Showing papers on "Homolysis published in 1988"

Transition-metal-centered radicals in organic synthesis. Titanium(III)-induced cyclization of epoxy olefins

Abstract: We wish to report a solution to this problem which allows the direct synthesis of functionalized cyclopentane derivatives. This new reaction is based on an analogy to the extremely facile rearrangement of cyclopropylmethyl radical to homoallyl radical (eq 2). A a-complex of an epoxide with a paramagnetic transition metal4 having a half-filled (*-symmetry) d orbital represents an electronic analogue of the cyclopropylmethyl moiety. By analogy to eq 2, release of ring strain might be expected to drive the homolytic C-0 bond cleavage in eq 3.

Bond dissociation energies for common organic compounds

Abstract: Homolytic bond dissociation energies are calculated for a wide variety of organic compounds. The values reflect the latest experimental data on the heats of formation of simple alkyl radicals.

An ab initio quantum chemical investigation on the effect of the magnitude of the T-O-T angle on the Broensted acid characteristics of zeolites

Abstract: Ab initio molecular orbital calculations are used to monitor the effect of increasing SiOAl angle (SiOAl) on the acidic properties of bridged hydroxyl groups in zeolites A 3-21G basis set is employed in the calculations, and the bridged hydroxyl group is modeled via an aluminosiloxane unit Increasing angle SiOAl is shown to give rise to decrease in the stretching frequency of the OH group (anti v/sub OH/) with a corresponding decrease in the ionicity of the OH bond The decrease in ionicity of the OH bond indicates that increasing angle SiOAl gives rise to a decrease in acidity The decreased strength of the OH bond as evidenced by the decreased anti v/sub OH/ value suggests that the OH bond is unstable when situated at a high angle SiOAl link with the decreased polarity of the bond tending to favor homolytic dissociation over heterolytic dissociation It is also shown that angle SiOH exhibits decreased flexibility with increasing angle SiOAl, suggesting that the SiOH bending frequency should be greater for zeolites with higher TOT angles

The methyl(cyclam)nickel(III) dication in aqueous solutions: determination of the equilibrium constant of homolysis, kinetics of oxygen insertion, and methyl transfer to aquated chromium(2+)

Abstract: Le compose du titre est prepare par reaction du radical methyle avec le complexe LNi 2+ (L=cyclam=tetraaza-1,4,8,11cyclotetradecane)

Catalytic-site mapping of pyruvate formate lyase. Hypophosphite reaction on the acetyl-enzyme intermediate affords carbon-phosphorus bond synthesis (1-hydroxyethylphosphonate).

Abstract: Pyruvate formate-lyase of Escherichia coli cells, a homodimeric protein of 2 x 85 kDa, is distinguished by the property of containing a stable organic free radical (g = 2.0037) in its resting state. The enzyme (E-SH) achieves pyruvate conversion to acetyl-CoA via two distinct half-reactions (E-SH + pyruvate in equilibrium E-S-acetyl + formate; E-S-acetyl + CoA in equilibrium E-SH + acetyl-CoA), the first of which has been proposed to involve reversible homolytic carbon-carbon bond cleavage [J. Knappe et al. (1984) Proc. Natl Acad. Sci. USA 81, 1332-1335]. Present studies identified Cys-419 as the covalent-catalytic cysteinyl residue via CNBr fragmentation of E-S-[14C]acetyl and radio-sequencing of the isolated peptide CB-Ac (amino acid residues 406-423). Reaction of the formate analogue hypophosphite with E-S-acetyl was investigated and found to produce 1-hydroxyethylphosphonate with a thioester linkage to the adjacent Cys-418. The structure was determined from the chymotryptic peptide CH-P (amino acid residues 415-425), using 31P-NMR spectroscopy (delta = 44 ppm) and by chemical characterisation through degradation into 1-hydroxyethylphosphonate with phosphodiesterase or bromine. This novel P-C-bond synthesis involves the enzyme-based free radical and is proposed to resemble the physiological C-C-bond synthesis (pyruvate production) from formate and E-S-acetyl. These findings are interpreted as proof of a radical mechanism for the action of pyruvate formate-lyase. The central Cys-418/Cys-419 pair of the active site shows a distinctive thiolate property even in the inactive (nonradical) form of the enzyme, as determined using an iodoacetate probe.

