Carbon Bond Formation Research Articles

Carbon–Carbon Bond Formation at the Reducing End of Unprotected Oligosaccharides

Carbon–Carbon Bond Formation at the Reducing End of Unprotected Oligosaccharides

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis.

Thiamin diphosphate (ThDP)-dependent enzymes constitute a large class of enzymes that catalyze a diverse range of reactions. Many are involved in stereospecific carbon–carbon bond formation and, consequently, have found increasing interest and utility as chiral catalysts in various biocatalytic applications. All ThDP-catalyzed reactions require the reaction of the ThDP ylide (the activated state of the cofactor) with the substrate. Given that the cofactor can adopt up to seven states on an enzyme, identifying the factors affecting the stability of the pre-reactant states is important for the overall understanding of the kinetics and mechanism of the individual reactions.In this paper we use density functional theory calculations to systematically study the different cofactor states in terms of energies and geometries. Benzoylformate decarboxylase (BFDC), which is a well characterized chiral catalyst, serves as the prototypical ThDP-dependent enzyme. A model of the active site was constructed on the basis of available crystal structures, and the cofactor states were characterized in the presence of three different ligands (crystallographic water, benzoylformate as substrate, and (R)-mandelate as inhibitor). Overall, the calculations reveal that the relative stabilities of the cofactor states are greatly affected by the presence and identity of the bound ligands. A surprising finding is that benzoylformate binding, while favoring ylide formation, provided even greater stabilization to a catalytically inactive tricyclic state. Conversely, the inhibitor binding greatly destabilized the ylide formation. Together, these observations have significant implications for the reaction kinetics of the ThDP-dependent enzymes, and, potentially, for the use of unnatural substrates in such reactions.

Relationship between ferromagnetism and formation of complex carbon bonds in carbon doped ZnO powders.

We have investigated the possible relationship between defects, carbon bonds and the associated magnetic properties of carbon doped ZnO powders with intentional nominal carbon concentrations of 0, 1, 3, 5, 8 and 10 mol%. The samples were prepared by mechanical milling assisted by solid state reaction and carefully characterized using different techniques. X-ray diffraction and micro-Raman analysis revealed structural changes below and above the nominal carbon doping concentration of 3 mol% along with formation of intrinsic defect complexes. It was found that the oxygen and zinc content and the band gap of ZnO gradually decrease with increasing carbon content. XPS studies revealed the formation of Zn-O-C and O-C-O bonds and partial substitution of oxygen by carbon, in the form of Zn-C in all samples. When the nominal doping concentration increased above 3 mol%, formation of C-Zn-C bonds was drastically increased. The undoped ZnO sample was diamagnetic and free pure graphitic carbon was paramagnetic, while the 3 mol% carbon doped ZnO sample displayed the maximum saturation magnetization. The room temperature ferromagnetism (RTFM) has been ascribed to the presence of Zn-O-C, O-C-O and O-Zn-C bonds, where oxygen atoms may play a crucial role for mediating the long range magnetic interaction. C-Zn-C bonds decrease the saturation magnetization by encouraging antiferromagnetic behavior and the formation of intrinsic defects related with the carbon doping seem to have no influence on the RTFM observed.

Metal-free visible light photoredox enables generation of carbyne equivalents via phosphonium ylide C-H activation.

Carbyne, an interesting synthetic intermediate, has recently been generated from hypervalent iodine precursors via photoredox catalysis. Given the underexplored chemistry of carbyne, due to the paucity of carbyne sources, we are intrigued to discover a new source for this reactive species from classical reagents - phosphonium ylides. Our novel strategy employing phosphonium ylides in an olefin hydrocarbonation reaction features a facile approach for constructing carbon-carbon bonds through metal-free and benign reaction conditions. Moreover, the hydrocarbonation products were delivered in a highly regioselective manner.

Hypervalent iodine reactions utilized in carbon-carbon bond formations.

Advances in hypervalent iodine chemistry have put the field on the precipice of a second golden age; the first being pioneered in the 1990s. During that period, C-C bond forming reactions would be published but rarely with the intended goal of developing a C-C bond forming methodology. More recently, the development of hypervalent iodine-guided electrophilic substitution, arylations using hypervalent iodine, and photoredox reactions with hypervalent iodine have shown great progress in the area of C-C bond formation.

Visible-light induced enhancement in the multi-catalytic activity of sulfated carbon dots for aerobic carbon–carbon bond formation

The development of carbonaceous materials as metal-free catalysts integrating different types of catalysis in a single system represents a significant advance in cascade/tandem organic synthesis.

