N-heterocyclic carbene-catalyzed radical reactions

While N-heterocyclic carbene(NHC)catalyzed electron-pair-transfer processes have been developed into an important tool for synthetically important bond formations during the past decades,the corresponding radical reactions via NHC catalysis have only received growing attention in the past six years.Taking into account the advantages NHC-catalyzed radical reactions might bring,such as creating new activation modes that were previously unobtainable,it is worthwhile to provide a conceptual understanding of this emerging area.Therefore,herein we give an overview of NHC-catalyzed radical reactions via different synthetic techniques.     

How radical cations react? - Distonic radical cation mediated α(nucleophilic), β(radical)-dibenzoloxylation of donor ArCH = CHR

Rate determination and product studies have disclosed that the fragmentation pattern of radical cations 2-propenyl-1,4-dimethoxybenzene (1^{+ ·}) and 2-propenyl-1,4,5-trimethoxybenzene (2^+·) generated in one-electron oxidation of their parent substrates by 4-nitrobenzoyl peroxide (3) in CH₃CN is greatly affected by ring-substitution status of the donor molecules. While ringbenzoloxylation (product 5) predominated in the reaction of dimethoxylated substrate (1), the oxidation of trimethoxylated donor 2 ended up with distonic radical cation mediated ,-di-4-nitrobenzoloxylation as the major pathway.     

Theoretical study on the radical–radical reaction mechanism of CH2I + NO2

The mechanisms of CH₂I with NO₂ reaction were investigated on the singlet and triplet potential energy surfaces (PESs) by the UB3LYP method. The energetic information is further refined at the UCCSD(T) and UQCISD(T) levels of theory. Our results indicated that the title reaction is more favorable on the singlet PES thermodynamically, and less competitive on the triplet one. On the singlet PES, the title reaction is most likely to be initiated by the carbon-to-oxygen approach forming the adduct IM1 (H₂ICONO-trans) without any transition state, which can isomerizes to IM2 (H₂ICNO₂) and IM3 (H₂ICONO-cis), respectively. The most feasible pathway is the 1, 3-I shift with C–I and O–N bonds cleavage along with the N–I bond formation of IM1 lead to the product P1 (CH₂O + INO), which can further dissociate to give P3 (CH₂O + I + NO). The competitive pathway is 1, 3-H shift associated with O–N bond rupture of IM1 to form P2 (CHIO + HNO). The theoretically obtained major product CH₂O and adducts IM1 and IM2 are in good agreement with the kinetic detection in experiment. The similarities and discrepancies between CH₂I + NO₂ and CH₂Br + NO₂ reactions are discussed in terms of the electronegativity of halogen atom and the barrier height of the rate-determining process. The present study may be helpful for further experimental investigation of the title reaction.     

Spectroscopic characterization of alkane radical cations—I. Electronic absorption spectra of 3-methylalkane radical cations

Radical cations of various 3-methylalkanes (C₆-C₁₄) have been produced and stabilized by γ-irradiation of the corresponding neutral compounds in saturated chloroflourocarbon (1,1-diflourotetra-chloroethane and 1,1,2-trichlorotriflouroethane) and perflourocarbon (perflourohexane and perfluoro-methylcyclohexane) matrices at 77 K. The perfluorocarbon matrices appeared more suitable for studies of the lighter radical cations, whereas the chlorofluorocarbon matrices were more suited for studies of the heavier radical cations; intermediary cations could be studied in both types of matrices. After irradiation, electronic absorptions associated with both the matrix and the alkane additive were observed. Pure spectra of the 3-methylalkane radical cations were obtained by difference spectrometry, after selective elimination of these cations by illumination. The electronic absorption spectra of the 3-methylalkane radical cations consist in all cases of a single broad absorption band. The spectral position of this band shifts to longer wavelengths with increasing chain length; the maximum of the absorption band was found to be situated at 490 nm for 3-methylpentane radical cations and at 940 nm for 3-methyltridecane radical cations. The results are most interesting because they give direct information on the electronic absorption of 3-methylpentane radical cations. It was found that the molar extinction coefficients of these cations are not very much smaller than those of other 3-methylalkane radical cations and thus must be of the order of 10³dm³·mol^-1·cm^-1. From this it is deduced that the majority of positive ions trapped in irradiated pure 3-methylpentane glasses at 77 K are not parent cations.     

