Cuprous Oxide Catalyzed Oxidative CC Bond Cleavage for CN Bond Formation: Synthesis of Cyclic Imides from Ketones and Amines

Selective oxidative cleavage of a C? C bond offers a straightforward method to functionalize organic skeletons. Reported herein is the oxidative C? C bond cleavage of ketone for C? N bond formation over a cuprous oxide catalyst with molecular oxygen as the oxidant. A wide range of ketones and amines are converted into cyclic imides with moderate to excellent yields. In‐depth studies show that both α‐C? H and β‐C? H bonds adjacent to the carbonyl groups are indispensable for the C? C bond cleavage. DFT calculations indicate the reaction is initiated with the oxidation of the α‐C? H bond. Amines lower the activation energy of the C? C bond cleavage, and thus promote the reaction. New insight into the C? C bond cleavage mechanism is presented.     

Cuprous Oxide Catalyzed Oxidative C?C Bond Cleavage for C?N Bond Formation: Synthesis of Cyclic Imides from Ketones and Amines

Selective oxidative cleavage of a C C bond offers a straightforward method to functionalize organic skeletons. Reported herein is the oxidative C C bond cleavage of ketone for C N bond formation over a cuprous oxide catalyst with molecular oxygen as the oxidant. A wide range of ketones and amines are converted into cyclic imides with moderate to excellent yields. In‐depth studies show that both α‐C H and β‐C H bonds adjacent to the carbonyl groups are indispensable for the C C bond cleavage. DFT calculations indicate the reaction is initiated with the oxidation of the α‐C H bond. Amines lower the activation energy of the C C bond cleavage, and thus promote the reaction. New insight into the C C bond cleavage mechanism is presented.     

一种切断酰胺C—N键的简便方法

研究了一种质子酸和Lewis酸共同催化酰胺C—N键断键的新方法,讨论了温度,CuCl2量以及Lewis酸种类对C—N键断键率的影响,并提出了在此条件下酰胺C—N键断裂的可能机理.新方法反应温度低、耗酸量小、条件温和.     

Photochemistry of 2-(1-naphthyl)-2H-azirines in matrixes and in solutions: wavelength-dependent C-C and C-N bond cleavage of the azirine ring

The photochemistry of 3-methyl-2-(1-naphthyl)-2H-azirine (1a) was investigated by the direct observation of reactive intermediates in matrixes at 10 K and by the characterization of reaction products in solutions. As already reported, the photolysis of the azirine 1a with the short-wavelength light (>300 nm) caused the C-C bond cleavage of the 2H-azirine ring to produce the nitrile ylide 2. However, the products derived from the C-N bond cleavage were exclusively obtained in the irradiation of 1a with the long-wavelength light (366 nm) both in matrixes and in solutions. When 1a was irradiated in the presence of O(2) with the long-wavelength light, acetonitrile oxide (6) was produced through the capture of the biradical 4 generated by the C-N bond cleavage of 1a with O(2). An introduction of a nitro group into the naphthyl ring of 1a resulted in an acceleration of the decomposition in the long-wavelength irradiation and an extension of the wavelength region where the products derived from the C-N bond cleavage were selectively obtained. On the basis of molecular orbital calculations with the INDO/S method, the reason for the wavelength-dependent selective C-C and C-N bond cleavage of the azirine ring of 1a is discussed.     

Potential energy surface discontinuities in local correlation methods

We have examined the occurrence of discontinuities in bond-breaking potential energy surfaces given by local correlation methods based on the Pulay-Saeb? orbital domain approach. Our analysis focuses on three prototypical dissociating systems: the C-F bond in fluoromethane, the C-C bond in singlet, ketene, and the central C-C bond in propadienone. We find that such discontinuities do not occur in cases of homolytic bond cleavage due to the inability of the Pipek-Mezey orbital localization method to separate singlet-coupled charges on distant fragments. However, for heterolytic bond cleavage, such as that observed in singlet ketene and propadienone, discontinuities occur both at stretched geometries and near equilibrium. These discontinuities are usually small, but may be of the same order of magnitude as the localization error in some cases.     