Mild polyaddition and polyalkylation based on the carbon-carbon bond formation reaction of active methylene.

The Michael addition and alkylation reaction of active methylene compounds (AMCs) with two active hydrogens had been investigated extensively in organic chemistry, while the polymerization of AMCs had few studies. Herein, we reported active methylene-based polyaddition and polyalkylation catalyzed via an organic superbase under ambient conditions. A model polymerization was first conducted between ethylene glycol diacrylate (EGDA) and methyl cyanoacetate (MCA). The molecular weight (Mw) of the model polymer was up to 50 500 g mol−1 with a high yield (99%). Eight AMCs were selected and a high-throughput parallel synthesizing instrument (HTPSI) was used to synthesize semi-library polymers of AMCs and EGDA via a Michael type polyaddition. The obtained AMC-based polymers had low cell cytotoxicity. Elastomers with cyanogen groups could be prepared using trimethylolpropane triacrylate (TMPTA) as a crosslinker. Furthermore, three dihalogen compounds were explored to polymerize with MCA and malononitrile via alkylation reactions. The pendent cyanogen or ester groups of the polymers could be reduced by lithium aluminum hydride. Novel polymer families were constructed based on the polyaddition and polyalkylation of AMCs.

Photocatalytic Cycloadditions Enabled by a Lithium Perchlorate/Nitromethane Electrolyte Solution

Photocatalytic cycloadditions involving carbon–carbon bond formation in the absence of an external sensitizer are described. The use of a lithium perchlorate/nitromethane electrolyte solution exhibiting remarkable Lewis acidity is the key for the successful transformations. According to the UV/Vis measurements, an electron donor–acceptor complex did not form and nitromethane was expected to function as the initial sensitizer for the reactions. Although the mechanisms are still under debate, both electron‐ and energy‐transfer processes could be involved, both of which are triggered by excited nitromethane in combination with molecular oxygen.

Spectroscopic Characterization and Mechanistic Studies on Visible Light Photoredox Carbon–Carbon Bond Formation by Bis(arylimino)acenaphthene Copper Photosensitizers

Currently, the most popular molecular photosensitizers used for synthetic organic chemistry and energy applications are still the noble-metal-based ruthenium and iridium complexes that usually require expensive metal and ligand precursors. In contrast, bis(arylimino)acenaphthene (Ar-BIAN) is an established redox noninnocent π-accepting ligand that is easily assembled in one condensation step from affordable and commercially available precursors. Herein, we have developed a series of Ar-BIAN CuI complexes as visible-light-harvesting photosensitizers. Notably, one of these panchromatic, homoleptic Ar-BIAN CuI complexes exhibits a radiative recombination lifetime that is longer than diffusion-controlled reactions, as observed by time-correlated single-photon counting spectroscopy. Ar-BIAN CuI facilitates visible-light-promoted atom-transfer radical addition reactions via carbon–carbon bond formation with CBr3 radicals in good yields of up to 75%. Steady-state and transient absorption spectroscopic measuremen...

Photomediated atom transfer radical polymerization of MMA under long-wavelength light irradiation

In this study, a novel photocatalyst, pentarylenebis(dicarboximide) dye: (1,6,13,18-tetra(4-(2,3,3-trimethylbut-2-yl)phenoxy)-N,N’-(2,6-diisopropylphenyl)-pentarylene-3,4,15,16-tetracarboxidiimide) (TTPDPT), was first used in metal-free photoinduced atom transfer radical polymerization (ATRP) of methyl methacrylates (MMA). The initiator was methyl α-bromoisobutyrate (MBI) and the light source was mild near-infrared (NIR) light irradiation (λmax ≈ 870 nm). The TTPDPT-mediated ATRP relies on in situ photoreduction of a MBI through an electron transfer process to generate the desired alkyl radical, which could induce polymerization of the monomer. The photoinduced metal-free ATRP of MMA shows typical characteristics of controlled free radical polymerization, showing the linear evolution of number-average molecular weight (Mn,GPC) with monomer conversion, where polymers with predetermined degree of polymerization have well-controlled molecular weights and narrow molecular weight distribution (Mw/Mn). The photoinduced metal-free ATRP of MMA can be carried out with just ppm level of TTPDPT. The polymerization initiation and propagation can be operated by the aid of pulsed light sequences while NIR light source was used to promote carbon–carbon bond formation and to produce poly(methyl methacrylate) (PMMA) with Mw/Mn as low as 1.5. The synthesized PMMA was characterized by 1H nuclear magnetic resonance (1H NMR). The resultant PMMA contained a bromide end group that can be employed to reinitiate styrene polymerization to produce block copolymers through chain extension experiments.

