Radical cyclization in heterocycle synthesis 15. Relationship between a Radical species and radical acceptors of three different types of double bond in radical addition-cyclization

Relationship between a radical species and radical acceptors of three different types of double bond in radical addition-cyclization was systematically investigated. Substrates carrying alpha,beta-unsaturated amide, isolated olefin, and oxime ether moieties underwent radical addition-cyclization to give differently substituted lactams depending upon the radicals used. The sulfanyl radical addition-cyclization of the substrate proceeded smoothly to give the 5-membered lactam having an alkoxyamino group as a result of preferable addition of an intermediary alpha-carbonyl radical to the oxime ether. On the other hand, the triethylborane-mediated radical addition-cyclization gave the lactam bearing an iodomethyl group as a result of addition to an intermediary alpha-carbonyl radical to isolated olefin. The different regioselectivity was explained by the stability of the intermediary radical and the interaction between SOMO and HOMO.     

Radical addition of alkyl halides to formaldehyde in the presence of cyanoborohydride as a radical mediator. A new protocol for hydroxymethylation reaction

Hydroxymethylation of alkyl halides was achieved using paraformaldehyde as a radical C1 synthon in the presence of tetrabutylammonium cyanoborohydride as a hydrogen source. The reaction proceeds via a radical chain mechanism involving an alkyl radical addition to formaldehyde to form an alkoxy radical, which abstracts hydrogen from a hydroborate anion.     

A formal synthesis of martinelline via a combination of two types of radical reactions

A formal synthesis of martinelline has been accomplished via two types of radical reactions as the key steps. These are the radical addition-cyclization-elimination of an oxime ether carrying an unsaturated ester and a C-C bond formation through a radical 1,5-hydrogen atom translocation.     

丙烯与HBr/Br·发生自由基加成和取代反应的机理和竞争

含有α-H的烯烃可以与溴自由基发生自由基加成和自由基取代反应。本文以丙烯为例,论述了自由基加成和取代反应的机理和竞争关系,从而帮助读者更好地理解反应条件对优势反应及产物的影响。     

Radical heterolysis reactions. Dynamics of formation, collapse, and solvation of ion pairs determined by a competition kinetic method

The kinetics of radical heterolysis reactions, including rate constants for radical cation-anion contact ion pair formation, collapse of the contact pair back to the parent radical, and separation of the contact pair to a solvent-separated ion pair or free ions were obtained in several solvents for a beta-mesyloxy radical. Rate constants were determined from indirect kinetic studies using thiophenol as both a radical trapping agent via H-atom transfer and an alkene radical cation trapping agent via electron transfer. [reaction: see text].     

High performance liquid chromatography/electron spin resonance/mass spectrometry analyses of radicals formed in an anaerobic reaction of 9- (or 13-) hydroperoxide octadecadienoic acids with ferrous ions

The oxidation of linoleic acid yields isomeric acyl hydroperoxides. In order to clarify the relation between the lipid peroxide-derived radicals and the toxicity of the lipid peroxide, identification of the lipid-derived radicals is essential. In this paper, high performance liquid chromatography/electron spin resonance/mass spectrometry (HPLC/EPR/MS) analysis of the radicals was performed for the reaction mixture containing 9-hydroperoxy-(10E,12E)-octadeca-10,12-dienoic acid (9EE-OOH) [or 13-hydroperoxy-(9Z,11E)-octadeca-9,11-dienoic acid (13ZE-OOH)] under an aerobic condition or an anaerobic condition. Following radicals were identified from 9EE-OOH (or 13EZ-OOH) by using high performance liquid chromatography/electron spin resonance spectrometry (HPLC/EPR) and HPLC/EPR/MS: pentyl radical and isomers of epoxylinoleic acid radicals from 13EZ-OOH under an anaerobic condition; 7-carboxyheptyl radical and pentyl radical from 13EZ-OOH under an aerobic condition; 7-carboxyheptyl radical and pentyl radical from 9EE-OOH under an aerobic condition; 7-carboxyheptyl radical from 9EE-OOH under an anaerobic condition. These results showed that the formation of the respective radical species depends on oxygen concentration in the reaction mixtures to a great extent.     

Anthralin: primary products of its redox reactions

One-electron reduction significantly enhances the ability of anthralin, 1, to act as a hydrogen atom donor. On annealing of an MTHF glass in which the radical anion of anthralin, 1*-, is generated radiolytically, this species decays mainly by loss of H* to give the anthralyl anion, 2- . On the other hand, radicals formed on radiolysis of matrices that are suitable for the generation of radical anions or cations are capable to abstract H* from anthralin to give the anthralyl radical, 2* . Both 2- and 2* are obtained simultaneously by mesolytic cleavage of the radical anion of the anthralin dimer. Contrary to general assumptions, the anthralyl radical is found to be much more reactive toward oxygen than the anion. All intermediates are characterized spectroscopically and by reference to quantum chemical calculations. Attempts to generate the radical cation of anthralin by X-irradiation of an Ar matrix containing anthralin led also to significant formation of its radical anion, i.e., anthralin acts apparently as an efficient electron trap in such experiments.     

