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Addition of various organic O-centered radicals XO• {i.e. (alkoxycarbonyl)oxyl radicals, ROC(O)O•, [(alkoxycarbonyl)acyl]oxyl radicals, ROC(O)C(O)O•, (carbamoyl)oxyl radicals, R2NC(O)O•, alkoxyl radicals, RO•, and nitroxyl radicals, R2NO•} to alkynes initiates an oxidative radical cyclization cascade, which is terminated by release of a C- or N-centered radical X•. This finding clearly highlights the generality of the recently discovered concept of self-terminating radical oxygenations, through which C≡C triple bonds may be converted into carbonyl groups under very mild reaction conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

10 pages, 2 figures, 2 tables, 7 schemes.-- PMID: 12816493 [PubMed].-- Printed version published Jun 27, 2003., The β-fragmentation of primary alkoxyl radicals, described in many cases as low-yielding and plagued by side reactions, can proceed in satisfactory yields using carbohydrate substrates. The only reaction that can compete significantly with the β-scission is the intramolecular hydrogen abstraction. The ratio of β-fragmentation to hydrogen abstraction can be varied according to the reaction conditions, the stereochemistry of the substituents (e.g., α- or β-anomeric substituents), and the protecting groups chosen. The carbohydrate substrates are easily prepared, and the mild reaction conditions are compatible with most functional groups. The β-scission reaction provides an expedient way toward shorter and less common sugar series and also toward α,ω-differently substituted cyclic ethers. These units are useful building blocks and are present in many natural products with interesting biological activity., This work was supported by the Investigation Programmes PB96-1461 and PPQ2000-0728 of the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Dirección General de Investigación, Ministerio de Ciencia y Tecnología, Spain. We also thank the financial support from FEDER funds. D.H. thanks C.S.I.C.-Comunidad de Canarias for a fellowship.

The oxidation of proteins by free radicals is thought to play a major role in many oxidative processes within cells and is implicated in a number of human diseases as well as ageing. This review summarises information on the formation of radicals on peptides and proteins and how radical damage may be propagated and transferred within protein structures. The emphasis of this article is primarily on the deleterious actions of radicals generated on proteins, and their mechanisms of action, rather than on enzymatic systems where radicals are deliberately formed as transient intermediates. The final section of this review examines the control of protein oxidation and how such damage might be limited by antioxidants.

The autoxidation of six esters, neopentyl butanoate, 2,2-dimethylpropanoate, 3,3-dimethylbutanoate, 2,2-dimethylbutanoate, 2-methylbutanoate and 1,1-[2H2]-neopentyl butanoate, has been studied at 438 K. The reaction products were determined for each system and key reactions leading to the formation and further reactions of the primary products have been identified.Primary products include a range of hydroperoxides which lead to the formation of keto- and hydroxy-esters. Large amounts of neopentanol and the parent carboxylic acid are formed from each ester. It is shown that these are principally oxidation, and not hydrolysis, products.The relative rates of autoxidation of the first five esters mirror the relative rates of attack that occur on reaction with alkoxyl radicals; the sites of attack are on both the alkyl and acyl groups, with the α-alkyl hydrogen atoms on the ester showing particular vulnerability compared to the acyl hydrogen atoms. The analysis of products from the deuterated ester supports this conclusion. p

A variety of acyclic and carbocyclic α-azido-β-keto esters have been readily prepared from the parent dicarbonyl compounds, and their radical chain reactions with tributyltin hydride have been investigated. These reactions normally result in efficient production of alkoxycarbonyl-substituted amides and lactams and thence provide a new, useful method for regiospecific nitrogen insertion of keto ester compounds. The likely mechanism entails initial addition of tributylstannyl radical to the azido moiety to give a stannylaminyl radical, which readily undergoes intramolecular three-membered cyclization onto the ketone group to form an alkoxyl radical. The alkoxyl radical then undergoes regiospecific β-scission to form a stable ring-opened radical that is eventually reduced by tributyltin hydride to propagate the chain. With certain substrates, concomitant deazidation occurs to an important extent. This process, which is unusually observed in radical reactions of alkyl azides, is ascribed to addition of the st...