Palladium-catalyzed conjugate addition to electron-deficient alkynes with benzenesulfinic acid derived from 1,2-bis(phenylsulfonyl)ethane: selective synthesis of (E)-vinyl sulfones

A new, selective method for the synthesis of (E)-vinyl sulfones is presence by palladium-catalyzed C-S bond cleavage/conjugate addition. In the presence of Pd(OAc)(2) and DMEDA (N(1),N(2)-dimethylethane-1,2-diamine), 1,2-bis(phenylsulfonyl)ethane underwent the C-S bond cleavage, followed by conjugate addition to numerous electron-deficient alkynes afforded the corresponding (E)-vinyl sulfones in moderate to good yields.     

Trapping-mediated dissociative chemisorption of cycloalkanes on Ru(001) and Ir(111): influence of ring strain and molecular geometry on the activation of C-C and C-H bonds.

We have measured the initial probabilities of dissociative chemisorption of perhydrido and perdeutero cycloalkane isotopomers on the hexagonally close-packed Ru(001) and Ir(111) single-crystalline surfaces for surface temperatures between 250 and 1100 K. Kinetic parameters (activation barrier and preexponential factor) describing the initial, rate-limiting C-H or C-C bond cleavage reactions were quantified for each cycloalkane isotopomer on each surface. Determination of the dominant initial reaction mechanism as either initial C-C or C-H bond cleavage was judged by the presence or absence of a kinetic isotope effect between the activation barriers for each cycloalkane isotopomer pair, and also by comparison with other relevant alkane activation barriers. On the Ir(111) surface, the dissociative chemisorption of cyclobutane, cyclopentane, and cyclohexane occurs via two different reaction pathways: initial C-C bond cleavage dominates on Ir(111) at high temperature (T > approximately 600 K), while at low temperature (T < approximately 400 K), initial C-H bond cleavage dominates. On the Ru(001) surface, dissociative chemisorption of cyclopentane occurs via initial C-C bond cleavage over the entire temperature range studied, whereas dissociative chemisorption of both cyclohexane and cyclooctane occurs via initial C-H bond cleavage. Comparison of the cycloalkane C-C bond activation barriers measured here with those reported previously in the literature qualitatively suggests that the difference in ring-strain energies between the initial state and the transition state for ring-opening C-C bond cleavage effectively lowers or raises the activation barrier for dissociative chemisorption via C-C bond cleavage, depending on whether the transition state is less or more strained than the initial state. Moreover, steric arguments and metal-carbon bond strength arguments have been evoked to explain the observed trend of decreasing C-H bond activation barrier with decreasing cycloalkane ring size.     

A novel salt bridge mechanism highlights the need for nonmobile proton conditions to promote disulfide bond cleavage in protonated peptides under low-energy collisional activation

The gas-phase fragmentation mechanisms of small models for peptides containing intermolecular disulfide links have been studied using a combination of tandem mass spectrometry experiments, isotopic labeling, structural labeling, accurate mass measurements of product ions, and theoretical calculations (at the MP2/6-311 + G(2d,p)//B3LYP/3-21G(d) level of theory). Cystine and its C-terminal derivatives were observed to fragment via a range of pathways, including loss of neutral molecules, amide bond cleavage, and S-S and C-S bond cleavages. Various mechanisms were considered to rationalize S-S and C-S bond cleavage processes, including charge directed neighboring group processes and nonmobile proton salt bridge mechanism. Three low-energy fragmentation pathways were identified from theoretical calculations on cystine N-methyl amide: (1) S-S bond cleavage dominated by a neighboring group process involving the C-terminal amide N to form either a protonated cysteine derivative or protonated sulfenyl amide product ion (44.3 kcal mol(-1)); (2) C-S bond cleavage via a salt bridge mechanism, involving abstraction of the alpha-hydrogen by the N-terminal amino group to form a protonated thiocysteine derivative (35.0 kcal mol(-1)); and (3) C-S bond cleavage via a Grob-like fragmentation process in which the nucleophilic N-terminal amino group forms a protonated dithiazolidine (57.9 kcal mol(-1)). Interestingly, C-S bond cleavage by neighboring group processes have high activation barriers (63.1 kcal mol(-1)) and are thus not expected to be accessible during low-energy CID experiments. In comparison to the energetics of simple amide bond cleavage, these S-S and C-S bond cleavage reactions are higher in energy, which helps rationalize why bond cleavage processes involving the disulfide bond are rarely observed for low-energy CID of peptides with mobile proton(s) containing intermolecular disulfide bonds. On the other hand, the absence of a mobile proton appears to "switch on" disulfide bond cleavage reactions, which can be rationalized by the salt bridge mechanism. This potentially has important ramifications in explaining the prevalence of disulfide bond cleavage in singly protonated peptides under MALDI conditions.     