Visible light-induced reduction system of diphenylviologen derivative with water-soluble porphyrin for biocatalytic carbon–carbon bond formation from CO2

Abstract From the view point of green chemistry, CO2 utilization technologies with solar energy including the photoredox system have been received a lot of attention. As one of them, photoredox system containing a photosensitizer and a catalyst catalyzing a reaction of a carbon–carbon bond formation from CO2 as a feed stock were constructed. In a recent study, we reported the visible light-induced malate (C4 compound) production from pyruvate (C3 compound) and CO2 due to carbon–carbon bond formation with the system consisting an electron donor, a photosensitizer, diphenylviologen (PV2+) derivative as an electron mediator in the presence of malic enzyme (ME). However, the interaction between a photosensitizer and PV2+ derivative has not been clarified yet. In this study, water-soluble PV2+ derivative, 1,1′-bis(p-sulfonatophenyl)-4,4′-bipyridinium salt (PSV2+) was synthesized, and its electro-, photochemical properties were evaluated. Moreover, the photoredox properties of PSV2+ with water-soluble Zn porphyrin were studied using fluorescence spectroscopy and steady state irradiation. The fluorescence of Zn porphyrin was quenched by PSV2+ and the two-electron reduced form of PSV2+ were produced with Zn porphyrin with steady state irradiation. In addition, reaction solution containing triethanolamine, tetraphenylporphyrin tetrasulfonate, pyruvate, ME, Mg2+ and PSV2+ in CO2 saturated bis-tris buffer (pH 7.4) was irradiated with visible light, the oxaloacetate and malate were produced. This result indicates that PSV2+ is an efficient electron mediator in the visible light-induced redox system for carbon–carbon bond formation with ME from CO2 as a feedstock.

Pathways to New Applications for Quantum Control

In 1998, the first successful quantum control experiment with application to a molecular framework was conducted with a shaped laser pulse, optimizing the branching ratio between different organometallic reaction channels. This work induced a vast activity in quantum control during the next 10 years, and different optimization aims were achieved in the gas phase, liquid phase, and even in biologically relevant molecules like light-harvesting complexes. Accompanying and preceding this development were important advances in theoretical quantum control simulations. They predicted several control scenarios and explained how and why quantum control experiments work. After many successful proofs of concept in molecular science, the big challenge is to expand its huge conceptual potential of directly being able to steer nuclear and/or electronic motion to more applied implementations. In this Account, based on several recent advances, we give a personal evaluation of where the field of molecular quantum control is at the moment and especially where we think promising applications can be in the near future. One of these paths leads to synthetic chemistry. The synthesis of novel pharmaceutical compounds or natural products often involves many synthetic steps, each one devouring resources and lowering the product yield. Shaped laser pulses can possibly act as photonic reagents and shorten the synthetic route toward the desired product. Chemical synthesis usually takes place in solution, and by including explicit solvent molecules in our quantum control simulations, we were able to identify their highly inhomogeneous influence on chemical reactions and how this affects potential quantum control. More important, we demonstrated for a synthetically relevant example that these complications can be overcome in theory, and laser pulses can be optimized to initiate the desired carbon-carbon bond formation. Putting this into context with the recently emerging concept of flow chemistry, which brings several practical advantages to the application of laser pulses, we want to encourage experimental groups to exploit this concept. Another path was opened by several additions to the commonly used laser pulse optimization algorithm (optimal control theory, OCT), several of which were developed in our group. The OCT algorithm as such is a purely mathematical optimization procedure, with no direct relation to experimental requirements. This means that usually the electric fields obtained out of OCT optimizations do not resemble laser pulses that can be achieved experimentally. However, the previously mentioned additions are aimed at closing the gap toward the experiment. In a recent quantum control study of our group, these algorithmic developments came to fruition. We were able to suggest a shaped laser pulse which can induce a long-living wave packet in the excited state of uracil. This might pave the way for novel experiments dedicated to investigating the formation of biological photodamage in DNA and RNA. The pulse we suggest is surprisingly simple because of the extended OCT algorithm and fulfills all criteria to be experimentally accessible.

