Molecule‐Induced Peroxide Homolysis

The homolytic cleavage of peroxide bonds, leading to the formation of free radicals, plays an important role in the (spontaneous) oxidation of a wide variety of hydrocarbons in the presence of oxygen. Such aerobic oxidations can be desired (e.g. for industrially applied autoxidations) or undesired (e.g. food deterioration). In this contribution we provide experimental and computational evidence for a molecule‐induced homolytic dissociation mechanism between alkyl peroxide and compounds featuring weakly bonded H atoms such as (di)unsaturated hydrocarbons.     

A density functional study of O-O bond cleavage for a biomimetic non-heme iron complex demonstrating an Fe(v)-intermediate

Density functional theory using the B3LYP hybrid functional has been employed to investigate the reactivity of Fe(TPA) complexes (TPA = tris(2-pyridylmethyl)amine), which are known to catalyze stereospecific hydrocarbon oxidation when H(2)O(2) is used as oxidant. The reaction pathway leading to O-O bond heterolysis in the active catalytic species Fe(III)(TPA)-OOH has been explored, and it is shown that a high-valent iron-oxo intermediate is formed, where an Fe(V) oxidation state is attained, in agreement with previous suggestions based on experiments. In contrast to the analogous intermediate [(Por.)Fe(IV)=O](+1) in P450, the TPA ligand is not oxidized, and the electrons are extracted almost exclusively from the mononuclear iron center. The corresponding homolytic O-O bond cleavage, yielding the two oxidants Fe(IV)=O and the OH. radical, has also been considered, and it is shown that this pathway is inaccessible in the hydrocarbon oxidation reaction with Fe(TPA) and hydrogen peroxide. Investigations have also been performed for the O-O cleavage in the Fe(III)(TPA)-alkylperoxide species. In this case, the barrier for O-O homolysis is found to be slightly lower, leading to loss of stereospecificity and supporting the experimental conclusion that this is the preferred pathway for alkylperoxide oxidants. The difference between hydroperoxide and alkylperoxide as oxidant derives from the higher O-O bond strength for hydrogen peroxide (by 8.0 kcal/mol).     

Heterolytic cleavage of peroxide by a diferrous compound generates metal-based intermediates identical to those observed with reactions utilizing oxygen-atom-donor molecules

Under cryogenic stopped-flow conditions, addition of 2-methyl-1-phenylprop-2-yl hydroperoxide (MPPH) to the diiron(II) compound, [Fe(2)(H(2)Hbamb)(2)(NMeIm)(2)] (1; NMeIm=N-methylimidazole; H(4)HBamb: 2,3-bis(2-hydroxybenzamido)dimethylbutane) results in heterolytic peroxide O-O bond cleavage, forming a high-valent species, 2. The UV/Vis spectrum of 2 and its kinetic behavior suggest parallel reactivity to that seen in the reaction of 1 with oxygen-atom-donor (OAD) molecules, which has been reported previously. Like the interaction with OAD molecules, the reaction of 1 with MPPH proceeds through a three step process, assigned to oxygen-atom transfer to the iron center to form a high-valent intermediate (2), ligand rearrangement of the metal complex, and, finally, decay to a diferric mu-oxo compound. Careful examination of the order of the reaction with MPPH reveals saturation behavior. This, coupled with the anomalous non-Arrhenius behavior of the first step of the reaction, indicates that there is a preequilibrium peroxide binding step prior to O-O bond cleavage. At higher temperatures, the addition of the base, proton sponge, results in a marked decrease in the rate of O-O bond cleavage to form 2; this is assigned as a peroxide deprotonation effect, indicating that the presence of protons is an important factor in the heterolytic cleavage of peroxide. This phenomenon has been observed in other iron-containing enzymes, the catalytic cycles of which include peroxide O-O bond cleavage.     