Are the radical centers in peptide radical cations mobile? The generation, tautomerism, and dissociation of isomeric alpha-carbon-centered triglycine radical cations in the gas phase

The mobility of the radical center in three isomeric triglycine radical cations[G(*)GG](+), [GG(*)G](+), and [GGG(*)](+) has been investigated theoretically via density functional theory (DFT) and experimentally via tandem mass spectrometry. These radical cations were generated by collision-induced dissociations (CIDs) of Cu(II)-containing ternary complexes that contain the tripeptides YGG, GYG, and GGY, respectively (G and Y are the glycine and tyrosine residues, respectively). Dissociative electron transfer within the complexes led to observation of [Y(*)GG](+), [GY(*)G](+), and [GGY(*)](+); CID resulted in cleavage of the tyrosine side chain as p-quinomethide, yielding [G(*)GG](+), [GG(*)G](+), and [GGG(*)](+), respectively. Interconversions between these isomeric triglycine radical cations have relatively high barriers (> or = 44.7 kcal/mol), in support of the thesis that isomerically pure [G(*)GG](+), [GG(*)G](+), and [GGG(*)](+) can be experimentally produced. This is to be contrasted with barriers < 17 kcal/mol that were encountered in the tautomerism of protonated triglycine [Rodriquez C. F. et al. J. Am. Chem. Soc. 2001, 123, 3006-3012]. The CID spectra of [G(*)GG](+), [GG(*)G](+), and [GGG(*)](+) were substantially different, providing experimental proof that initially these ions have distinct structures. DFT calculations showed that direct dissociations are competitive with interconversions followed by dissociation.     

Clean photochemical synthesis mediated by radical-radical reactions: radical buffer or the persistent free radical effect?

[reaction: see text] A new synthetic methodology is reported that takes advantage of the persistent free radical effect (PFRE), where clean products can be obtained in good yields from radical cross-combination reactions, despite their reputation for being of little synthetic value and for resulting in complex mixtures; these problems can be avoided when the PFRE is used as a synthetic tool.     

Hydroxylation of 3-nitrotyrosine by hydroxyl radical

Hydroxylation of 3-nitrotyrosine (3-NT) and 3-NT containing peptide Gly-nitroTyr-Gly in aqueous solution by hydroxyl radical were investigated with gamma irradiation. The structures of the hydroxylated products were confirmed by electrospray ionization mass spectrometry and 1H NMR spectrometry. The reactivity of 3-nitrotyrosine has been investigated using density functional theory (DFT) calculation.     

Charge shift bonding concept in radical π-dimers

We show that pancake bonding in radical π-dimers display features of charge shift (CS) bonding. While the CS bonding concept has been developed to interpret the unusual aspects of σ-bonds around centers with a large number of lone pairs, such as F(2) and HOOH, we find a similar role played by the nonbonding or slightly bonding π-electron pairs in π-stacking radical dimers. Arguments and computational evidence indicate that the CS bonding concept developed by Shaik and Hiberty et al. captures essential features of the intermolecular bonding in radical π-dimers in which the overlap of the two radical centered singly occupied molecular orbitals (SOMOs) play a crucial role. By using the tetracyanoethylene anion dimer, [TCNE](2)(2-), as a model, we show that compared to CAS(2,2) calculations, significant binding contributions are recovered in the calculations simply by including selected intrapair excitations of the SOMO-SOMO bonding orbitals and the nonbonding π-orbitals. This observation is the basis for the analogy of chemical bonding between pancake bonded radical π-dimers and other charge shift bonded molecules, such as F(2). By extending the CS bonding concept to a new class of molecules, we find a novel application of the lone pair bond weakening effect (LPBWE) in which the doubly occupied π-orbitals play the role of lone pairs.     

