Captodative Research Articles

Role of Polar and Enthalpic Effects in the Addition of Methyl Radical to Substituted Alkenes: A Density Functional Study Including Solvent Effects

The addition of methyl radical to mono- and disubstituted alkenes has been studied by a hybrid Hartree−Fock/density functional method taking into account solvent effects by the polarizable continuum model. The reliability of the electronic approach has been verified by comparison with refined post-Hartree−Fock computations and with experimental data. Environmental effects do not alter the trends of in vacuo computations due to the low dielectric constant of the solvent and to the lack of significant charge separation effects. Use of substrates characterized by captodative effects and comparison with a genuine nucleophilic radical (CH2OH) allow one to unequivocally conclude that CH3 does not behave as a nucleophile. As a consequence polar effects are negligible and activation barriers are governed by the stability of the forming radical. These trends are confirmed by electron population analysis and evaluation of charge-transfer energies.

Radical reactions leading to substituted pyroglutamates

The Bu 3 SnH mediated cyclisation of a serine-derived dehydroalanine was shown to provide an efficient approach to a protected 4-phenylpyroglutamate which was elaborated to 4-phenylglutamic acid in good yield. Cyclisation reactions of this type were shown to proceed via an intermediate captodative radical which could be trapped intermolecularly using an alkene e.g. styrene or methyl methacrylate. This method has potential for the synthesis of various 4- and/or 2-substituted glutamic acids. Radical cyclisation of a dehydroalanine can be used to prepare 4-phenylglutamic acid. Reactions of this type proceed via captodative radicals ( 1 ) which can be trapped to afford 2-substituted pyroglutamates e.g. ( 2 ) and ( 3 ).

Are α-centered peptide radicals stabilized by a capto-dative effect?

The kinetics of the thermal C-C-cleavage reaction of the dimer of sarcosine anhydride 5 has been investigated between 295 and 333 °C in mesitylene. From the temperature dependence and from the release of strain on dissociation the cyclic α-peptide radical 6 was calculated to have a radical stabilization enthalpy (RSE) of −6.3 ± 1.3 kcal/mol thus indicating the absence of a synergistic capto-dative effect.

Oxidation of Oxazolines and Thiazolines to Oxazoles and Thiazoles. Application of the Kharasch-Sosnovsky Reaction.

Using a modification of the Kharasch-Sosnovsky reaction, the oxidation of oxazolines and thiazolines bearing a variety of 2-alkyl substituents (chiral and achiral) were smoothly oxidized to their corresponding oxazoles and thiazoles, respectively. The key feature involved in the successful implementation of this important oxidation was the use of a mixture of Cu(I) and Cu(II) salts to enhance the oxidation of the intermediate captodative radical, 24. The main limitation of this method was shown when the oxidation failed with oxazolines/thiazolines lacking the carboalkoxy group at C-4.

Ab initio study of conjugative and negative hyperconjugative interactions in disubstituted radicals

Electronic interactions in disubstituted radicals CHXY (X, Y is F, OH or NH 2) have been probed by examining the energetics of numerous conformations at the UMP3/6-31G(d)//ROHF/4-31G level. Negative hyperconjugative interactions in these radicals are indicated to be comparable in magnitude to π conjugation. Most of these disubstituted radicals are predicted to adopt unsymmetrical geometries in order to benefit from both types of stabilizing interactions. These results have interesting implications for reactions involving carbohydrate radicals, for which the simple systems serve as models. Thus, the structures and energetics of the dihydroxymethyl radical have been used to explain the observed stereoselectivity of a few reactions involving sugar-based radicals. The non-additivities of substituent effects in the disubstituted radicals have been compared with the magnitude of the anomeric effect in the corresponding disubstituted methanes. The inter-substituent interactions in the radicals should not be overlooked when using these systems as reference species in estimating other non-additive effects, such as the captodative effect.

Design of unusual captodative methylene substrates: 1-Alkyl-4(3)-(azolylmethyl)pyridinium salts 1

The unprecedented spontaneous oxidation of a carbon atom linked to captor (acceptor) and donor non-classical functional groups of several examples of 1-alkyl-4(3)-(1 H-azolylmethyl) pyridinium salts 1 and 2 exemplifies a concomitant application of the arenoanalogy principle and the captodative effect in organic synthesis. A remarkably driving force by the nature of non-classical acceptor and donor heteroaromatic rings is observed upon the chemical behavior of the title compounds 1 and 2, modulating the susceptibility with which the methylene spacers oxidize to their oxomethyl counterparts 5 and 6. Access to dipolar 1-alkyl-3-pyridiniomethyl-3(5)-1,2,4-triazolate inner salts 4 was achieved.