The paper describes a new source of surface organic radicals whose special feature is a low rate of the initiation of alkyl radicals in reactions of H atoms with the surface of alkanes. A special reactor design was used to accumulate radicals at room temperature and observe alkoxyl radicals RO by the EPR method. For this purpose, alkanes were deposited on aerosil and placed into an EPR cavity. Thanks to the large area of aerosil loads (∼103 cm2), we were able to obtain a stable signal corresponding to a ∼1017 total amount of alkoxyl radicals (the degree of surface coverage ∼0.1%). When O2 was introduced into the reactor in concentrations of 1015–1016 cm−3, a sharp decrease in the signal from surface organic radicals was observed. The process was described as the first-order (RO)s + O2 → HO2 + ketone reaction with a 1.7 × 10−17 cm3 s−1 rate constant.

This paper describes the δ-carbonylation of saturated alcohols which uses a 1,5-hydrogen-transfer reaction of alkoxyl radicals and subsequent carbonylation at the δ-carbon atoms as the key. The carbonylation reactions of five classes of saturated alcohols, namely, primary alcohols having primary δ-carbons, primary alcohols having secondary δ-carbons, primary alcohols having tertiary δ-carbons, secondary alcohols having primary δ-carbons, secondary alcohols having secondary δ-carbons, were carried out, in which lead tetraacetate (LTA) was used as a one-electron oxidant to generate the alkoxyl radicals. Carbonylation of these saturated alcohols, except for primary alcohols having tertiary δ-carbons, took place to afford δ-lactones in moderate to good yields. The mechanism of the remote carbonylation likely involves (1) alkoxyl radical generation via LTA oxidation of a saturated alcohol, (2) conversion of this alkoxyl radical to a δ-hydroxyalkyl radical by a 1,5-hydrogen-transfer reaction, (3) CO trapping of...

Nitrate esters, prepared by treatment of β-hydroxy-α-amino acid derivatives with nitric acid, react with tributyltin hydride to give the corresponding alkoxyl radicals. These radicals readily undergo β-scission, providing a convenient route for the regiocontrolled production of α-carbon-centred amino acid radicals. By examining the partitioning of the alkoxyl radicals between the β-scission process and the competing hydrogen transfer reaction, it has been possible to evaluate the influence of electronic and steric effects on the β-scission reaction and the formation of the carbon-centred radicals.

Alkoxyl radicals have unique characteristic properties such as a facile β-fragmentation and a hydrogen abstraction due to their high reactivity. Various alkoxyl radical precursors are normally prepared from alcohols and include nitrites, nitrates, hypohalites, sulfenyl ethers, and Nalkoxyphthalimides. Especially, N-alkoxypyridine-2thiones 3 have attracted a great deal of attention as synthetically useful alkoxyl radical precursors. However, preparations of N-alkoxypyridine-2-thiones 3 are problematic due to competing Oand S-alkylation (eq. 1). Even under carefully controlled conditions, the desired product 3 is normally obtained in poor yields with a significant amount of undesired S-alkylated side product 4. In addition, the radical precursor is also unstable in light. Thus, some improved procedures have been reported, but the chemical yields were not very high. Since radical precursors are needed to be stable for safe handling and better chemical yields, we have been interested in N-alkoxy-2-pyridones 5 as new alkoxyl radical precursors.

A novel fluorogenic probe for tert-butoxy radicals based on the hydrazino-naphthalimide system is reported. Interestingly, different regioisomers exhibited significantly different optical properties toward ROS, which suggested 4-hydrazinyl naphthalimide as a potential new platform for the in vitro and in cellulo detection of alkoxyl radicals.