Use of a conformational radical clock for evaluating alkyllithium-mediated cyclization reactions

The reductive lithiation of nitrile 9 led to the cyclic product 11 as a single diastereomer in 42% ee. The intermediate radical is a conformational radical clock. The radical lifetime can be determined from the optical purity of the product 11. We show that the lifetime of the intermediate radical is too brief to allow a radical cyclization, and thus the cyclization proceeds through an alkyllithium intermediate.     

Suicide inactivation of dioldehydratase by glycolaldehyde and chloroacetaldehyde: an examination of the reaction mechanism

High-level ab initio calculations have been used to study the mechanism for the inactivation of diol dehydratase (DDH) by glycolaldehyde or 2-chloroacetaldehyde. As in the case of the catalytic substrates of DDH, e.g., ethane-1,2-diol, the 5'-deoxyadenosyl radical (Ado*) is able to abstract a hydrogen atom from both substrate analogues in the initial step on the reaction pathway, as evidenced by comparable energy barriers. However, in subsequent step(s), each substrate analogue produces the highly stable glycolaldehyde radical. The barrier for hydrogen atom reabstraction by the glycolaldehyde radical is calculated to be too high ( approximately 110 kJ mol-1) to allow Ado* to be regenerated and recombine with the cob(II)alamin radical, the latter therefore remaining tightly bound to DDH. As a consequence, the catalytic pathway is disrupted, and DDH becomes an impotent enzyme. Interconversion of equivalent structures of the glycolaldehyde radical via the symmetrical cis-ethanesemidione radical is calculated to require 38 kJ mol-1. EPR indications of a symmetrical cis-ethanesemidione structure are likely to be the result of formation of an equilibrium mixture of glycolaldehyde radical structures, this equilibration being facilitated by partial deprotonation of the glycolaldehyde radical by the carboxylate of an amino acid residue within the active site of DDH.     

Production of radical species and modification of DNA through one-electron reduction with indium metal

Indium metal produced radical species on DNA through one-electron reduction of 5-iodouracil, and DNA modification via a radical intermediate became possible by the use of an aqueous mixture containing both indium and a radical acceptor.     

Studies on organosilicon reactive intermediates VIII synthesis and photochemistry of di(α-thienyl) hexamethyltrisilane

The synthesis of di(α-thienyl)hexamethyltrisilane (1) is described. In the photolysis of 1 with cyclohexene and methanol, an apparent radical reaction occurred. We suspect that the sulfur atom of the thienyl group strongly stabilizes an initially formed silyl radical. This idea was supported both by identifying typical radical reaction products and examining the ESR spectrum of an adduct obtained by use of a radical trap. © 1996 John Wiley & Sons, Inc.     

New generation of organosilyl radicals by photochemically induced homolytic cleavage of silicon-boron bonds

Unlike bis(diethylamino)organosilylboranes, bis(diisopropylamino)organosilylboranes, which have UV absorption at longer wavelength than 300 nm, undergo photolysis to afford pairs of an organosilyl radical and a bis(diisopropylamino)boryl radical by homolytic scission of the silicon-boron bonds. Generation of organosilyl radical and organoboryl radical was confirmed by trapping experiments using TEMPO (2,2,6,6-tetramethylpiperidine N-oxyl). The organosilyl radical thus generated induces not only silylation of mono-olefins and silylative cyclization of dienes but also polymerization to afford polymers bearing organosilyl termini. On the other hand, the bis(diisopropylamino)boryl radical generated is not incorporated into the olefin adducts.     

Radical reactions of epoxy esters induced by titanocene chloride

The reductive radical cyclizations of several epoxy esters have been achieved using titanocene chloride. The tether length from the initial radical to the carbonyl acceptor is the key of the reactions. We obtained products from radical cyclization onto carbonyl formate and products from formate and hydrogen elimination. The stereochemical outcome of the 5-exo radical cyclization of two diastereomers is reported. A radical cascade cyclization of an unsaturated epoxy formate is also described.     

Photochemical reactions of hypericin with alcohols and albumins. Kinetics and mechanism of the primary processes

The photochemical reactions of the hypericin sodium salt with alcohols and albumins yielding the corresponding semiquinone radical were studied by means of microsecond and nanosecond pulse photolysis. The decay of the semiquinone radical follows the second-and first-order rate law for alcohol solutions and the NaHY-albumin system, respectively. The lifetime and the yield of the semiquinone radical decrease in the presence of oxygen. In the oxygen-saturated solutions, the lifetime of the semiquinone radical increases with an increase in the albumin concentration in the solution from 1 to 50 mg/ml. This effect is caused by a decrease in the reactivity of the semiquinone radical toward oxygen due to the steric hindrance created by albumin and is not associated with an increase in the solvent viscosity.     