C−C Bond‐Forming Strategy by Manganese‐Catalyzed Oxidative Ring‐Opening Cyanation and Ethynylation of Cyclobutanol Derivatives

A novel C?C bond‐forming strategy employing manganese‐catalyzed ring‐opening of cyclobutanol substrates, followed by cyanation or ethynylation, is described. A cyano C1 unit and ethynyl C2 unit are regiospecifically introduced to the γ‐position of ketones at room temperature, providing a mild yet powerful method for production of elusive aliphatic nitriles and alkynes. All transformations described are based on a common sequence: 1) oxidative ring‐opening of cyclobutanol substrates by C?C bond cleavage; 2) radical addition to triple bonds bearing an arylsulfonyl group; and 3) radical‐mediated C?S bond cleavage.     

A combined nuclear magnetic resonance and computational study of monohydroxyflavones applied to product ion mass spectra

A method is presented for the estimation of 13C-chemical shifts for carbon atoms in protonated and deprotonated molecules; in principle, this method can be applied to ions in general. Experimental 13C-chemical shifts were found to vary linearly with computed atomic charges using the PM3 method. Pseudo-13C-chemical shifts for atoms in protonated and deprotonated molecules can be estimated from computed atomic charges for such atoms using the above linear relationship. The pseudo-13C-chemical shifts obtained were applied to the rationalization of product ion mass spectra of protonated and deprotonated molecules of flavone and 3-, 5-, 6-, 7-, 2'-, 3'-, and 4'-hydroxyflavones, where product ion formation is due to either cross-ring cleavage of the C-ring (retro-Diels-Alder reaction) or to cleavage of a C-ring bond followed by loss of either a small neutral molecule or a radical. The total product ion abundance ratio of C-ring cross cleavage to C-ring bond cleavage, gamma, varied by a factor of 660 for deprotonated monohydroxyflavones, i.e., from 0.014:1 to 9.27:1. The magnitude of gamma, which is dependent on the relative bond orders within the C-ring of the protonated and deprotonated molecules of monohydroxyflavones, can be rationalized on the basis of the magnitudes of the 13C- and 1H-chemical shifts as determined by nuclear magnetic resonance spectroscopy.     

Application of MALDI TOF/TOF mass spectrometry and collision-induced dissociation for the identification of disulfide-bonded peptides

This paper describes a method for the fast identification and composition of disulfide-bonded peptides. A unique fragmentation signature of inter-disulfide-bonded peptides is detected using matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF)/TOF mass spectrometry and high-energy collision-induced dissociation (CID). This fragmentation pattern identifies peptides with an interconnected disulfide bond and provides information regarding the composition of the peptides involved in the pairing. The distinctive signature produced using CID is a triplet of ions resulting from the cleavage of the disulfide bond to produce dehydroalanine, cysteine or thiocysteine product ions. This method is not applicable to intra-peptide disulfide bonds, as the cleavage mechanism is not the same and a triplet pattern is not observed. This method has been successfully applied to identifying disulfide-bonded peptides in a number of control digestions, as well as study samples where disulfide bond networks were postulated and/or unknown.     