The Photolytic Disproportionation of Dialkyl 2,2-Di(Phenylseleno)propanedioates

Abstract Dialkyl-2,2-di(phenylseleno)propanedioates undergo disproportionation to form tetralkyl 1,1,2,2-ethylene tetracarboxylates and diphenyl diselenide upon photolysis. Evidence for the intermediacy of a capto-dative radical intermediate in this process is described.

ChemInform Abstract: Photoreduction of α‐Ketoamides; Cyclization of Unsaturated Captodative Radicals.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Photoreduction of α-ketoamides; cyclization of unsaturated captodative radicals

When N-allyl α-ketoamides are irradiated in the presence of t-amines, a reductive photocyclization to hydroxypyrrolidones is observed. The reaction involves cyclization of an unsaturated captodative radical

Transition metal-catalyzed chlorine transfer cyclizations of carbon-centered glycine radicals; A novel synthetic route to cyclic α-amino acids

Copper(I)-catalyzed chlorine transfer radical cyclizations of several α-chloroglycine derivatives with a 3-alkenyl substituent at nitrogen are reported. These reactions proceed via 2-aza-5-alken-1-yl radicals as intermediates which bear electron-withdrawing carbonyl substituents at the radical center and at nitrogen. These radicals can be considered as relatively stable captodative radicals, which are easily generated in the presence of Cu(bpy)Cl, but are reactive enough for olefin cyclization. The main products usually arise from 5- exo cyclization and are structurally interesting analogues of proline. An X-ray crystal structure of one of the cyclization products is presented.

Theoretical Investigation of Some Evidences of the Captodative Effect

AbstractIn this paper, the stability and reactivity of some gem‐disubstituted closed‐shell and open‐shell systems are investigated using the unifying concept of thermodynamic stabilization energy. We deduce this quantity either from available experimental data or from enthalpies of formation obtained at various theoretical levels. The energies of open‐shell species, medium‐size closed‐shell systems and large diamagnetic compounds are respectively calculated at the CISD/6‐31 G(d,p), MP2 = FULL/6‐31 G(d,p) and HF/6‐31 G(d,p) levels.It is found that captodative (cd) substitution significantly stabilizes carbon‐centred radicals and ethylenic compounds but generally destabilizes methane derivatives. Didative (dd) substitution most often stabilizes both the methyl radicals and their parent molecules. Finally most cc‐substituted species are destabilized. On the whole, the cdCH2 compounds do actually have the smallest C‐H bond strengths due to the joint action of the captodative and stereoelectronic effects. For this reason, they deserve to be named proradical. Consequently hydrogen transfer reactions are strongly favoured by captodative substitution which explains the selectivity induced by this substitution in dehydrodimerization reactions. Radical additions to alkenes are facilitated by dicaptor and captodative substitutions while donor groups have a relatively small influence on the thermochemistry of these reactions. In the absence of steric effects, didative and captodative olefines could probably give rise to radical polymerization.

Radical additions of simple piperazine-25-diones

The polar character of a simple piperazine-2,5-dione was investigated under intermolecular radical addition conditions. The results indicate that captodative radical of this kind neither show extreme nucleophilic nor electrophilic tendencies.

Structures of <I>α</I>-Chloromethylsulfide Radical and its Captodative Effect

Structures of <I>α</I>-Chloromethylsulfide Radical and its Captodative Effect

Radicals containing both a phosphoranylidene and a ketone group: an electron paramagnetic resonance/electron nuclear double resonance study of their structure and ab initio investigations on the captodative effects

Single crystals of 2-(triphenylphosphoranylidene)succinic anhydride have been X-irradiated and studied by electron paramagnetic resonance/electron nuclear double resonance (EPR/ENDOR) spectroscopy after determination of their crystal structure. The trapped radical results from the departure of a hydrogen atom bound to a carbon located α to both a CP and a CO bond. The resulting hyperfine coupling tensors are compared with those obtained from ab initio calculations on H3PCH—ĊH—CHO (1) and are interpreted in terms of spin delocalization on the succinic anhydride ring. The radical stabilization energies have been calculated for H3PCH—ĊH—CHO and H2P—CH2—ĊH—CHO; they agree with the presence of a captodative effect. Owing to the charge separation caused by the contribution of the mesomeric phosphonium–enolate structure, this effect is more pronounced for the phosphoranylidene compound.

