Metal-mediated formation of carbon-halogen bonds

Organic halides represent basic starting materials for numerous metal-catalyzed organic transformations. Generally, the carbon-halogen is broken in the first step, that is, an oxidative addition reaction, of the catalytic cycle. On the other hand, very little is known about the reverse reaction, carbon-halogen reductive elimination from a transition-metal center. In this Concept article, we describe the examples of C(sp(3))-halide and C(sp(2))-halide reductive-elimination reactions which demonstrate that this type of reactivity can be quite common in organometallic chemistry. Although the thermodynamic driving force for the formation of carbon-halogen bonds is relatively small, the kinetic barrier for these reactions can also be low. Thus, C-halide reductive elimination can compete favorably with the more established organic transformations, such as C-C reductive elimination.     

水溶液中2,4,6-三溴苯酚在银阴极上的选择性脱卤

采用循环伏安法比较了玻碳、光亮银和粗糙化银电极对2,4,6-三溴苯酚还原脱卤反应的电催化活性, 初步研究了碱性水溶液中2,4,6-三溴苯酚在粗糙化银电极上的还原脱卤历程; 在此基础上, 利用恒电位电解法进一步探索了2,4,6-三溴苯酚在粗糙化银电极上的电还原脱卤历程. 结果表明, 粗糙化银电极对2,4,6-三溴苯酚的选择性还原脱卤反应具有优良的电催化活性, 且其活性优于光亮银和玻碳电极; 2,4,6-三溴苯酚在粗糙化银电极上的还原反应是个逐步脱卤过程, 推测得出其邻位和对位C—Br键的还原断裂所需的活化能非常接近, 而反应中间产物2,4-二溴苯酚的对位C—Br键的还原断裂所需的活化能比邻位要低; 2,4,6-三溴苯酚能实现完全脱卤生成苯酚, 主要路径为2,4,6-三溴苯酚→2,4-二溴苯酚→2-溴苯酚→苯酚.     

Halobenzenes and Ir(I): kinetic C-H oxidative addition and thermodynamic C-Hal oxidative addition

A (PNP)Ir fragment undergoes facile, room-temperature oxidative addition of C-H bonds in arenes and haloarenes in preference to aromatic carbon-halogen bonds. This preference, however, is determined to be kinetic in nature. Oxidative addition of C-Cl and C-Br is preferred thermodynamically. The products of the C-Cl or C-Br oxidative addition are separated from the C-H oxidative addition products by a high activation barrier and are only accessible at >100 degrees C. Of the C-H oxidative addition products of chlorobenzene, the isomer with the o-ClC6H4 ligand has the lowest energy.     

Relevance of electron transfer mechanism in electrocatalysis: the reduction of organic halides at silver electrodes

The mechanism of dissociative electron transfer (ET) to a series of organic chlorides has been investigated both at an inert electrode and at a catalytic surface such as Ag; electrocatalysis is important only when breaking of the carbon-halogen bond is concerted with the ET.     

Conformational analysis of dimethyl(bromomethyl)- and dimethyl(iodomethyl)phosphine oxides

Conclusions The oxides of dimethyl(bromomethyl)- and dimethyl(iodomethyl)phosphines exist as equilibrium mixtures of conformer pairs in solution, the form predominating in nonpolar solvents being that in which the phosphoryl and carbon-halogen bonds are in trans orientation.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1292–1296, June, 1981.     

Electrochemical preparation of α,α′-dicarbonylselenides

A facile preparation of α,α′-dicarbonylselenides has been performed by reaction of α-carbonyl selenocyanates with an enolate, electrogenerated by reduction of a carbon-halogen bond.     

Synthesis of charged phenyl radicals and biradicals by laser photolysis in a Fourier-transform ion cyclotron resonance mass spectrometer

The feasibility of generating substituted phenyl radicals and biradicals (with a charged substituent) in the gas phase by laser photolysis was examined by using a Fourier-transform ion cyclotron resonance mass spectrometer. The precursors were generated by ipso-substitution of a halogen atom in the radical cation of a di- or trihalobenzene by various nucleophiles. Photolytic cleavage of the remaining carbon-halogen bond(s) with 266-nm radiation was found to produce many substituted phenyl radicals in greater yields than the earlier employed method, sustained off-resonance irradiated collision-activated dissociation (SORI-CAD). Furthermore, ion generation by photolysis leads to isomerization less often than collisional activation. Finally, not only phenyl-bromine and phenyl-iodine but also certain phenyl-chlorine bonds can be cleaved by photolysis, whereas the synthetic utility of SORI-CAD appears to be largely limited to the cleavage of phenyl-iodine bonds. Hence, laser photolysis greatly expands the variety of substituted phenyl radicals and biradicals that can be synthesized inside a mass spectrometer.     