Substituted 5-hexen-1-oxyl radicals have been generated from N -(5-hexen-1-oxy)-5-( p -methoxyphenyl)-4-methylthiazole-2(3 H )-thiones under tin-free conditions and have been successfully applied as reactive intermediates in a mechanistic study on the formation of bromomethyl-substituted tetrahydropyrans via 6- exo - trig selective cyclizations.

A time-resolved kinetic study on the effect of metal ions (M(n+)) on hydrogen abstraction reactions from C-H donor substrates by the cumyloxyl radical (CumO(•)) was carried out in acetonitrile. Metal salt addition was observed to increase the CumO(•) β-scission rate constant in the order Li(+)Mg(2+)Na(+). These effects were explained in terms of the stabilization of the β-scission transition state determined by Lewis acid-base interactions between M(n+) and the radical. When hydrogen abstraction from 1,4-cyclohexadiene was studied in the presence of LiClO(4) and Mg(ClO(4))(2), a slight increase in rate constant (k(H)) was observed indicating that interaction between M(n+) and CumO(•) can also influence, although to a limited extent, the hydrogen abstraction reactivity of alkoxyl radicals. With Lewis basic C-H donors such as THF and tertiary amines, a decrease in k(H) with increasing Lewis acidity of M(n+) was observed (k(H)(MeCN)k(H)(Li(+))k(H)(Mg(2+))). This behavior was explained in terms of the stronger Lewis acid-base interaction of M(n+) with the substrate as compared to the radical. This interaction reduces the degree of overlap between the α-C-H σ* orbital and a heteroatom lone-pair, increasing the C-H BDE and destabilizing the carbon centered radical formed after abstraction. With tertiary amines, a2-order of magnitude decrease in k(H) was measured after Mg(ClO(4))(2) addition up to a 1.5:1 amine/Mg(ClO(4))(2) ratio. At higher amine concentrations, very similar k(H) values were measured with and without Mg(ClO(4))(2). These results clearly show that with strong Lewis basic substrates variations in the nature and concentration of M(n+) can dramatically influence k(H), allowing for a fine control of the substrate hydrogen atom donor ability, thus providing a convenient method for C-H deactivation. The implications and generality of these findings are discussed.

Reaction of polyunsaturated fatty acid hydroperoxides with metal complexes generates lipid alkoxyl radicals and metal-oxo complexes. Lipid alkoxyl radicals are presumed to be the species responsible for metal-amplified lipid peroxidation because of the chemical analogy of simple organic alkoxyl radicals to the hydroxyl radical. However, polyunsaturated fatty acid alkoxyl radicals exhibit a rich and diverse chemistry that is dominated by intramolecular cyclization to epoxyallylic radicals. Studies described herein demonstrate that the equilibrium between cyclization and ring-opening of epoxyallylic radicals lies overwhelmingly toward cyclization. Thus lipid alkoxyl radicals have a steady-state concentration that is so low that their contribution to metal-amplified lipid peroxidation is insignificant. In fact, the species responsible for metal amplification of lipid peroxidation appears to be the epoxyperoxyl radical formed by coupling the epoxyallylic radical to molecular oxygen.

Biologically/medicinally important compounds, when metabolized, can generate free radicals from which electronically excited products—often in the triplet state—are generated. Peroxidases are particularly apt to catalyze such processes, which usually entail oxidations by electron transfer. In the latter case, the chemiluminescence may derive from peroxyl and alkoxyl radicals or excited states derived from dioxetanes. Besides peroxidases, prostaglandin-H synthase and lipoxygenase may catalyze the formation of excited carbonyls. The pronounced similarity in the chemical behavior and reactivity of radicals and excited species derives in part from the biradical nature of the latter. Usually in analyzing the biological effects of xenobiotics, only radicals and/or reactive ground state products have been considered. However, in such processes the generation of excited species is possible, which should be tested for by direct and/or sensitized emission or by photochemical transformation.