Homolytic reactions of ligated boranes. Part 9. Overall addition of alkanes to electron-deficient alkenes by a radical chain mechanism

Abstract: Methyl bromoacetate and ethyl 2-bromopropanoate are reduced by Bun3P→BH3 or Bun3P→BH2Ph to methyl acetate and ethyl proponoate, respectively, in chlorobenzene at 80–110 °C in the presence of dibenzoyl peroxide or t-butyl perbenzoate. Amine complexes of borane or phenylborane are much less effective reducing agents. The reductions may also be initiated photochemically and are inhibited by a phenolic radical scavenger. A homolytic chain mechanism is proposed in which the phosphine–boryl radical abstracts halogen from the bromo ester and is subsequently regenerated by reaction of an α-(alkoxycarbonyl) alkyl radical with the phosphine–borane. The latter propagation step, together with halogen abstraction from Rl and addition of the derived alkyl radical to the CC bond, is also involved in the chain reaction between Bun3P→BH2Ph, an alkyl iodide, and ethyl acrylate according to equation (A); Bun3P→BH3 reacts similarly but gives lower yields of ester. Reaction (A) proceeds smoothly at 110 °C Bun3P→BH2Ph + Rl + CH2CHCO2Et→RCH2CH2CO2Et + Bun3P→BHIPh (A) when initiated by t-butyl perbenzoate and moderate yields of isolated esters were obtained from n-butyl iodide, cyclohexyl iodide, and 3β-iodocholest-5-ene. This last iodide gives an epimeric mixture of 3α-and 3β-esters in total isolated yield of ca. 50%. Similar addition reactions take place between Bun3P→BH2Ph, Bunl, and diethyl vinylphosphonate or phenyl vinyl sulphone. It is concluded that Bun3P→BH3 and particularly Bun3P→BH2Ph offer promise as alternatives to tin, mercury, and germanium hydrides in radical chain reactions of synthetic value.

4-alkyl radical extrusion in the cytochrome P-450-catalyzed oxidation of 4-alkyl-1,4-dihydropyridines.

Abstract: Rat liver microsomal cytochrome P-450 oxidizes the 4-methyl, 4-ethyl (DDEP), and 4-isopropyl derivatives of 3,5-bis(carbethoxy)-2,6-dimethyl-1,4-dihydropyridine to mixtures of the corresponding 4-alkyl and 4-dealkyl pyridines. A fraction of the total microsomal enzyme is destroyed in the process. The 4-dealkyl to 4-alkyl pyridine metabolite ratio, the extent of cytochrome P-450 destruction, and the rate of spin-trapped radical accumulation are correlated in a linear inverse manner with the homolytic or heterolytic bond energies of the 4-alkyl groups of the 4-alkyl-1,4-dihydropyridines. No isotope effects are observed on the pyridine metabolite ratio, the destruction of cytochrome P-450, or the formation of ethyl radicals when [4-2H]DDEP is used instead of DDEP. N-Methyl- and N-ethyl-DDEP undergo N-dealkylation rather than aromatization but N-phenyl-DDEP is oxidized to a mixture of the 4-ethyl and 4-deethyl N-phenylpyridinium metabolites. In contrast to the absence of an isotope effect in the oxidation of DDEP, the 4-deethyl to 4-ethyl N-phenylpyridinium metabolite ratio increases 6-fold when N-phenyl[4-2H]DDEP is used. The results support the hypothesis that cytochrome P-450 catalyzes the oxidation of dihydropyridines to radical cations and show that the radical cations decay to nonradical products by multiple, substituent-dependent, mechanisms.

Homolytic reactions of ligated boranes. Part 10. Electron spin resonance studies of radicals derived from ligated arylboranes

Abstract: The ligated arylboryl radicals L→ḂHAr [L = Me3N, Et3P, or (MeO)3P; Ar = Ph or p-ButC6H4] have been generated in oxirane solvent by hydrogen atom abstraction from L→BH2Ar using t-butoxyl radicals produced by u.v. photolysis of di-t-butyl peroxide. The e.s.r. spectra of the phosphine- or phosphite-ligated radicals show that there is substantial conjugative delocalisation of the unpaired electron from boron onto the aromatic rings, although this delocalisation is less extensive than in comparable benzylic carbon-centred radicals. The results of ab initio molecular orbital calculations support the proposal that hyperconjugative delocalisation onto the phosphorus ligand competes with conjugative delocalisation onto the ring in the complexed arylboryl radicals. The e.s.r. spectra of the amine–arylboryl radicals were too weak to detect, although these radicals and Et3P→ḂHAr abstract halogen atoms readily from alkyl bromides to afford spectra of the corresponding alkyl radicals. The ligated arylboryl radicals are less reactive and more selective in bromine atom abstraction than homoleptic ligated alkylboryl radicals, presumably because the former are appreciably stabilised by conjugative delocalisation of the unpaired electron onto the aromatic rings.

Energetics of metal-oxygen bonds in metal complexes of β-diketones

Abstract: The thermochemical data available for standard enthalpies of formation, both in the crystalline and gaseous phases, of metal B-diketonates is reviewed, and the calculation of enthalpies of gas-phase decomposition of these complexes is presented. The homolytic metal-oxygen bond-dissociation enthalpies for several complexes of &diketones with different metals are calculated, and the results discussed in terms of structure and bonding and, whenever appropriate, trends in the data are suggested and discussed.