Mechanism of bleomycin suicide: a Car-Parrinello molecular dynamics investigation

Using first-principles molecular dynamics simulations (Car-Parrinello method) we investigated the possible reaction pathways for decay of the active bleomycin-Fe(III)-OOH complex, so-called bleomycin suicide. The theoretical model of activated bleomycin contains the whole metal bonding domain of the bleomycin ligand. Simulations performed both in a vacuum and in water show that a facile decaying process involves a homolytic O-O bond cleavage with an almost simultaneous hydrogen atom abstraction. The formation of an intra- or intermolecular hydrogen bond appears to be crucial for the decay of the activated bleomycin. We did not observe any evidence of heterolytic cleavage of the O-O bond of the Fe(III)-OOH species.     

硅胶担载的高锰酸钾对烯烃碳碳双键的氧化

在无有机溶剂做介质的条件下，用硅胶吸附的高锰酸钾氧化6种难溶于水的液态烯烃，得到了双键发生断裂的氧化产物。该反应操作简便，反应快，收率好。此外，对硅胶的活化作用机制进行了浅要。     

铑催化合成气制乙醇反应中CO断键途径的研究

利用程序升温表面反应─红外（ＴＰＳＲ－ＩＲ）动态技术考察ＣＯ吸附物种对氢的反应性能并检验表面反应生成的中间物，结果表明线式ＣＯ对氢的反应性能高于桥式ＣＯ，即线式ＣＯ更可能是活性吸附态；表面反应生成了ＨＣＯ、ＣＨ２等中间物．用键级守恒（ＢＯＣ）－Ｍｏｒｓｅ势方法计算比较了ＣＯ→ＣＨ２过程中各可能基元步骤在Ｒｈ（１１１）面上的反应活化能和反应热，结果表明ＣＯ经其部分氢化物种（如Ｈ２ＣＯ、ＨＣＯＨ）的氢解反应断裂Ｃ─Ｏ键在能量上最有利．根据这些实验结果，提出铑基催化剂上合成气转化反应主要按缔合式机理进行；ＣＯ的优势断键途径为先部分氢化，而后氢助断键．     

Iridium‐Catalyzed Reductive Carbon–Carbon Bond Cleavage Reaction on a Curved Pyridylcorannulene Skeleton

The cleavage of C? C bonds in π‐conjugated systems is an important method for controlling their shape and coplanarity. An efficient way for the cleavage of an aromatic C? C bond in a typical buckybowl corannulene skeleton is reported. The reaction of 2‐pyridylcorannulene with a catalytic amount of IrCl₃?n H₂O in ethylene glycol at 250 °C resulted in a structural transformation from the curved corannulene skeleton to a strain‐free flat benzo[ghi]fluoranthene skeleton through a site‐selective C? C cleavage reaction. This cleavage reaction was found to be driven by both the coordination of the 2‐pyridyl substituent to iridium and the relief of strain in the curved corannulene skeleton. This finding should facilitate the design of carbon nanomaterials based on C? C bond cleavage reactions.     

Combined use of platinum(II) complexes and palladium(II) complexes for selective cleavage of peptides and proteins