The visible and UV absorptions of a variety of alkoxyl radicals have been examined by experiment and theory. In most solvents, the tert-butoxyl radical shows only a weak "tail-end" absorption in the UV region of the spectrum and no absorption in the visible region. However, a visible absorption band has been observed (λmax = 440 nm) in the presence of 1,3,5-trimethoxybenzene. This absorption band provides the first unequivocal evidence for the existence of alkoxyl radical/electron-rich aromatic π-complexes. By way of contrast, a solvent-independent absorption in the visible is observed for (arylcarbinyl)oxyl radicals, e.g., benzyloxyl (λmax = 460 nm, ∈ = 1300 M-1 cm-1) and cumyloxyl (λmax = 485 nm, ∈ = 1300 M- cm-1). Electron-donating substituents on the aromatic ring shift the visible absorption to the red by 25-30 nm for a 4-methyl group and by 100-105 nm for a 4-methoxy group. However, α-substitution has only a minor effect on λmax, e.g., 530 and 535 nm for diphenylmethoxyl and 1,1-diphenylethoxyl, respectively. The visible absorption appears to be virtually uninfluenced by the (calculated) magnitude of the dihedral angle, θ, between the C-O. bond and the plane of the aromatic ring, e.g., indan-1-oxyl, θ ∼ 51°, λmax = 530 nm, and Tetralin-1-oxyl, θ ∼ 33° (major conformer), λmax = 520 nm, vs benzyloxyl and cumyloxyl, both of which have θ ∼ 0°. All of these experimental observations are well-matched by theory, which reveals that the visible absorptions of (arylcarbinyl)oxyl radicals are due to D0(A″) → D2(A″) (π → π*) transitions which increase the negative charge on the oxygen atom and have respectable oscillator strengths. The unpaired electron is largely localized in the oxygen 2p orbital which is perpendicular to the plane of the aromatic ring.

A strategy for comparing the 1,5- and 1,6-cyclisation reactions of 3-phenylpropan-1-oxyl radicals is described. Iron(II)-catalysed reduction of 3-(p-methylphenyl)prop-1-yl hydroperoxide and its para-chloro and para-methoxy-substituted analogues, carried out in the presence of copper(II), has been found to give in each case the appropriate para-substituted 3-phenylpropan-1-ol, 3-phenylpropanal and a low yield of a mixture of isomeric 6- and 7-substituted chromans. The alcohols are proposed to form via reduction of either the hydroperoxide or the resulting alkoxyl radical or its cyclised intermediates, and the aldehydes as a result of rearrangement of the alkoxyl radical to an α-hydroxy alkyl radical which subsequently undergoes oxidation. The 7-substituted chromans, which arise directly from 1,6-cyclisation of the alkoxyl radical, were found to dominate the 6-substituted isomers which result from rearrangement of 1,5-cyclised intermediates. This effect is attributed to inefficient interception of the 1,5-cyclised radical intermediate which permits equilibration to the thermodynamically more stable 1,6-cyclised radical isomer to occur. The effect of pH on the reactions has been investigated and although no products typical of the intermediary of aryl radical rations were detected (even under highly acidic conditions), the formation of such intermediates cannot be excluded. Semiempirical MO calculations have been carried out (at the PM3 level of approximation) on a series of model compounds, yielding results which have clarified our understanding of the effect of substituents on the stabilities of the various intermediates arising from the cyclisation reactions of 3-phenylpropan-1-oxyl radicals. Furthermore, these calculations have supported our assumptions regarding the probability and specificity of rearrangements of the spirodienyl intermediates.

This article reviews the progress in the area of radicals in carbohydrate chemistry with special attention to new developments published during the past decade. No attempt has been made to present a comprehensive review of the literature but, rather, some specific examples are given to highlight the most synthetically valuable processes. The major focus is on inter- and intramolecular carbon–carbon bond-forming radical reactions, with emphasis on the preparation of C-glycosides, C-ketosides, C-disaccharides, and branched-chain sugars, as well as on the synthesis of polyfunctionalized carbocycles by radical cyclization of acyclic carbohydrate derivatives. We also describe methods for the formation of carbon–hydrogen bonds, and synthesis in which a heteroatom-centered radical plays a clear role in the carbon–heteroatom (C–N, C–P, C–O, C–S/Se, and C–Br) bond formation. Finally, a few selected examples of alkoxyl radical β-fragmentation reactions, carried out under oxidative or reductive conditions, are included to illustrate their potential in the preparation of chiral synthons. Keywords: carbohydrates; radicals; C-glycosides; C-disaccharides; carbasugars; glycos-1-yl radicals; carbon-centered radicals; heteroatom-centered radicals