Regioselective alkene carbon-carbon bond cleavage to aldehydes and chemoselective alcohol oxidation of allylic alcohols with hydrogen peroxide catalyzed by [cis-Ru(II)(dmp)2(H2O)2]2+ (dmp = 2,9-dimethylphenanthroline)

[reaction: see text] [cis-Ru(II)(dmp)2(H2O)2]2+ (dmp = 2,9-dimethylphenanthroline) was found to be a selective oxidation catalyst using hydrogen peroxide as oxidant. Thus, primary alkenes were very efficiently oxidized via direct carbon-carbon bond cleavage to the corresponding aldehydes as an alternative to ozonolysis. Secondary alkenes were much less reactive, leading to regioselective oxidation of substrates such as 4-vinylcyclohexene and 7-methyl-1,6-octadiene at the terminal position. Primary allylic alcohols were chemoselectively oxidized to the corresponding allylic aldehydes, e.g., geraniol to citral.     

Does the decomposition of peroxydicarbonates and diacyl peroxides proceed in a stepwise or concerted pathway?

M?ller-Plesset perturbation theory and density functional theory calculations are used to study decomposition mechanisms of polymerization initiators, such as diethyl peroxydicarbonate, trifluoroacetyl peroxide, and acetyl peroxide, which possess a general structure of RC(O)OO(O)CR. It is found that the decomposition of initiators with electron-donating R groups follows two favorable stepwise pathways: a two-bond cleavage mechanism in which the O-O single bond and one of R-C bonds of [R-C(O)O-O(O)C-R] break simultaneously followed by decomposition of the R-C(O)O(*) radical and a one-bond cleavage mechanism in which the single O-O bond cleavage produces a carboxyl radical pair and a subsequent decomposition of the carboxyl radicals. It is also found that the initiators with electron-withdrawing R groups follow the two-bond cleavage pathway only. Geometrical and energetic analyses indicate that despite the similar structures of the peroxydicarbonates, quite different decomposition energy barriers are determined by the nature of the R groups.     

Transition metal-catalyzed carbon-carbon bond activation

This tutorial review deals with recent developments in the activation of C-C bonds in organic molecules that have been catalyzed by transition metal complexes. Many chemists have devised a variety of strategies for C-C bond activation and significant progress has been made in this field over the past few decades. However, there remain only a few examples of the catalytic activation of C-C bonds, in spite of the potential use in organic synthesis, and most of the previously published reviews have dwelt mainly on the stoichiometric reactions. Consequently, this review will focus mainly on the catalytic reaction of C-C bond cleavage by homogeneous transition metal catalysts. The contents include cleavage of C-C bonds in strained and unstrained molecules, and cleavage of multiple C-C bonds such as C[triple bond]C triple bonds in alkynes. Multiple bond metathesis and heterogeneous systems are beyond the scope of this review, though they are also fascinating areas of C-C bond activation. In this review, the strategies and tactics for C-C bond activation will be explained.     

Peroxide electroreduction on bi-modified Au surfaces: vibrational spectroscopy and density functional calculations

The mechanism of the electroreduction of peroxide on Bi-submonolayer-modified Au(111) surfaces is examined using surface-enhanced Raman scattering (SERS) measurements along with detailed density functional theory (DFT) calculations. The spectroscopy shows the presence of Bi-OH and Bi-O species at potentials just positive of that where peroxide is reduced. These species are not present in solutions absent either peroxide or Bi. DFT calculations show that peroxide is unstable relative to Bi-OH when Bi is present in the (2 x 2) configuration on Au(111) known from previous work to be catalytically active. The spacing between Bi adatoms is such that peroxide association with two Bi cannot occur without O-O bond cleavage. The full Bi monolayer is catalytically inactive and exhibits none of the Bi-OH or Bi-O signals seen for the active surface. The calculations show that as the Bi coverage becomes greater and the Bi adatom spacing becomes smaller, peroxide can adsorb on Bi without O-O bond rupture. These results indicate an important role for M-OH species in peroxide electroreduction.     

Reductive lithiation of 1,3-dimethyl-2-arylimidazolidines

Naphthalene catalyzed lithiation of 1,3-dimethyl-2-phenylimidazolidine led to cleavage of the benzylic carbon-nitrogen bond, with formation of an intermediate dianion. Under similar conditions, 1,3-dimethyl-2-(4-chlorophenyl)imidazolidine underwent regioselective cleavage of the aromatic carbon-chlorine bond, leading to a 4-formylphenyllithium equivalent, whilst 1,3-dimethyl-2-(4-methoxymethylphenyl)imidazolidine underwent regioselective cleavage of the benzylic carbon-oxygen bond, leading to a 4-formylbenzyllithium equivalent.     