Inactivation of Escherichia coli pyruvate formate-lyase by hypophosphite: evidence for a rate-limiting phosphorus-hydrogen bond cleavage.

Abstract: Recently, Knappe and co-workers [Knappe, J., Neugebauer, F. A., Blaschkowski, H. P., & Ganzler, M. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1332] have shown that the catalytically active form of pyruvate formate-lyase from Escherichia coli is associated with a protein-bound organic free radical which is quenched upon enzyme inactivation by oxygen or hypophosphite. Our interest in the chemical mechanism of this unusual enzymatic reaction has led us to investigate several key aspects of the inactivation of the lyase by hypophosphite and its relationship to the normal enzymatic reaction. We report here that the inactivation of both the free and acetylated forms of the lyase is subject to a primary kinetic isotope effect using [2H2]hypophosphite. This suggests that phosphorus-hydrogen bond cleavage is at least partially rate limiting during inactivation. In addition, the inactivated enzyme can be fully reactivated. We have also determined a Vmax/Km isotope effect of 3.6 +/- 0.7 for pyruvate formation from [2H]formate and acetyl coenzyme A. Thus, carbon-hydrogen bond cleavage is partially rate limiting in the normal reverse reaction. On the basis of our findings, the previous work of Knappe and co-workers, the likelihood that hypophosphite is a formate analogue, the known susceptibility of both hypophosphite and formate to homolysis, and a chemical precedent for homolytic cleavage of pyruvate, we offer a preliminary mechanistic proposal for the lyase reaction.

Ferric bleomycin catalyzed reduction of 10-hydroperoxy-8,12-octadecadienoic acid: evidence for homolytic O-O bond scission.

Abstract: 10-Hydroperoxy-8,12-octadecadienoic acid (1) is reduced by ferric bleomycin in aqueous and methanol solutions to yield 10-oxo-8-decenoic acid (2) as the major product (80-90%). Trace amounts of 10-oxo-8,12-octadecadienoic acid (3) (5-10%) and 10-hydroxy-8,12-octadecadienoic acid (4) (5-10%) were also detected. The reduction product ratios remained relatively constant in the presence or absence of the reducing substrate phenol, over the pH range 6.5-8.5, in incubations from 30 s to 1 h, and over a series of ferric drug concentrations. In the presence of phenol, incubations of ferric bleomycin and 1 yielded 2,2'-biphenol and 4,4'-biphenol as oxidation products. In reactions where phenol was replaced with the drug's biological substrate DNA, 1 was found to support ferric bleomycin mediated DNA degradation. Extracts from these assays also found 2 to be the major reduction product derived from the oxidant, with trace quantities of 3 and 4 present. Control experiments demonstrated the reactions to be dependent on both 1 and ferric bleomycin. The reduction products 2 and 3 have previously been shown to originate from transient alkoxyl radicals formed by homolysis of the peroxy O-O bond. Product 4 results from heterolysis of the peroxy O-O bond [Labeque, R., & Marnett, L. J. (1987) J. Am. Chem. Soc. 109, 2828-2829]. The results of this investigation indicate that ferric bleomycin catalyzes the homolytic cleavage of the O-O bond of 1 almost exclusively while supporting various oxidative reactions.

Compensation effects in the activation parameters for the homolytic dissociation of transition metal-alkyl bonds.

Abstract: Determining the activation enthalpies of the homolytic dissociation of transition metal–alkyl bonds constitutes one of the most useful methods of deducing such bond dissociation energies. For several series of organocobalt compounds it has been found that trends of increasing enthalpies of activation for homolytic cobalt–carbon bond dissociation (i.e., of cobalt–carbon bond dissociation energies) are accompanied by partially compensating trends of increasingly positive entropies of activation. Evidence is advanced that these compensation effects are genuine. A suggested explanation is that, with increasing endothermicity of the bond dissociation process, the transition state becomes more “product-like,” i.e., further along the path to dissociation.

The mechanism of adenosylcobalamin-dependent rearrangements.

Abstract: Adenosylcobalamin (AdoCbl)-dependent rearrangements are a group of reactions with no obvious precedents in organic chemistry. In every case, they are characterized by a mechanism in which a hydrogen atom on one carbon atom exchanges places with a group X on an adjacent carbon: (formula; see text) Much experimental work indicates that an AdoCbl rearrangement is initiated by homolysis of the C-Co bond of the cofactor. The migrating hydrogen is then abstracted from the substrate by the resulting 5'-deoxyadenosyl radical, or by a second radical that is generated elsewhere at the active site, and, after the migration of group X, is returned to the product in a similar reaction. In at least some of the rearrangements, group X migration may occur via a cation radical intermediate that formed by the departure of X with its electrons, a process assisted by the unpaired electron left behind on the adjacent carbon after the abstraction of the migrating hydrogen. Once C-Co bond cleavage has initiated the reaction by producing a free radical at the active site, the corrin ring plays no further role in the rearrangements.