Nickel‐Catalyzed Enantioconvergent Borylation of Racemic Secondary Benzylic Electrophiles

AbstractNickel‐catalyzed cross‐coupling has emerged as the most versatile approach to date for achieving enantioconvergent carbon–carbon bond formation using racemic alkyl halides as electrophiles. In contrast, there have not yet been reports of the application of chiral nickel catalysts to the corresponding reactions with heteroatom nucleophiles to produce carbon–heteroatom bonds with good enantioselectivity. Herein, we establish that a chiral nickel/pybox catalyst can borylate racemic secondary benzylic chlorides to provide enantioenriched benzylic boronic esters, a highly useful family of compounds in organic synthesis. The method displays good functional group compatibility (e.g., being unimpeded by the presence of an indole, a ketone, a tertiary amine, or an unactivated alkyl bromide), and both of the catalyst components (NiCl2⋅glyme and the pybox ligand) are commercially available.

Gold(I)-Catalyzed Oxidative Cascade Cyclization of 1,4-Diyn-3-ones for the Construction of Tropone-Fused Furan Scaffolds.

Gold(I)-catalyzed cascade cyclization of 1,4-diyn-3-ones with a pyridine N-oxide enabled direct construction of a benzo[6,7]cyclohepta[1,2- b]furan scaffold with the formation of four bonds. This reaction would proceed through oxidative cyclization, alkynyl migration, and 5- endo-dig type cyclization. Synthesis of benzotropone-fused naphtho[1,2- b]furans through a two-step sequence, including epoxidation and In(OTf)3-catalyzed intramolecular carbon-carbon bond formation, is also presented.

Visible‐Light‐Induced Nickel‐Catalyzed Negishi Cross‐Couplings by Exogenous‐Photosensitizer‐Free Photocatalysis

AbstractThe merging of photoredox and transition‐metal catalysis has become one of the most attractive approaches for carbon–carbon bond formation. Such reactions require the use of two organo‐transition‐metal species, one of which acts as a photosensitizer and the other one as a cross‐coupling catalyst. We report herein an exogenous‐photosensitizer‐free photocatalytic process for the formation of carbon–carbon bonds by direct acceleration of the well‐known nickel‐catalyzed Negishi cross‐coupling that is based on the use of two naturally abundant metals. This finding will open new avenues in cross‐coupling chemistry that involve the direct visible‐light absorption of organometallic catalytic complexes.

Application of the Cation Pool Method for Fluorination and No-Carrier-Added Radio-Fluorination

In 1999 Yoshida and co-workers developed the cation pool method which stabilized carbamate cationic intermediates generated during a two electron oxidation followed by deprotonation that takes place in the anodic compartment of a two compartment cell under low temperatures.1 The method allows for rapid reactions with nucleophiles that may be unstable during electrolysis and can be added to the reaction mixture at the end of electrolysis to form the final product. Here, we report on the extension of the cation pool method for the application of electrochemical fluorination and radio-fluorination of methyl (phenylthio)acetate. Electrochemical fluorination and no-carrier-added radio-fluorination were successfully achieved using the cation pool method . Figure 1 shows the schematic of no-carrier-added electrochemical radio-fluorination of methyl (phenylthio)acetate using cation pool method. The cation pool method has tremendous potential for radiofluorination experiments. The excess concentration of cations may provide an efficient reaction mechanism for late-stage fluorination under low fluoride concentrations encountered in radiochemistry. Furthermore, radiochemical yield, which is reduced by decay of the radioisotope, can benefit from a rapid late-stage fluorination reaction. The cation pool can be prepared prior to cyclotron production of 18F isotope, thereby, providing a rapid late-stage fluorination reaction, maximizing radiochemical yield by minimizing decay through a rapid reaction of the previously prepared cations with 18F-fluoride. Synthesis parameters such as temperature, supporting electrolyte concentration and type, and precursor concentration were studied and optimized. The fluorination and radiofluorination yields of 12% and 6.7% were obtained, respectively, using the optimum conditions. The products were characterized using gas chromatography–mass spectrometry (GC-MS), nuclear magnetic resonance (NMR), radio-thin-layer chromatography (radio-TLC) and high-performance liquid chromatography (HPLC). This method can also be applied for a late-stage no-carrier-added radiofluorination to develop new positron emission tomography (PET) tracers. Figure 1. Schematic of no-carrier-added electrochemical 18F-fluorination of methyl (phenylthio)acetate using cation pool method. References Yoshida, J. et al. Direct Oxidative Carbon−Carbon Bond Formation Using the “Cation Pool” Method. 1. Generation of Iminium Cation Pools and Their Reaction with Carbon Nucleophiles. J. Am. Chem. Soc. 121, 9546–9549 (1999). Figure 1