Evidence for dose rate effect in gamma-radiolysis—II. Methylmethoxyacetate in 2,3-dimethylbutane and in cyclohexane

Solutions of 2,3-dimethylbutane (DMB) and cyclohexane containing a captodative solute, methylmethoxyacetate (MMA), were irradiated (continuous wave). Alkane dimeric products were analysed by capillary gas chromatography. G-yields were estimated as a function of the concentration of the captodative solute. By reaction with alkyl radicals, the captodative solute gives the free radical stabilized by the captodative effect. Combination reaction of this radical with itself or with alkyl radicals gives solute or mixed dimer which were also analysed. A large intensity effect was noticed, as was seen in the solutions of n-hexane-MMA. Dose effect was definitely rejected.

Radical-transfer catalysis versus Lewis acid catalysis by the copper(I) chloride/2,2′-bipyridine complex: an illustration of the synthetic significance of captodative radical stabilization

The mechanism of the copper(I) chloride/2,2′-bipyridine catalysed π-cyclization of N-(chloromethyl)alk-3-enylcarbamates changes from a cationic process (leading to piperidines) into a radical-transfer process (leading to pyrrolidines) upon introduction of an ester substituent at the reactive carbon atom, owing to the captodative effect.

Reductive cyclization of carbon-centered glycine radicals; a novel synthetic route to cyclic α-amino acids

Reductive cyclizations (tributylin hydride, AIBN) of several α-(penthylthio)glycine derivatives with a 30alkenyl substituent at nitrogen are reported. These reactions proceed via 2-aza-5-alken-1-yl radicals as intermediates which bear electron-withdrawing carbonyl substituents at the radical center and at nitrogen. Such radicals can be considered as relatively stable captodative radicals, but are reactive enough for olefin cyclization. The main products usually arise from 5- exo cyclization and are structurally interesting analogues of proline. Varying amounts of pipecolic acid analogues via 6- endo cyclization are also obtained in some cases. A similar cyclization of an acetylene is successful, whereas a nitrile fails to cyclize.

The influence of gew-substitution on the stability of open-shell and closed-shell systems. The captodative and anomeric effects re-examined

In this paper we examine the influence of gem-substitution on the stability of carbon-centred radicals and their parent molecules, using the unifying concept of thermodynamic stabilization energy. We deduce this quantity either from available experimental data or from theoretical enthalpies of formation calculated at various theoretical levels. It is found that captodative substitution significantly stabilizes carbon-icentred radicals and generally destabilizes methane. Moreover, most captodative (cd) radicals studied in this work possess a sizable extra stabilization which demonstrates a synergetic effect of the captor and donor substituents at the radical centre. Didative (dd)-substituted methyl radicals and parent molecules are most often stabilized by a non-negligible anomeric effect. Finally most cc-substituted species are destabilized. On the whole, cdCH 2 compounds have systematically lower C-H bond strengths than ccCH 2 and ddCH 2 species due to the joint action of the captodative and the generalized anomeric effects. We have also shown that enthalpies of reactions can not be used to analyse the influence of substituents on the stability of chemical species. More particularly, the energy changes of the processes R . + CH 4 → RH + ·H 3 and those of group separation reactions are far from being equal to radical and anomeric stabilization energies, respectively.

New type of charge-transfer complex from an antiaromatic electron donor. Possible radical cation stabilization by the captodative effect

We report the synthesis and characterization of a novel electron donor for CT salts based on the 1,4-dihydropyrazine ring system, 4a,8a-diaza-2,6-dioxa-3,4,7,8-tetahydro-4,4,8,8-tetramethylanthracene-1,5-dione (DDTTA), and its oxidation to an exceptionally persistent, captodatively stabilized radical cation

Photochemistry of 1-alkoxy- and 1-(benzyloxy)-9,10-anthraquinones in methanol: a .delta.-hydrogen atom abstraction process that exhibits a captodative effect

The photochemistry of a variety of 1-alkoxy- and 1-(benzyloxy)-9,10-anthraquinones in methanol has been examined. In the absence of oxygen the primary photoproducts of these reactions are 9,10-anthrahydroquinones with MeOCH 2 O and ArCH(OMe)O groups at the 1-position, respectively. Quenching studiens established the multiplicity of the excited state to be triplet. Deuterium isotope effects, substituent effects, and solvent polarity studies support a mechanism in which a biradical intermediate is formed by an intramolecular δ-hydrogen atom transfer that occurs in one step but not a reaction pathway in which the hydrogen atom transfer is accomplished in two discrete steps via separate electron and proton transfers. Apparent rate constants for the disappearance of 1-(p-XPhCH 2 O)-2-methyl-9,10-anthraquinone (X=H, Cl, CH 3 , NO 2 , OCH 3 , CF 3 , and CN) were measured and found to vary by a factor of 3.4 from the largest (X=NO 2 ) to the smallest (X=OCH 3 ). Captodative interactions account for the small differences in these rate constants