On the location of conical intersections in CH2BrCl using MS-CASPT2 methods

Multiconfigurational second-order perturbation theory has been employed to calculate two-dimensional potential energy surfaces for the lowest low-lying singlet electronic states of CH2BrCl as a function of the two carbon-halogen bonds. The photochemistry of the system is controlled by a nonadiabatic crossing occurring between the A and B bands, attributed to the b1A' and c1A' states, which are found almost degenerate and forming a near-degeneracy line of almost equidistant C-Br and C-Cl bonds. A crossing point in the near-degeneracy line is identified as a conical intersection in this reduced two-dimensional space. The positions of the conical intersection located at CASSCF, single-state (SS)-CASPT2, and multistate (MS)-CASPT2 levels of theory are compared, also paying attention to the nonorthogonality problem of perturbative approaches. To validate the presence of the conical intersection versus an avoided crossing, the geometrical phase effect has been checked using the multiconfigurational MS-CASPT2 wave function.     

Glassy carbon modified by a silver-palladium alloy: cheap and convenient cathodes for the selective reductive homocoupling of alkyl iodides

Micrometer-thick layers of silver-palladium alloy were elaborated in order to modify the surface of glassy carbon electrodes. Such a surface modification can be readily achieved via a preliminary silver galvanostatic deposit onto carbon followed by a ‘palladization’ step, thanks to a simple immersion in acidic Pd^II-based solutions producing a displacement reaction. The as-prepared metallic interfaces exhibit outstanding catalytic capabilities especially in the cleavage of carbon-halogen bonds while being chemically/electrochemically quite stable and relatively inexpensive. More specifically, the use of such glassy carbon/Ag-Pd electrodes in dimethylformamide (DMF) containing tetraalkylammonium salts (TAA⁺X⁻) makes the one-electron reductions of primary alkyl iodides possible; this reduction leads to the formation of homodimers in high yields. Formation of a free radical as transient resulted from the homocoupling reaction.     

Thermal decomposition of copolymers of styrene and halogenated monomers

Copolymers of 1,2,2,2-tetrachloroethyl esters of unsaturated acids and halogenated N-phenyl maleimides with styrene were pyrolyzed; volatile products were analyzed with a mass spectrometer combined with a gas chromatograph. Hydrogen halide and carbon dioxide in the volatile products were determined during the thermal decomposition of copolymers in glass ampoules; the acyl chloride groups were determined in the residues. The thermal decomposition of copolymers of tetrachloroethyl esters with styrene sets in at ca. 230° by the release of chloral from the copolymer and splitting of some of the CCl bonds in the copolymer. The decomposition of copolymers of styrene with halogenated N-phenyl maleimides starts above 300° by depolymerization of the polystyrene chain sections and by splitting of some of the carbon-halogen bonds. At 310 and 500° for copolymers of tetrachloroethyl esters and at 500° for halogenated N-phenyl maleimides, there is radical dehydrohalogenation of the copolymers, with depolymerization of polystyrene blocks and splitting of carbon-carbon bonds in the main chain.     

Hierarchy in the Halogen Activation During Surface-Promoted Ullmann Coupling

Within the collection of surface-supported reactions currently accessible for the production of extended molecular nanostructures under ultra-high vacuum, Ullmann coupling has been the most successful in the controlled formation of covalent single C−C bonds. Particularly advanced control of this synthetic tool has been obtained by means of hierarchical reactivity, commonly achieved by the use of different halogen atoms that consequently display distinct activation temperatures. Here we report on the site-selective reactivity of certain carbon-halogen bonds. We use precursor molecules halogenated with bromine atoms at two non-equivalent carbon atoms and found that the Ullmann coupling occurs on Au(111) with a remarkable predilection for one of the positions. Experimental evidence is provided by means of scanning tunneling microscopy and core level photoemission spectroscopy, and a rationalized understanding of the observed preference is obtained from density functional theory calculations.     

Polarographisches Verhalten von Pesticiden mit Organohalogenbindungen

Summary The dp-polarographic behaviour of different pesticides with carbon-halogen bonds was investigated in dimethylsulfoxide and methanol/water as solvents; the peak-potentials are demonstrated graphically. From peak-height the pesticides are detectable up to 100 ng · ml^–1. The investigations are of interest for the development of multistage-combined procedures by h.p.l.c. with amperometric detection.