Intermediacy of Proton-Bound Dimers and Ion/Dipole Complexes in the Unimolecular Decompositions of Dialkyl-Peroxide Radical Cations: Evidence for a coupled proton and hydrogen-atom transfer

The unimolecular fragmentation reactions of the radical cations of diethyl, diisopropyl, dipropyl, isopropyl propyl, and di(tert-butyl) peroxide have been investigated by mass spectrometric and isotopic labeling techniques. Two competing pathways for unimolecular decomposition in the μs time regime (metastable ions) are observed: i) A combination of an α-C? C bond cleavage and a H migration gives rise to proton-bound dimers of two ketone or aldehyde molecules. ii) Ion/dipole complexes of alkyl cations and alkylperoxy radicals are generated by C–O bond cleavage. These complexes either exhibit direct losses of alkylperoxy radicals, or they rearrange via a coupled proton and H-atom transfer, this sequence of unprecedented isomerizations is completed by losses of alkyl radicals. Collisional activation experiments confirm that the ionic products of the latter process correspond to RR′C?OOH⁺; these ions can be regarded as protonated carbonyl oxides. In addition, we observe the elimination of alkenes leading to hydroperoxide radical cations and the expulsion of HO radicals. The latter process implies a C? C bond formation step between the two alkyl fragments leading to higher alkyl cations.     

Acid-catalyzed decomposition of an α-keto diazo endoperoxide

Two different decomposition modes of α-keto diazo endoperoxide $\text{1}$ are described. One is the Brønsted acid-catalyzed elimination of the diazo group leading to rearranged peroxides $\text{2}$. Deuterium labeling clearly shows the path of the rearrangement. The other reaction is a catalyzed cleavage of the peroxide bond to form diazoketone $\text{3}$.     

Photochemical reactions. 146th communication. Photochemistry of conjugated methano-epoxydienes: Participation of the neighboring cyclopropane ring in product formation via carbonyl ylide and carbene intermediates

On singlet excitation (λ = 254 nm, THF, pentane or hexane), the diastereoisomeric methano-epoxydienes (E)- 6 and (E)- 7 undergo interconversion and yield the products 8 – 11 . The main process is the cleavage of the oxirane ring to the vinyl carbene intermediate e which undergoes addition to the adjacent double bond furnishing the cyclopropene 8 . The alternative carbene intermediate f is evidenced by the formation of the cyclobutene 10 . For the fragmentation leading to 11 , the carbene f as well as the dipolar species h are considered as possible intermediates. On triplet sensitization (acetone, λ > 280 nm), (E)- 7 shows behavior typical of epoxydienes, undergoing fission of the C? O bond of the oxirane ring and isomerization to the compounds 13 , 14 and (E/Z)- 15 .     

Activating a Peroxo Ligand for C−O Bond Formation

Dioxygen activation for effective C?O bond formation in the coordination sphere of a metal is a long‐standing challenge in chemistry for which the design of catalysts for oxygenations is slowed down by the complicated, and sometimes poorly understood, mechanistic panorama. In this context, olefin–peroxide complexes could be valuable models for the study of such reactions. Herein, we showcase the isolation of rare “Ir(cod)(peroxide)” complexes (cod=1,5‐cyclooctadiene) from reactions with oxygen, and then the activation of the peroxide ligand for O?O bond cleavage and C?O bond formation by transfer of a hydrogen atom through proton transfer/electron transfer reactions to give 2‐iradaoxetane complexes and water. 2,4,6‐Trimethylphenol, 1,4‐hydroquinone, and 1,4‐cyclohexadiene were used as hydrogen atom donors. These reactions can be key steps in the oxy‐functionalization of olefins with oxygen, and they constitute a novel mechanistic pathway for iridium, whose full reaction profile is supported by DFT calculations.     