Resveratrol (trans-3, 5, 4'-trihydroxystilbene), a natural compound has attracted considerable interest because of its biological activities against a collection of diseases. The cancer chemoprevention effects of resveratrol has been related to its antioxidant activity, because free radical mediated peroxidation of membrane lipids and ensuing oxidative damage are assumed to play a causative role in cancer. However, it is somewhat surprising that spectral and kinetic data of the transient and mechanism of resveratrol reaction with most relevant radical species are scarce, particularly with alkoxyl radicals which are well known mediators in lipid peroxidation process. The chain-breaking ability of polyphenols is referred to the ease of the donation of the phenolic H-atom to the attacking free radical. At the same time, H-atom abstraction is probably the best known chemical reaction of aromatic carbonyl triplets which are particularly interesting in biological systems since their excited states can be produced in vivo. It was pointed out that triplet carbonyls with n*character behave like alkoxyl radicals and can thus initiate several chain reactions, including lipid peroxidation. The present study uses an efficient generation of tert-butoxyl radicals (t-BuO●) to provide spectroscopic and kinetic data regarding the reactivity of resveratrol toward t-BuO●. The rate constant was determined under pseudo-first order conditions in acetonitrile solutions at room temperature. The t-BuO● radicals were generated directly by homolytic photodecomposition of di-tert-butyl peroxide using laser flash photolysis. The rate constant was determined by measuring the phenoxyl radical formation rate at 390 nm as function of resveratrol concentration in acetonitrile. The rate constant was determined to be 6.5 × 108 M−1 s−1. In view of the fact that n* triplets present many similarities with alkoxyl radicals in their hydrogen abstraction reactions, a comparison between the kinetics of t-BuO● radicals and the benzophenone triplet state in respect of their reactions with resveratrol will be presented.

The fragmentation of anomeric alkoxyl radicals (ARF) and the subsequent intramolecular cyclization promoted by hypervalent iodine reagents provide an excellent method for the synthesis of tetrazolo-sugars. This new reaction offers additional advantages for the synthesis of these compounds, including the ready availability of the starting materials, experimental simplicity, mild conditions, and good yields., This work was supported by the Gobierno de Canarias (Research Program ProID20100088) and the investigation program no. CTQ2007-67492/BQU of the Ministerio de Educación y Ciencia (Spain) cofinanced with the Fondo Europeo de Desarrollo Regional (FEDER). A.G.S. thanks the I3P-CSIC Program for a fellowship.

The reaction of Artemisinin with solvated electrons ( e solv - ) generated by radiolytic methods led to the formation of acid 2 as the only detectable product. A possible mechanism leading to the formation of compound 2 is discussed.

Acetyl hypoiodite and a number of alkyl hypoiodites have been characterized as intermediates in the conversion of alcohols into alkoxyl radicals under Suarez (photostimulated iodosobenzenediactetate/iodine reagent) and Beebe (photolysed acetyl hypoiodite/alcohol) conditions.

Experimental data on the activation energies of reactions of H-abstraction from oxygencontaining compounds by oxygen atoms and hydroxyl and alkoxyl radicals in the gas and liquid phases have been analyzed by means of the parabolic model of the transition state. The contribution of polar interaction to the activation energies of the reactions has been calculated. The contribution of solvation to the activation energy has been calculated by comparison of the reaction parameters of the respective reaction in the liquid and gas phases.