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Herrn Prof. Dr. R. Neeb zum 60. Geburtstag gewidmet     

Oxidative Addition Step in Reactions Involving Palladium Activation of Carbon-Halogen and Carbon-Oxygen Bonds

Different modifications of the Heck reaction involving the activation of carbon-halogen and carbon-oxygen bonds by palladium (styrene phenylation with iodobenzene or benzoic anhydride and iodobenzene carbonylation, reductive coupling, and reduction) are studied by in situ ³¹P NMR spectroscopy. The catalytic cycles of the reactions include oxidative addition to Pd(0) formed in situ. The product composition in this step depends strongly on the composition of the reaction mixture, which is related to PhX conversion in the main catalytic process and with the nature of the catalyst precursor. A new hypothesis as to the mechanism of the catalytic cycle in alkene arylation in the presence of phosphine ligands is suggested. This hypothesis is consistent with NMR monitoring data and with the value of the kinetic isotope effect.__________Translated from Kinetika i Kataliz, Vol. 46, No. 4, 2005, pp. 529–535.Original Russian Text Copyright © 2005 by Shmidt, Smirnov.     

Preparation of lithium stannide mixtures in organic solvents. A alternate source of lithium in organolithium chemistry

Lithium stannides were prepared from lithium naphthalenide and tin (II) chloride or tin (0) powder in THF solvent at room temperature under dry argon atmosphere. They were characterized with elemental analysis, XRD, and solid ^6,7Li NMR. Stabilities and reactivities of lithium stannides prepared from different conditions were tested and showed they were stable for a limited time at low temperatures. Best reactivity was obtained when they were prepared from tin (II) chloride and an excess of lithium naphthalenide. The lithium stannide mixture can reductively cleave carbon-halogen bonds and yield pinacol coupling with aldehydes. Organolithium compounds prepared from lithium stannides and organic halides add to ketones or aldehydes under Barbier conditions.     

Hydrogen atom abstraction and solvent involvement in the electrochemistry of haloaromatics: Reduction of 4-bromobenzophenone in dimethylsulfoxide

Haloaromatics, ArX, can be divided into two main classes according to their electrochemical behavior. In the first one, the apparent number of electrons is two and the reduction consists in an hydrogenolysis of the carbon-halogen bond leading quantitatively to ArH. In the second group the number of electrons per molecule is less than two and the yield in ArH is significantly less than 100%. 4-Bromobenzophenone was selected as a model compound for a detailed study of this latter behavior. Besides ArH five other reaction products were identified and titrated in the electrolyzed solution. A reduction mechanism accounting for the nature and yields of the reaction products is proposed on the basis of polarographic, voltammetric and coulometric data, on deuteration experiments and on a careful analysis of product distribution. It involves, after dehalogenation of the initial anion radical, Ar^. hydrogen atom abstraction from the solvent. The solvent radical thus formed is reduced into the corresponding anion which adds to Ar^. leading to a solvent substituted benzophenone anion radical which then evolves to various secondary products. Competition between H-atom transfer, electrode and solution electron transfer and addition of a solvent molecule is discussed as a function of the structure of the substrate.     

Addition of electrophilic and heterocyclic carbon-centered radicals to glyoxylic oxime ethers

[reaction: see text] Stabilized primary radicals can be formed from alkyl halides in an atom transfer process with Et(3)B. This process depends on the strength of the carbon-halogen bond and the stability of the resulting primary radical. Radicals formed from benzyl iodide and ethyl iodoacetate add to glyoxylic oxime ethers; however, more electrophilic radicals do not. Glyoxylic oxime ethers are also good radical acceptors for heterocyclic carbon-centered secondary radicals, giving novel alpha-amino acid derivatives.     

Electrochemical reduction of 5,5′-dichlorohydurilic acid. mechanism and analytical applications

The electrochemical reduction of 5,5′-dichlorohydurilic acid has been studied at the dropping mercury electrode (DME) and the pyrolytic graphite electrode (PGE). At the DME the single polarographic reduction wave observed at pH 6–11 involves a direct 4e—2H⁺ reduction of the carbon-halogen bond to give hydurilic acid and chloride. The state of hydration or ionization of the 5,5′-dichlorohydurilic acid has no effect on the electrochemical reaction. At the PGE, 5,5′-dichlorohydurilic acid shows two voltammetric peaks. Peak I_c, observed between pH 5 and 7, arises from an overall 4e—2H⁺ reduction of 5,5′-dichlorohydurilic acid via a mechanism that involves initial electron attack at a carbonyl group alpha to a carbon-halogen bond with simultaneous elimination of chloride ion. The peak II_c process involves an initial 2e—1H⁺ reduction of a partially hydrated form of 5,5′-dichlorohydurilic acid with only one unhydrated halocarbonyl moiety available for reaction. Attack is again via the carbonyl group with simultaneous elimination of chloride and formation of 5-chlorohydurilic acid. A chemical dehydration step then occurs with a rate constant of ca. 0.24 s^?1 at pH 8.2, with formation of a further reducible halocarbonyl group. This is again reduced in an overall 2e—2H⁺ reaction to give hydurilic acid and chloride ion. The peak II_c process hence proceeds via an ECE mechanism. The different mechanisms observed for reduction of 5,5′-dichlorohydurilic acid at mercury and pyrolytic graphite electrodes are unusual. Analytical methods have been developed for the polarographic determination of 5,5′-dichlorohydurilic acid via its reduction wave at the DME, and for the voltammetric determination of hydurilic acid via its first oxidation peak at the PGE.     