Oxidation of phenol in aqueous acid: characterization and reactions of radical cations vis-à-vis the phenoxyl radical

Aqueous sulfuric acid containing up to approximately 14 M acid (H0 > or = -7.0) was used as solvent in pulse radiolytic redox studies to characterize cationic transients of phenol (C6H5OH) and map their reactions. The primary radical yields were first measured to correlate the variation in various radical concentrations as a function of increasing acid fraction in the solvent. Compared to their respective values at pH 2, the G(Ox*) increased with almost a linear slope of approximately 0.024 micromol J(-1) for H0(-1) (or pH(-1)) up to H0 -6.0 (Ox* = *OH + SO4*-), whereas G(H*) increased with a slope of approximately 0.033 micromol J(-1) for H0(-1) (or pH(-1)) up to H0 -5.0. In the presence of > 10 M acid (H0 < -5.0), phenol was oxidized to its radical cation, C6H5OH*+, which further reacted with phenol and generated the secondary, dimeric radical cation, (C6H5OH)2*+, following an equilibrium reaction C6H5OH*+ + C6H5OH <==> (C6H5OH)2*+, with K(eq) = 315 +/- 15 M(-1). The two cationic radicals were characterized from their individual UV-vis absorption spectra and acidity. The C6H5OH*+ absorption peaks are centered at 276 and 419 nm, and it was found to be more acidic (pKa = -2.75 +/- 0.05) than (C6H5OH)2*+ (pKa = -1.98 +/- 0.02), having its major peak at 410 nm. On the other hand, in the presence of < 6.5 M acid the C6H5O* reactions followed the radical dimerization route, independent of the parent phenol concentration.     

Rate constants for cyclizations of α-hydroxy radical clocks

The 1-hydroxy-1-methyl-6,6-diphenyl-5-hexenyl radical (4a) and the 1-hydroxy-1-methyl-7,7-diphenyl-6-heptenyl radical (4b) were prepared from the corresponding PTOC esters (anhydrides of a carboxylic acid and N-hydroxypyridine-2-thione). The key step in the synthetic method for the precursors was a coupling reaction of the respective carboxylic acids with the thiohydroxamic acid, which was conducted for ca. 5 min and followed rapidly by chromatography. Rate constants for cyclizations of radicals 4a and 4b in acetonitrile and in THF were measured directly between -30 and 60 °C by laser flash photolysis methods. The Arrhenius functions in acetonitrile are log k = 9.9-2.6/2.303RT and log k = 8.9-4.4/2.303RT (kcal mol(-1)) for 4a and 4b, respectively. Rate constants for cyclizations at room temperature of 9 × 10(7) s(-1) and 4 × 10(5) s(-1) are somewhat larger than the rate constants for cyclizations of analogous alkyl radicals. Crude rate constants at room temperature for H-atom trapping of 4a by thiophenol and 4b by t-butylthiol were k(T) = 1.2 × 10(9) M(-1) s(-1) and k(T) = 2 × 10(7) M(-1) s(-1), respectively, which are modestly larger than rate constants for reactions of alkyl radicals with the same trapping agents.     

Does the HO2 radical react with ketones?

The possible reactions of HO₂ with five ketones were studied using a flow tube reactor equipped with a laser magnetic resonance detector. We did not observe reactive loss of HO₂ in any of the five reactions. We place upper limits of <8 × 10⁻¹⁶, <7 × 10⁻¹⁶, <5 × 10⁻¹⁶, <4 × 10⁻¹⁶, and <9 × 10⁻¹⁶ (in units of cm³; molecule⁻¹ S⁻¹) at 298 K for the reactions of HO₂ with CH₃COCH₃, CH₃COC₂H₅, CH₃COC₃H₇, C₂H₅COC₂H₅, and CH₃COC₄H₉, respectively, to give products other than an adduct. We conclude that their reactions with HO₂ are unlikely to be important loss processes for ketones in the atmosphere. © 2000 John Wiley & Sons, Inc. Int J Chem Kinet 32: 573–580, 2000     

Sulfanyl radical addition–cyclization and its synthetic application

This review summarizes a new efficient carbon–carbon bond-forming reaction based on sulfanyl radical addition–cyclization, which proceeds by the formation of a carbon-centered radical species generated by the addition of a sulfanyl radical to a multiple bond and then intramolecular addition of the resulting carbon-centered radical to a multiple bond. The synthetic potentiality was demonstrated by the syntheses of anantine, oxo-parabenzlactone, cispentacin, vitamin D, and α-kainic acid.     