Umpolung Diels-Alder Reactions By Electrocatalysis

Although the Diels–Alder reaction is a classic reaction, it is still at the forefront of the carbon–carbon bond formation toolbox in synthetic chemistry. In particular, the mechanism of the reaction has been well studied, and the scope has been expanded to a wide variety of diene/dienophile combinations. However, electronic matching needs to be considered; more specifically, that one reaction partners should be electron-rich and the other electron-deficient. To overcome this hurdle, "umpolung" strategy has been proven to be powerful approach. In this context, single electron transfer (SET) would be the most simple and straightforward process. For example, electron-deficient radical cation species can be produced from electron-rich reactant via SET oxidation. A typical example of the umpolung Diels-Alder reactions is the reaction between an electron-rich diene and a dienophile. These combinations are electronically mismatched, however, SET oxidation can produce a radical cation of one component, which is then able to be trapped by the other component. In addition to the use of chemical redox agents, photocatalysis and electrocatalysis are currently recognized as effective approaches to induce SET processes. Umpolung Diels-Alder reactions have also been extensively studied for almost half a century, however, scope of the reactions has been limited. In many cases, the reactions were triggered by SET oxidation of diene components, generating the radical cation species, and which were then trapped by dienophiles. In 2011, Yoon elegantly demonstrated the opposite version, namely, the reaction triggered by SET oxidation of dienophile components using photocatalysis. We have been developing carbon-carbon bond formations by electrocatalysis in lithium perchlorate (LiClO4)/nitromethane (CH3NO2) electrolyte solution.1 In most cases, the use of LiClO4/CH3NO2 electrolyte solution is critical, which exhibits remarkable property as a Lewis acid to facilitate the reactions of carbon-centered radical cations with carbon nucleophiles. We also have shown that the electrocatalysis in LiClO4/CH3NO2 electrolyte solution is effective to induce umpolung Diels-Alder reactions.2 In this talk, recent advancement of the umpolung Diels-Alder reactions by electrocatalysis will be discussed in details. (1) Imada, Y.; Yamaguchi, Y.; Shida, N.; Okada, Y.; Chiba, K. Chem. Commun. 2017, 53, 3960–3963.(2) (a) Ozaki, A.; Yamaguchi, Y.; Okada, Y.; Chiba, K. ChemElectroChem 2017, 4, 1852–1855. (b) Okada, Y.; Yamaguchi, Y.; Ozaki, A.; Chiba, K. Chem. Sci. 2016, 7, 6387–6393. Figure 1

Visible‐Light‐Promoted Copper‐Catalyzed Regioselective Benzylation of Pyridine N‐Oxides versus Thermal Acylation Reaction with Toluene Derivatives

Copper‐catalyzed visible light mediated direct C–H bond benzylation of pyridine N‐oxides with toluene derivatives was accomplished by recent developments in photochemical carbon–carbon bond formation through a photo‐induced bond‐dissociation strategy. This visible light driven protocol has been successfully applied to a broad scope of pyridine N‐oxides and toluene derivatives. Furthermore, preliminary research indicates that the acylation reaction can be carried out under thermal reaction conditions. This protocol provides easy access to 2‐benzyl and 2‐acyl pyridine N‐oxide derivatives in the presence of a copper catalyst.

The Concept of "Noble, Heteroatom-Doped Carbons," Their Directed Synthesis by Electronic Band Control of Carbonization, and Applications in Catalysis and Energy Materials.

Carbonization of organic compounds with a highest occupied molecular orbital (HOMO) level more positive than 1.3 V practically automatically results in highly sp2 -conjugated, heteroatom-doped carbons. Due to the stability of the starting compounds, carbon bond formation is restricted to result in morphologies with a surprisingly high local order which as such are noble, i.e., they are hard to oxidize and combust. The work function of electrons in these systems is so positive that the systems usually accept electrons, i.e., they oxidize other matter rather than being oxidized. Such noble, heteroatom-doped carbons have been proven to be efficient, metal-free electrocatalysts, but can be also beneficially used in the manufacturing of carbon nanomaterials for energy applications or as highly active, non-innocent catalytic supports.

Radical Anions from Urea‐type Carbonyls: Radical Cyclizations and Cyclization Cascades

AbstractRadical anions generated from urea carbonyls by reductive electron transfer are exploited in carbon–carbon bond formation. New radical cyclizations of urea radical anions deliver complex nitrogen heterocycles and, depending upon the proton source used in the reactions, a chemoselective switch between reaction pathways can deliver two heterobicyclic scaffolds. A computational study has been used to investigate the selectivity of the urea radical processes. Furthermore, radical cyclization cascades involving urea radical anions deliver unusual spirocyclic aminal architectures.