Facile identification of photocleavable reactive metabolites and oxidative stress biomarkers in proteins via mass spectrometry

Described herein is a method which combines bond selective fragmentation by photodissociation with online liquid chromatographic separation and mass spectrometric analysis. Photoexcitation of proteins or peptides with 266-nm light does not normally yield abundant fragmentation; however, incorporation of a suitable carbon-sulfur or carbon-halogen bond that is proximal to a chromophore allows access to direct dissociation pathways, resulting in homolytic cleavage of these bonds. Radicals generated through this process can cause further dissociation of the peptide backbone, which is useful for site specifically identifying the point of modification. Two specific applications of this technique for peptide analysis in model systems are presented: (1) identification of reactive metabolites which covalently modify cysteine residues, and (2) characterization of halogenated tyrosine residues which are biomarkers related to oxidative stress. In both cases, these naturally occurring post translational modifications create photocleavable bonds which can be fragmented by 266-nm light. The selectivity offered by photodissociation allows facile identification of the peptides of interest even in complex mixtures, and subsequent selective radical directed backbone fragmentation pinpoints the site of modification. This combination greatly simplifies data analysis and provides more confident assignments.     

Intrinsic acidity of dimethylhalonium ions: evidence for hyperconjugation in dimethylhalonium ylides in the gas phase

The intrinsic acidity of dimethylhalonium ions has been determined, both by theoretical methods and by gas-phase reactions of the isolated ions with pyridine bases. The calculated geometry of the dimethylhalonium ions shows a bent structure with the C-X-C angle decreasing in the order Cl > Br > I. Thermochemical calculations for the reaction of the dimethylhalonium ions with pyridine, 2,6-dimethylpyridine, and 2,6-di-tert-butylpyridine indicate that proton transfer, with the formation of the dimethylhalonium ylide is endothermic, whereas methyl transfer, with formation of methylhalide, is exothermic. The endothermicities for proton transfer are, nevertheless, dependent on the steric hindrance of the base. The bulkier the bases, the less endothermic the proton-transfer reaction is. Experimental gas-phase reactions support the calculations, showing that methyl transfer is the major reaction of dimethylchloronium and dimethyliodonium with pyridine, whereas proton transfer, as well as single electron transfer, is observed for the bulkier bases. The calculations also indicate that acidity increases in the order chloronium > bromonium > iodonium. NBO calculations predict that hyperconjugation with the sigma carbon-halogen orbital plays a role in stabilizing the halonium ylide species in the gas phase.     

Metal-metal and carbon-carbon bonds as potential components of molecular batteries

The reductive coupling of [M(salophen)] derivatives, where M is an early transition metal and salophen is N,N'-o-phenylenebis(salicylideneaminato) dianion, led to the formation of dimers linked through C-C and M-M bonds. Both of these bonds can potentially function as electron reservoirs: each bond can be used as a reversible source of a pair of electrons under the condition that it is not chemically transformed by the incoming substrate which functions as an electron acceptor. To explore this potential function as well as the competition in the redox processes between C-C and M-M bonds within the same molecular framework, we investigated the reduction of [(tBu4-salophen)NbCl3] (1) and [(tBu4-salophen)MoCl2] (7) as model compounds. In the former case, the reduction led to [(Nb-Nb)(tBu4-*salophen2*)] (2) which contains both a Nb-Nb bond (2.6528(7) A) and two C-C bonds across two imino groups of the ligand. Complex 2 can be reduced further to a transient compound 5 that contains an Nb=Nb bond. In the second case, the reduction of 7 by two electrons led to [(Mo[triplebond]Mo)(tBu4-salophen)2] (8), which does not contain any C-C linkages between the two salophen units. Complexes 2 and 5 are able to transfer one pair and two pairs of electrons, respectively, to give compounds 3, 4, and 6, with the consequent cleavage of the Nb-Nb and Nb=Nb bonds. In the present case, it is surprising that the C-C bonds do not participate in the reduction of the substrates. A careful theoretical treatment anticipates, both in the case of 1 and 7, the preferential formation of metal-metal bonds upon reduction. This is indeed the case for 7, but not for 1, where the formation of C-C bonds competes with that of M-M bonds, the latter being the first ones, however, to be involved in electron-transfer reactions. The theoretical approach allowed us to investigate the possibility of intramolecular electron transfer from C-C bonds to M-M bonds and vice versa.