A prototype hybrid 7π quinone-fused 1,3,2-dithiazolyl radical

Reaction of 1,4-naphthoquinone and SNSMF(6) (M = As, Sb) in SO(2) solution in a 1 : 2 molar ratio led to the naphthoquinone fused 1,3,2-dithiazolylium salts, 3MF(6) quantitatively by multinuclear NMR (87% isolated yield of 3SbF(6)) via the cycloaddition and oxidative dehydrogenation chemistry of SNS(+) with formation of NH(4)SbF(6) and S(8). The product 3SbF(6) was fully characterized by IR, Raman, multinuclear {(1)H, (13)C, (14)N} NMR, elemental analysis, cyclic voltammetry and single crystal X-ray crystallography. The reduction of 3SbF(6) with ferrocene (Cp(2)Fe) in refluxing acetonitrile (CH(3)CN) led to the first isolation of a fused quinone-thiazyl radical, 3˙ in 73% yield. The prototype hybrid quinone-thiazyl radical 3˙ was fully characterized by IR, Raman microscopy, EI-MS, elemental analysis, solution and solid state EPR, magnetic susceptibility (2-370 K) and was found to form π*-π* dimers in the solid state as determined by single crystal X-ray crystallography. Furthermore, the thermal decomposition of 3˙ led to a novel quinone-fused 1,2,3,4-tetrathiine, 10 (x = 2) and the known 1,2,5-thiadiazole, 11. The energetics of the cycloadditon and oxidative dehydrogenation chemistry of SNS(+) and 1,4-naphthoquinone leading to 3SbF(6) were estimated in the gas phase and SO(2) solution by DFT calculations (PBE0/6-311G(d)) and lattice enthalpies obtained by the volume based thermodynamic (VBT) approach in the solid state. The gas phase ion energetics (ionization potential (IP) and electron affinity (EA)) of 3˙ are compared to related 1,3,2- and 1,2,3-dithiazolyl radicals.     

Simulation and analysis of free radical branching copolymerization kinetics

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Kinetics of the radical scavenging activity of β-carotene-related compounds

To clarify the non-enzymatic radical-scavenging activity of β-carotene-related compounds and other polyenes, we used differential scanning calorimetry to study the kinetics of radical polymerization of methyl methacrylate (MMA) by 2,2′-azobisisobutyronitrile (AIBN) or benzoyl peroxide (BPO) in the absence or presence of polyenes under nearly anaerobic conditions at 70°C, and analyzed the results with an SAR approach. The polyenes studied were all-trans retinol, retinol palmitate, calciferol, β-carotene and lycopene. Polyenes produced a small induction period. The stoichiometric factor (n) (i.e. the number of radicals trapped by each inhibitor molecule) of polyenes was close to 0. Tetraterpenes (β-carotene, lycopene) suppressed significantly more of the initial rate of polymerization (R ^inh) than did diterpenes (retinol, retinol palmitate). The inhibition rate constants (k ^inh) for the reaction of β-carotene with AIBN-or BPO-derived radicals were determined to be 1.2–1.6?×?10⁵ l?/?mol?s, similar to published values. A linear relationship between k ^inh and the kinetic chain length (KCL) for polyenes was observed; as k ^inh increased, KCL decreased. KCL also decreased significantly as the number of conjugated double bonds in the polyenes increased. Polyenes, particularly β-carotene and lycopene, acted as interceptors of growing poly-MMA radicals.     

Is the 1,3,5-tridehydrobenzene triradical a cyclopropenyl radical analogue?