WOS:000300684800012; International audience; no abstract

Resveratrol (trans-3, 5, 4'-trihydroxystilbene), a plant-derived compound, has attracted much attention during the last years due to the simplicity of its structure and its low toxicity in vivo systems. The cancer chemoprevention effects of resveratrol might be traced back to its antioxidant activity, because free radical mediated peroxidation of membrane lipids and oxidative damage are assumed to play a causative role in cancer. The relation of radical-scavenging activity of resveratrol and its analogues to their structure has been studied.1, 2 However, spectral and kinetic data of the reaction and mechanism of resveratrol with the most relevant radical species are scarce, particularly with alkoxyl and thiyl radicals which are biologically very important. Alkoxyl radicals are well known mediators in lipid peroxidation process and propagators of the chain free radical reactions in lipids, while thiyl radicals protect lipids against degradation. The present study aims to achieve an efficient generation of alkoxyl and thiyl radicals and to provide spectroscopic and kinetic data regarding the reactivity of resveratrol towards each of the generated radicals. The t-butoxyl radicals were generated directly from t-butylperoxide by peroxide bond cleavage using Nd:YAG laser at 355 nm.2, 3 The rate constant for the reaction of t-butoxyl radicals with resveratrol was studied under pseudo-first order conditions. The rate constant was determined by measuring the phenoxyl radical formation rate at about 390 nm as function of resveratrol concentration. The rate constant of the reaction of t-butoxyl radicals with resveratrol in acetonitrile was determined to be 6.5 × 108 M-1 s-1. Thiyl radicals could be generated indirectly by using a photosentizer benzophenone4 after the 347 nm ruby laser pulse. The existing set-up and the procedure of resolving the transient spectra allowed us to obtain the optimum concentration profiles of transient species formed under chosen conditions.

Plant derived resveratrol (trans-3, 5, 4'-trihydroxystilbene) possesses a broad spectrum of biological activities, one of them are very well known its antioxidative properties [1]. Our work aims to provide kinetic data with regard to the reactivity of resveratrol with uninvestigated short-lived bioradicals, identified as mediators in oxidative lipid degradation processes. Radicals of our interest are alkoxyl radicals, well known propagators of the chain free radical reactions in lipids, and thiyl radicals which protect lipids from their degradation pathway, but at the same time cause the isomerization of the double bonds. In order to investigate these reactions of resveratrol laser flash photolysis was used. On the basis of competitive kinetics the rate constants were determined under pseudo-first order conditions in acetonitrile solutions at room temperature. Thiyl radicals were generated indirectly in solution containing 1-octadecanthiol and photosensitive benzophenone in acetonitrile using the light pulses at 347 nm from ruby laser. Tert-butoxyl radicals were generated directly by peroxide bond cleavage from di-tert-butyl peroxide in acetonitrile by light pulses of Nd:YAG at 355 nm [2], and ruby at 347 nm [3]. Obtained rate constants for the reactions of resveratrol and radicals generated by laser flash photolysis will be summarized and compared with rare literature data for the rate constants of investigated reactions of resveratrol and other radicals generated by pulse radiolysis.

EPR spectroscopic observations and product studies showed that the trimethylsilyl group undergoes 1,2-migration from carbon to nitrogen in aminyl radicals, Me 3 SiCh 2 O . → . CH 2 NHSiMe 3 , and from carbon to oxygen in alkoxyl radicals, Me 3 SiCh 2 O . → . CH 2 OSiMe 3 .

A new transformation of steroids into 18-norsteroids under mild conditions is described. The key step was a regioselective β-scission of the alkoxyl radicals generated by photolysis of the hypoiodite of 18-hydroxy-18,20α-epoxy steroids, prepared by photolysis of steroidal 20α-ol nitrites followed by deoximation of the resulting 18-hydroxyimino-20α-hydroxy steroid with sodium nitrite and acetic acid. 3β-Hydroxypregn-5-en-20-one (pregnenolone) was thus transformed into 3β-hydroxy-18-norpregna-5,13-dien-20-one (12-deoxofukujusonorone) in 10 steps.