High temperature oxidation of n-alkyl benzenes

Abstract: In a flow reactor study of the oxidation of n-butyl benzene at 1069K, the intermediate species that were observed were essentially the same as those found during oxidation studies of the other members of the homologous series: methyl, ethyl and n-propyl benzene. Furthermore, the same three types of processes responsible for the removal of the n-alkyl side chain found to be important in studies of the oxidation of the smaller n-alkyl benzenes were found to be responsible for removal of the n-butyl side chain: 1) abstraction of a hydrogen from the alkyl group, decomposition of the radical and oxidation of the subsequently formed species; 2) displacement of the alkyl group by a radical species—usually an H atom; 3) thermal cleavage (homolysis) of part of the side chain followed by oxidation of the resultant radicals. As was found in the study of the other members of the homologous series, the oxidation mechanism of the alkane analogue, in this case n-butane, provided a framework for predicting the intermediates that would be formed by the side chain removal processes. The results of this study have led to the development of a simple, general, mechanistic model for the oxidation of n-alkyl benzenes that qualitatively represents the processes responsible for the removal of n-alkyl side chains.

Pteridines. Part LXXXV. Chemical synthesis of deoxysepiapterin and 6‐acylpteridines by acyl radical substitution reactions

Abstract: A new synthesis of deoxysepiapterin (2), one of the two yellow eye pigments of the Drosophila mutant sepia, is described. The synthetic approach makes use of a homolytic nucleophilic acylation of 7-(alkylthio)pteridine derivatives (11, 13, 15, 18, 20) leading to the corresponding 6-acyl derivatives ( 21–27). Desulfurizations have been achieved for the first time in the pteridine series using Raney-Co,Raney-Cu, or CuAl alloy in alkaline medium. Besides cleavage of the C(7)S bond, further reductions of the CO group at C(6) and the C(7)N(8) bond are detected as side reactions leading to 6-(1-hydroxyalkyl) (34, 35, 42, 43) and 6-acyl-7,8-dihydro derivatives (2, 36, 37), respectively, The newly synthesized compounds have been characterized by elemental analysis, pK determination, UV and 1H-NMR spectra.

Perfluoroalkanes obtained by photochemical fluorination and use thereof as polymerization initiators

Abstract: The present invention relates to branched perfluoroalkanes which, having bonds between a quaternary carbon atom and a tertiary carbon atom, easily undergo a homolytic scission of the C-C bond thereby releasing (non-persistent) radicals which may be used as initiators of polymerization of ethylenically unsaturated monomers. A further object of the present invention are new perfluoroalkanes having at least 9 carbon atoms belonging to the above described group.

A Simple New Synthesis of Macrolides by a Four Atom Ring Expansion of Cyclic Ketones through a Consecutive Intramolecular Homolytic Addition—β-Scission of Alkoxyl Radicals. A New Entry to the Synthesis of 15-Pentadecanolide (Exaltolide)

Abstract: We describe a simple new synthesis of 16-membered macrolide, 15-pentadecanolide, based on a novel four atom ring expansion of cyclic ketones through a consecutive intramolecular homolytic addition—β-scission of alkoxyl radicals.

Properties of complexes with cobalt–carbon bonds formed by reactions of aliphatic free radicals with nitrilotriacetate–cobalt(II) in aqueous solution. A pulse radiolysis study

Abstract: The reactions of the aliphatic free radicals ˙R [˙R =˙CH3, ˙CH2OH, ˙CH(CH3)OH, ˙C(CH3)2OH, ˙CH(CH3)OC2H5, ˙CH2CO–2 and CO˙–2] with CoII(nta)(H2O)–2 in aqueous solutions yield the unstable transients (nta)CoIII—R(H2O)– with cobalt–carbon σ bonds. The complexes with ˙R =˙CH3, ˙CH2OH, ˙CH(CH3)OH, ˙C(CH3)2OH and ˙CH(CH3)OC2H5 decompose via homolytic cleavage of the cobalt–carbon bond. The kinetics of reaction of these free radicals with (nta)CoIII—R(H2O)– are reported. The only organic products of the latter reactions are the dimers R—R for ˙R =˙CH3 and ˙CH2OH, whereas a mixture of disproportionation products and dimers is formed for ˙R =˙CH(CH3)OH and ˙C(CH3)2OH. For ˙R =˙CH2OH, ˙CH(CH3)OH and ˙C(CH3)2OH the pKa values for the acidic dissociation of the alcoholic group in the complexes are reported. For ˙R =˙CH2OH the activation parameters for the homolytic dissociation of the cobalt–carbon bond and the acidic dissociation are reported. The ultraviolet–visible spectra of all the transients are reported.