This study shows, for the first time, the advantages of combining two transition-metal complexes as selective proteolytic reagents. In this procedure, cis-[Pt(en)(H(2)O)(2)](2+) is followed by [Pd(H(2)O)(4)](2+). In the peptide AcAla-Lys-Tyr-Gly-Gly-Met-Ala-Ala-Arg-Ala, the Pt(II) reagent cleaves the Met6-Ala7 peptide bond, whereas the Pd(II) reagent cleaves the Gly4-Gly5 bond. In the peptide AcVal-Lys-Gly-Gly-His-Ala-Lys-Tyr-Gly-Gly-Met-Ala-Ala-Arg-Ala, the Pt(II) reagent cleaves the Met11-Ala12 peptide bond, whereas the Pd(II) reagent cleaves the Gly3-Gly4 bond. All cleavage reactions are regioselective and complete at pH 2.0 and 60 degrees C. Each metal ion binds to an anchoring side chain and then, as a Lewis acid, activates a proximal peptide bond toward hydrolysis by the solvent water. The selectivity in cleavage is a consequence of the selectivity in this initial anchoring. Both Pt(II) and Pd(II) reagents bind to the methionine side chain, whereas only the Pd(II) reagent binds to the histidine side chain under the reaction conditions. Consequently, only methionine residues direct the cleavage by the Pt(II) reagent, whereas both methionine and histidine residues direct the cleavage by the Pd(II) reagent. The Pt(II) reagent cleaves the first bond downstream from the anchor, i.e., the Met-Z bond. The Pd(II) reagent cleaves the second bond upstream from the anchor, i.e., the X-Y bond in the X-Y-Met-Z and in the X-Y-His-Z segments. The diethylenetriamine complex [Pt(dien)(H(2)O)](2+) cannot promote cleavage. Its prior binding to the Met11 residue in the second peptide prevents the Pd(II) reagents from binding to Met11 and cleaving the Gly9-Gly10 bond and directs the cleavage by the Pd(II) reagent exclusively at the Gly3-Gly4 bond. Our new method was tested on equine myoglobin, which contains 2 methionine residues and 11 histidine residues. The complete methionine-directed cleavage of the Met55-Lys56 and Met131-Thr132 bonds by the Pt(II) reagent produced three fragments, suitable for various biochemical applications because they are relatively long and contain amino and carboxylic terminal groups. The deliberately incomplete histidine-directed cleavage of the long fragments 1.55 and 56.131 at many sites by the Pd(II) reagent produced numerous short fragments, suitable for protein identification by mass spectrometry. The ability of combined Pt(II) and Pd(II) complexes to cleave proteins with explicable and adjustable selectivity and with good yields bodes well for their greater use in biochemical and bioanalytical practice.     

A new approach to the synthesis of aliphatic triamines and diamino alcohols that are analogs of the anti-TB drug ethambutol

A method for the synthesis of diastereomerically pure diamino alcohols and triamines was developed. The products obtained are new asymmetric structural analogs of the anti-TB drug ethambutol. The method involves reductive cleavage of the N-N bond in appropriate functionalized pyrazolidines and 2-pyrazolines under the action of a diborane complex with THF. The cleavage occurs with retention of the configurations of the asymmetric centers of the starting compounds.     

Unexpected copper-catalyzed aerobic oxidative cleavage of C(sp3)-C(sp3) bond of glycol ethers

An unexpected Cu-catalyzed oxidative cleavage of the C(sp(3))-C(sp(3)) bond in glycol ethers by using air or molecular oxygen as the terminal stoichiometric oxidant is demonstrated. As a result, the corresponding α-acyloxy ethers and formates of 1,2-ethanediol are formed by direct coupling of carboxylic acids and aldehydes with glycol ethers under the reaction conditions. This method represents the first example of Cu-catalyzed aerobic cleavage of saturated C-C bond in ethers.     

A new synthetic route for 1,2-diketo compounds using unexpected C-C bond cleavage by PCC

An efficient method has been established for the preparation of 1,2-diketones by unexpected C-C bond cleavage in 4-keto-2-hydroxy esters using pyridiniumchlorochromate (PCC).     

Iron‐Catalyzed Radical Cleavage/C−C Bond Formation of Acetal‐Derived Alkylsilyl Peroxides

A novel radical‐based approach for the iron‐catalyzed selective cleavage of acetal‐derived alkylsilyl peroxides, followed by the formation of a carbon–carbon bond is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the acetal moiety and the carbon electrophile. Mechanistic studies suggest that the present reaction proceeds through a free‐radical process involving carbon radicals generated by the homolytic cleavage of a carbon–carbon bond within the acetal moiety. A synthetic application of this method to sugar‐derived alkylsilyl peroxides is also described.