The synthesis of several unsaturated 3-oxasteroids and 4a-homo-4-oxasteroids of cholestane series functionalized at their B-ring is described; 3β-hydroxycholest-5-en-7-one and its 4,4-dimethyl derivative were transformed into 3-oxacholest-5-en-7-one and its 4,4-dimethyl derivative in two or three steps involving a regioselective β-scission of the corresponding alkoxyl radicals (generated by irradiating their hypoiodites in benzene) as the key step. The formation of 2-iodo-7-oxo-4-nor-2,3-secocholest-5-en-3-yl formate by irradiation of the hypoiodite of 3β-hydroxycholest-5-en-7-one was accompanied by the formation of a product arising from a new ring contraction of the A-ring. The ring-contraction mechanism is discussed.

A time-resolved kinetic study on the reactions of the tert-butoxyl (t-BuO*), cumyloxyl (CumO*), and benzyloxyl (BnO*) radicals with alkylferrocenes has been carried out in MeCN solution. With all radicals, clear evidence for an electron transfer (ET) process has been obtained, and with the same ferrocene donor, the reactivity has been observed to increase in the order t-BuO*CumO*BnO*, with the difference in reactivity approaching 3 orders of magnitude on going from t-BuO* to BnO*. With BnO*, an excellent fit to the Marcus equation has been obtained, from which a value of the reduction potential of BnO* (E degrees(BnO*/BnO(-)) = 0.54 V/SCE) has been derived. The latter value appears, however, to be significantly higher than the previously determined reduction potential values for alkoxyl radicals and in contrast with the differences in the computed solution-phase electron affinities determined for t-BuO*, CumO*, and BnO*, indicating that the reaction of BnO* with ferrocene donors may not be described in terms of a straightforward outer sphere ET mechanism. From these data, and taking into account the available value of the reduction potential for CumO*, a value of E degrees (BnO*/BnO(-)) = -0.10 V/SCE has been estimated. On the basis of computational evidence for the formation of a pi-stacked prereaction complex in the reaction between BnO* and DcMFc, an alternative ET mechanism is proposed for the reactions of both CumO* and BnO*. In these cases, the delocalized nature of the unpaired electron allows for the aromatic ring to act as an electron relay by mediating the ET from the ferrocene donor to the formal oxygen radical center. This hypothesis is also in line with the observation that both BnO* and CumO* react with the ferrocene donors with rate constants that are in all cases at least 2 orders of magnitude higher than those measured for t-BuO*, wherein the radical is well-localized.

Reaction of polyunsaturated fatty acid hydroperoxides with metal complexes generates lipid alkoxyl radicals and metal-oxo complexes. Lipid alkoxyl radicals are presumed to be the species responsible for metal-amplified lipid peroxidation because of the chemical analogy of simple organic alkoxyl radicals to the hydroxyl radical. However, polyunsaturated fatty acid alkoxyl radicals exhibit a rich and diverse chemistry that is dominated by intramolecular cyclization to epoxyallylic radicals. Studies described herein demonstrate that the equilibrium between cyclization and ring-opening of epoxyallylic radicals lies overwhelmingly toward cyclization. Thus lipid alkoxyl radicals have a steady-state concentration that is so low that their contribution to metal-amplified lipid peroxidation is insignificant. In fact, the species responsible for metal amplification of lipid peroxidation appears to be the epoxyperoxyl radical formed by coupling the epoxyallylic radical to molecular oxygen.

Nitrate esters, prepared by treatment of β-hydroxy-α-amino acid derivatives with nitric acid, react with tributyltin hydride to give the corresponding alkoxyl radicals. These radicals readily undergo β-scission, providing a convenient route for the regiocontrolled production of α-carbon-centred amino acid radicals. By examining the partitioning of the alkoxyl radicals between the β-scission process and the competing hydrogen transfer reaction, it has been possible to evaluate the influence of electronic and steric effects on the β-scission reaction and the formation of the carbon-centred radicals.