STRUCTURAL CRITERIA FOR CHEMILUMINESCENCE IN ACYL PEROXIDE DECOMPOSITION REACTIONS

Abstract— A group of new moderately bright chemiluminescent reactions is reported involving decomposition of certain acyl peroxide derivatives. The new chemilurninescent reactions are compared to other acyl peroxide decompositions which are not strongly chemiluminescent (Chart I). The results are interpreted in terms of a concerted multiple bond cleavage peroxide decomposition mechanism, where the simultaneous formation of at least two stable molecules is suggested to be the source of the substantial energy required for the formation of an excited reaction product in chernilurninescence.     

Kinetic studies on thermal decomposition of polystyrene peroxide

Polystyrene peroxide has been synthesized and its decomposition has been studied by thermogravimetry and differential thermal analysis. Polystyrene peroxide has been found to decompose exothermically at about 110°C. The activation energy for the decomposition was estimated to be 30 kcal/mole both by the Jacobs and Kureishy method and by fitting the α versus time curves to the first-order kinetic equation. This suggests that the rate-controlling step in the decomposition of polystyrene peroxide is cleavage of the OO bond.     

A quantum chemical study of the mechanism of manganese catalase

The catalytic mechanism of manganese catalase has been studied using the Becke's three parameter hybrid method with the Lee, Yang and Parr correlation functional. On the basis of available experimental information on the geometric and electronic structure of the active manganese dimer complex, different possibilities were investigated. The mechanism finally suggested consists of eight steps. In the first steps, the first hydrogen peroxide becomes bound and its O–O bond is activated. This occurs in a spin-forbidden process found to be common in many biological processes where the O–O bond is cleaved, and two general rules are formulated for the requirements for a low activation energy in this type of reaction. As the O–O bond is cleaved a hydroxyl radical is initially formed in the overall rate-limiting step of the catalytic cycle. This radical is then immediately and irreversibly quenched in a strongly exothermic step. In the subsequent steps, the second hydrogen peroxide becomes bound and its two O–H bonds are broken, leading to the formation of an O₂ molecule, which is released. Parallels between the reversal of the present O–O cleavage mechanism in manganese catalase and the recently suggested O–O bond formation in photosystem II are drawn. Received: 12 July 2000 / Accepted: 12 July 2000 / Published online: 21 December 2000     

Dioxetanones’ peroxide bond as a charge-shifted bond: implications in the chemiluminescence process

Six dioxetanone molecules, ranging in complexity from simple dioxetanone to firefly dioxetanone, were studied by performing M06/6-311G(d,p) calculations. The quantum theory of atoms in molecules and the electron localization function was applied to analyze the peroxide and carbon–carbon bonds of the dioxetanone ring. Both approaches demonstrated that the peroxide bond is not covalent, but charge-shifted. This means that for this bond the covalent “electron sharing” is relatively unimportant, and it is the stabilizing resonance energy that causes the bonding. For the contrary, the carbon–carbon bond is covalent. These discoveries indicate that no biradical species should be formed in the dioxetanone decomposition, and that the most probable rate-determining step should be the carbon–carbon cleavage.     

Computational study on nonenzymatic peptide bond cleavage at asparagine and aspartic acid

Nonenzymatic peptide bond cleavage at asparagine (Asn) and glutamine (Gln) residues has been observed during peptide deamidation experiments; cleavage has also been reported at aspartic acid (Asp) and glutamic acid (Glu) residues. Although peptide backbone cleavage at Asn is known to be slower than deamidation, fragmentation products are often observed during peptide deamidation experiments. In this study, mechanisms leading to the cleavage of the carboxyl-side peptide bond of Asn and Asp residues were investigated using computational methods (B3LYP/6-31+G**). Single-point solvent calculations at the B3LYP/6-31++G** level were carried out in water, utilizing the integral equation formalism-polarizable continuum (IEF-PCM) model. Mechanism and energetics of peptide fragmentation at Asn were comparatively analyzed with previous calculations on deamidation of Asn. When deamidation proceeds through direct hydrolysis of the Asn side chain or through cyclic imide formationvia a tautomerization routeit exhibits lower activation barriers than peptide bond cleavage at Asn. The fundamental distinction between the mechanisms leading to deamidationvia a succinimideand backbone cleavage was found to be the difference in nucleophilic entities involved in the cyclization process (backbone versus side-chain amide nitrogen). If deamidation is prevented by protein three-dimensional structure, cleavage may become a competing pathway. Fragmentation of the peptide backbone at Asp was also computationally studied to understand the likelihood of Asn deamidation preceding backbone cleavage. The activation barrier for backbone cleavage at Asp residues is much lower (approximately 10 kcal/mol) than that at Asn. This suggests that peptide bond cleavage at Asn residues is more likely to take place after it has deamidated into Asp.     