The gas-phase heat of formation (DeltaH(f,298)) of the 1,3,5-tridehydrobenzene triradical has been determined by using a negative ion thermochemical cycle. The first three measurements carried out were of the gas-phase acidity of 3,5-dichlorobenzoic acid, the enthalpy for decarboxylation of 3,5-dichlorobenzoate, and the enthalpy for chloride loss from 3,5,-dichlorophenide and constitute the measurement of the heat of formation for 5-chloro-m-benzyne. The last two measurements, the electron affinity of 5-chloro-m-benzyne, and the threshold for chloride loss from 5-chloro-m-benzyne, when combined with DeltaH(f,298) of 5-chloro-m-benzyne, give the heat of formation of the triradical. The 5-chloro-m-benzyne heat of formation is 116.2 +/- 3.7 kcal/mol. The heat of formation of the 1,3,5-tridehydrobenzene triradical measured in this work is 179.1 +/- 4.6 kcal/mol. This heat of formation was used to derive the bond dissociation energy (BDE) at the 5-position of m-benzyne, a third BDE in benzene. The BDE, at 109.2 +/- 5.6 kcal/mol, is ca. 4 kcal/mol lower than the first BDE in benzene (112.9 kcal/mol) and significantly higher than the BDE of phenyl radical at the meta position. The agreement between the first and third BDEs implies that the triradical is best described as a phenyl radical that interacts little with a m-benzyne moiety. The experimentally measured BDE is in good agreement with multireference configuration interaction calculations, which predict a (2)A(1) ground state for the Jahn-Teller distorted triradical. The trends in the first, second, and third BDEs of benzene are similar to those found for cyclopropane, suggesting a cyclopropenyl-like electronic structure within the six-membered ring of the 1,3,5-benzene triradical.     

Is the HCCS radical linear in the excited state?

The A (2)Pi-X (2)Pi 415 nm band system of the linear HCCS radical has been known since 1978, but the vibronic structure in this complex spectrum, which has both spin-orbit and Renner-Teller complications, has never been satisfactorily assigned, despite serious experimental and theoretical efforts. In a further attempt to understand the spectrum, we have studied the laser-induced fluorescence spectra of jet-cooled HCCS and DCCS, produced from thiophene precursors using the discharge jet technique. The 0(0) (0) bands of HCCS and DCCS have been rotationally analyzed, providing precise ground and excited state spin-orbit splittings. The energy levels of the v(')=0 (2)Pi(3/2) component of DCCS are found to be perturbed by a very low-lying (2)Sigma vibronic level, indicating that the HCC bending mode Renner-Teller effect is much larger than predicted by ab initio calculations with a linear excited state geometry. With this observation, the vibronic bands in the spectra of both isotopomers have been consistently assigned for the first time. Model calculations show that the large Renner-Teller effect and substantially different HCCS and DCCS excited state zero-point spin-orbit splittings can be explained with the assumption of a quasilinear excited state geometry.     

Controlled radical copolymerization of N-vinylpyrrolidone with 1,1,1,3,3,3-hexafluoroisopropyl-α-fluoroacrylate

Narrow disperse copolymers of N-vinylpyrrolidone with 1,1,1,3,3,3-hexafluoroisopropyl-α-fluoroacrylate have been prepared for the first time by reversible addition fragmentation chain transfer pseudo-living radical polymerization in the presence of benzyl dithiobenzoate. The relative activities of the monomers indicating the occurrence of alternating copolymerization have been estimated. The copolymerization of equimolar N-vinylpyrrolidone-1,1,1,3,3,3-hexafluoroisopropyl-α-fluoroacrylate mixtures shows typical features of reversible addition fragmentation chain transfer pseudoliving radical polymerization: deceleration of polymerization compared to the classical radical process, degeneration of the gel effect, successive increase in the number-average molecular mass with conversion, and formation of narrow disperse copolymers.     

Does metal ion complexation make radical clocks run fast?

Ab initio molecular orbital and density functional calculations at the CBS-RAD(QCISD,B3-LYP) level for Li+ and at B3LYP for Na+, K+, Cu+,and Ag+ reveal that the barrier to ring-closure of the 1-hexen-6-yl ("Delta(5)-hexenyl") radical to the cyclopentylmethyl radical, a so-called radical clock reaction, is decreased very significantly by complexation of the double bond to metal cations. This barrier lowering should occur on complexation with many metal ions, as shown by calculations on all of the monovalent ions listed above. Additional density functional calculations including explicit solvation of the model system complexed to the lithium ion with tetrahydrofuran suggest that the effect found is not limited to the gas phase but may also be significant in experimental radical clock reactions in solution, even for lithium.