This paper describes the δ-carbonylation of saturated alcohols which uses a 1,5-hydrogen-transfer reaction of alkoxyl radicals and subsequent carbonylation at the δ-carbon atoms as the key. The carbonylation reactions of five classes of saturated alcohols, namely, primary alcohols having primary δ-carbons, primary alcohols having secondary δ-carbons, primary alcohols having tertiary δ-carbons, secondary alcohols having primary δ-carbons, secondary alcohols having secondary δ-carbons, were carried out, in which lead tetraacetate (LTA) was used as a one-electron oxidant to generate the alkoxyl radicals. Carbonylation of these saturated alcohols, except for primary alcohols having tertiary δ-carbons, took place to afford δ-lactones in moderate to good yields. The mechanism of the remote carbonylation likely involves (1) alkoxyl radical generation via LTA oxidation of a saturated alcohol, (2) conversion of this alkoxyl radical to a δ-hydroxyalkyl radical by a 1,5-hydrogen-transfer reaction, (3) CO trapping of...

The rates and selectivities of the hydrogen-atom abstraction reactions of electrically-neutral free radicals are known to depend on polar effects which operate in the transition state. Thus, an electrophilic species such as an alkoxyl radical abstracts hydrogen much more readily from an electron-rich C–H bond than from an electron-deficient one of similar strength. The basis of polarity-reversal catalysis (PRC) is to replace a single-step abstraction, that is slow because of unfavourable polar effects, with a two-step process in which the radicals and substrates are polarity-matched. This review explores the concept of PRC and describes its application in a variety of situations relevant to mechanistic and synthetic organic chemistry.

In a comparative study, reactions between 5-(p-methoxyphenyl)-substituted 3-alkoxy-4-methylthiazole-2(3H)-thiones and appropriate mediators (BrCCl3, Bu3SnH) provided higher yields of alkoxyl radical products (δ-bromohydrins, cyclic ethers, carbonyl compounds) than respective transformations of 5-phenyl- and 5-methyl-substituted derivatives. The unusual selectivity of applied thiohydroxamates to furnish products of O-alkylation, even upon treatment with soft carbon electrophiles, and the marked propensity of 3-alkoxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3H)-thiones to crystallize, facilitated preparation and purification of the new family of alkoxyl radical precursors in a noteworthy manner.

A variety of acyclic and carbocyclic α-azido-β-keto esters have been readily prepared from the parent dicarbonyl compounds, and their radical chain reactions with tributyltin hydride have been investigated. These reactions normally result in efficient production of alkoxycarbonyl-substituted amides and lactams and thence provide a new, useful method for regiospecific nitrogen insertion of keto ester compounds. The likely mechanism entails initial addition of tributylstannyl radical to the azido moiety to give a stannylaminyl radical, which readily undergoes intramolecular three-membered cyclization onto the ketone group to form an alkoxyl radical. The alkoxyl radical then undergoes regiospecific β-scission to form a stable ring-opened radical that is eventually reduced by tributyltin hydride to propagate the chain. With certain substrates, concomitant deazidation occurs to an important extent. This process, which is unusually observed in radical reactions of alkyl azides, is ascribed to addition of the st...

Photolysis of substituted N-alkoxythiazolethiones 1 in aqueous solvents furnishes alkoxyl radicals 2, which, upon stereoselective 5-exo-trig cyclization, are trapped by water soluble thiols (L-cysteine, L-cysteine ethyl ester, or the reduced form of glutathione, GSH) to afford disubstituted tetrahydrofurans 3 in synthetically useful yields and with satisfactory to excellent diastereoselectivities.

The β-fragmentation of alkoxyl radicals derived from easily available carbohydrates is a mild and efficient procedure to obtain unsymmetrical α,ω-disubstituted cyclic ethers.

The representative photostimulated hypoiodite reaction of cyclopentanol with mercury(II) oxide and iodien gives products formed by a sequence of iodoaldehyde formation, followed by consumption to give Baeyer-Villiger and hydrolysis products.