Phosphodiester and N-glycosidic bond cleavage in DNA induced by 4-15 eV electrons

Thin molecular films of the short single strand of DNA, GCAT, were bombarded under vacuum by electrons with energies between 4 and 15 eV. Ex vacuo analysis by high-pressure liquid chromatography of the samples exposed to the electron beam revealed the formation of a multitude of products. Among these, 12 fragments of GCAT were identified by comparison with reference compounds and their yields were measured as a function of electron energy. For all energies, scission of the backbone gave nonmodified fragments containing a terminal phosphate, with negligible amounts of fragments without the phosphate group. This indicates that phosphodiester bond cleavage by 4-15 eV electrons involves cleavage of the C-O bond rather than the P-O bond. The yield functions exhibit maxima at 6 and 10-12 eV, which are interpreted as due to the formation of transient anions leading to fragmentation. Below 15 eV, these resonances dominate bond dissociation processes. All four nonmodified bases are released from the tetramer, by cleavage of the N-glycosidic bond, which occurs principally via the formation of core-excited resonances located around 6 and 10 eV. The formation of the other nonmodified products leading to cleavage of the phosphodiester bond is suggested to occur principally via two different mechanisms: (1) the formation of a core-excited resonance on the phosphate unit followed by dissociation of the transient anion and (2) dissociation of the CO bond of the phosphate group formed by resonance electron transfer from the bases. In each case, phosphodiester bond cleavage leads chiefly to the formation of stable phosphate anions and sugar radicals with minimal amounts of alkoxyl anions and phosphoryl radicals.     

Chromium(VI) based oxidants-1 : Chromium peroxide complexes as versatile,mild, and efficient oxidants in organic synthesis

The preparation of 2,2'-bipyridylchromium peroxide, pyridinechromium peroxide, and chromium peroxide etherate is described. 2,2'-Bipyridylchromium peroxide converts different classes of alcohols to the carbonyl compounds. In 1,2-diols C—C bond cleavage occurs extensively. α-Hydroxy acids are decarboxylated quantitatively. Oximes are converted to their carbonyl compounds and thiols to their disulfides, dihydroxy phenolic compounds to quinones, benzyl amine to benzaldehyde, aromatic amines to their azo compounds, anthracene and phenanthrene to their quinones. Pyridinechromium peroxide converts different classes of alcohols efficiently to the carbonyl compounds, thiols to their disulfides, anthracene to anthraquinone. Mandelic and benzilic acids are decarboxylated very efficiently. Chromium peroxide etherate is an efficient reagent for the oxidation of different classes of alcohols to their carbonyl compounds.     

Understanding selectivity in the oxidative addition of the carbon-sulfur bonds of 2-cyanothiophene to Pt(0)

The reaction of 2-cyanothiophene with a zerovalent platinum bisalkylphosphine fragment yields two thiaplatinacycles derived from the cleavage of the substituted and unsubstituted C-S bonds. While cleavage away from the cyano group is preferred kinetically, cleavage adjacent to the cyano group is preferred thermodynamically. Density functional theory using B3LYP level of theory on a model of this system is consistent with experimental results in that the transition state energy leading to the formation of the kinetically favored C-S bond cleavage product is lower by 5.3 kcal mol(-1) than the barrier leading to the thermodynamically favored product. There is a 6.7 kcal mol(-1) difference between these two products. The cyano substituent at the 2- position of thiophene did not substantially change the mechanism involved in the C-S bond cleavage of thiophene previously reported.