benzvalene. In order to demonstrate the importance of benzvalene and its derivatives as building blocks in organic synthesis the chemistry of compounds arising from benzvalene is also discussed. The article concludes with a summary of substituted benzvalenes.

The Nucleophilic Reaction of Electron-deficient Pyridone Derivatives. I. The Ring Transformation of 1-Substituted 3,5-Dinitro-2-pyridones with Sodio β-Keto Esters

Abstract A novel ring transformation is found in a series of reactions of 1-substituted 3,5-dinitro-2-pyridones, electron-deficient substrates, with monosodium salts of β-keto esters. A variety of 1-substituted 3,5-dinitro-2-pyridones are treated with diethyl sodio-3-oxopentanedioate and ethyl sodioacetoacetate to give, in addition to N-substituted nitroacetamides (3), 2,6-bis(ethoxycarbonyl)-4-nitrophenol (2), and 2-ethoxycarbonyl-4-nitrophenol (4) respectively. The bicyclic intermediates, 2-azabicyclo[3.3.1]nona-3,7-dienes, can be isolated on the reaction of 3,5-dinitro-1-methyl-2-pyridone at room temperature. The phenol derivatives (2 and 4) may consist of the reagent and a C4–C5–C6 moiety of the parent pyridone, while N-substituted nitroacetamides, 3, may result from the other fragment, N–C2–C3, of the pyridone. A probable course of the reaction, involving the step-by-step nucleophilic attack of the ambident nucleophiles, sodio β-keto esters, at the ambident electrophilic centers of 2-pyridones to form bicyclic intermediate, is proposed.

Metalloidalmethyl substituent effects by 13C and 19F NMR : electron release in the neutral ground state.

13C and 19F chemical shift studies of a series of CH 2M(CH 3) 3 and CH 2M(C 6H 5) 3 (M  Si, Ge, Sn, Pb) - substituted aryl derivatives (phenyl; 1-naphthyl; 2-naphthyl) have established unambiguously that the order of hyperconjugative electron release in the neutral ground state is Pb>Sn>Ge>Si. This order is clearly at variance with the commonly accepted order(Pb>Sn>Ge>Si) based on studies of electron deficient substrates. The phenomenon is discussed in terms of current theories on σ-π interactions. In addition, substituent parameters (σ I and σ R o) for the PB(CH 3) 3 group have been derived utilizing new data from the fluorophenyl tag. These new constants are compared with those previously reported.