Charge transfer complexing in the course of triplet state quenching of carbocyanine dyes by nitroxyl radical

Quenching of triplet states of carbocyanine dyes by nitroxyl radical has been investigated by the flash photolysis method. Quenching of triplet state carbocyanine dyes with one polymethyne chain occurs via enhanced intersystem crossing on exchange interaction with the radical. Quenching of triplet state carbocyanine dyes with two polymethyne chains occurs via partial charge transfer in the collision complex with the radical. In the second case, an increase in the dielectric constant of the solvent leads to an increase of the rate of quenching. In high polarity solvents (propanol, methanol) complete electron transfer from dye triplet state to radical occurs. Kinetic and spectral characteristics of a new dye radical (Dye.⁺) are reported.     

The Impact of Resonance Stabilization on the Intramolecular Hydrogen‐Atom Shift Reactions of Hydrocarbon Radicals

A series of intramolecular H‐atom shift reactions of both alkenyl and allylic radicals were investigated by using CBS‐QB3 electronic structure calculations. In the first set of reactions, an alkyl radical site was converted into an allylic radical site. In the second set, an allylic radical was converted into another allylic radical. The results are discussed in the context of a Benson‐type model to examine the impact of the transition‐state partial resonance stabilization on both the activation energies and the pre‐exponential factors. In most cases, the differences in the activation energies relative to those for the analogous alkyl radicals are primarily due to the barriers of the bimolecular reaction component of the activation energy. For the first set of reactions, there is additional entropy loss relative to the alkyl radical analogues. This additional loss of entropy may be smaller than some previous estimates. The pre‐exponential factors for the second set of reactions are generally similar to those of the analogous alkyl radical reactions (once the double bond in the transition state is accounted for).     

One electron oxidation induced dimerization of 5-hydroxytryptophol: role of 5-hydroxy substitution

Reaction of one-electron oxidant (Br(2)(*-)) with tryptophol (TP) and 5-hydroxytryptophol (HTP) have been studied in aqueous solution in the pH range from 3 to 10, employing nanosecond pulse radiolysis technique and the transients detected by kinetic spectrophotometry. One-electron oxidation of TP has produced an indolyl radical that absorbs in the 300-600 nm region with radical pK(a) = 4.9 +/- 0.2, while the reaction with HTP has produced an indoloxyl radical with lambda(max) at 420 nm and radical pK(a) < 3. Hydroxyl radicals ((*)OH) react with these two compounds producing (*)OH radical adducts that undergo water elimination to give one-electron-oxidized indolyl and indoloxyl radical species, respectively. The indoloxyl radicals react with the parent compound to form dimer radicals with an average association constant of (6.7 +/- 0.4) x 10(4) M(-1). No such dimerization is observed with indolyl radical, indicating that the presence of the 5-hydroxy group markedly alters its ability to form a dimer. A possible explanation behind such a difference in reactivity has been supported with ab initio quantum chemical calculations.     

Photosensitized Intermolecular Carboimination of Alkenes through the Persistent Radical Effect

An intermolecular, two‐component vicinal carboimination of alkenes has been accomplished by energy transfer catalysis. Oxime esters of alkyl carboxylic acids were used as bifunctional reagents to generate both alkyl and iminyl radicals. Subsequently, addition of the alkyl radical to an alkene generates a transient radical for selective radical–radical cross‐coupling with the persistent iminyl radical. Furthermore, this process provides direct access to aliphatic primary amines and α‐amino acids by simple hydrolysis.     

Enantioselective cyclization of alkene radical cations

[reaction: see text] Enantiomerically enriched beta-(diphenylphosphatoxy)nitroalkanes undergo radical ionic fragmentation, induced by tributyltin hydride and AIBN in benzene at reflux, to give alkene radical cations in contact radical ion pairs. These contact ion pairs are trapped intramolecularly by amines to give pyrrolidines and piperidines with significant enantioselectivity ( approximately 60% ee), indicative of cyclization competing effectively with equilibration within the ion pairs. Use of an intramolecular N-propargylamine as a nucleophile provides an enantiomerically enriched pyrrolizidine skeleton via a tandem polar/radical crossover sequence.     

Anion radical chain cycloaddition of tethered enones: intramolecular cyclobutanation and Diels-Alder cycloaddition

[reaction: see text] The anion radicals of certain bis(enones), generated by cathodic reduction, are observed to participate in intramolecular cyclobutanation, yielding bicyclo[3.2.0]heptane derivatives through an anion radical chain mechanism. Evidence for stepwise cycloaddition involving distonic anion radical intermediates is presented. In addition to the novel anion radical cyclobutanations, an unprecedented intramolecular anion radical Diels-Alder product is observed. Parallel trends in substrate scope vis-à-vis the Co-catalyzed bis(enone) cyclobutanation are discussed.