Ketyl Radical Research Articles

Green Metal‐Free Photochemical Hydroacylation of Unactivated Olefins

AbstractDirect alkylation of C(sp2)−H bonds to convert an aldehyde into a ketone is a notorious transformation, due to the laborious challenge of the formation of ketyl or acyl radicals. Herein, we report a green, cheap, metal‐free and efficient method for the hydroacylation of olefins in water. This photochemical protocol utilizes phenylglyoxylic acid, a commercially available small organic molecule, as the photoinitiator, water as the solvent and household fluorescent lamps as the irradiation source, leading to a broad substrate scope of products in moderate to good yields. A wide range of aromatic and aliphatic aldehydes, terminal and non‐terminal alkenes and pharmaceutically relevant molecules can be employed, without the need of directing groups and additives or metal catalysts.

Ketyl-phenoxyl triplet radical pair in glycerol: Magnetic field effect and cage kinetics in terms of the two-state model.

The geminate recombination kinetics of the triplet pairs of neutral radicals formed as a result of hydrogen atom transfer from 4-methylphenol to 4,4'-dimethylbenzophenone in the triplet excited state was studied by laser flash photolysis in the temperature range of 263-323 K. The pair included aromatic ketyl and 4-methylphenoxyl radicals produced in a viscous (∼10 P) solution of the initial reagents in glycerol. The geminate recombination kinetics demonstrate a "tail" c(t) ∼ 1/t, with contribution of magnitude An, which increases with temperature. The two-state (TS) model, which takes into account the potential well caused by the interaction between radicals at short distances and the radicals that escaped from a well but returned to it after free diffusion outside the well, was used to fit the data. The application of an external magnetic field (MF) (0.2 T) gave rise to the retardation of the geminate recombination and to the increase of fraction of radicals in the solvent bulk. The bell-shaped dependence of the magnetic field effect (MFE) value upon temperature (with a maximum near 300 K) was found. This dependence correlates with An and its dependence on the MF. At temperatures lower than 270 K, both the contribution of the nonexponential part of geminate recombination kinetics and the MFE were found to be small. The TS model can quantitatively describe the effects of solvent viscosity and MF on the kinetics of geminate recombination of triplet RP.

Bromide-Promoted Visible-Light-Induced Reductive Minisci Reaction with Aldehydes

Radical addition is a robust tool for bond formation. While ketyl radical reactivity of aldehydes by photoredox has been well-established, herein, we have now revealed a pathway for umpolung additi...

Dual Benzophenone/Copper-Photocatalyzed Giese-Type Alkylation of C(sp3 )-H Bonds.

Photocatalyzed Giese-type alkylations of C(sp3 )-H bonds are very attractive reactions in the context of atom-economy in C-C bond formation. The main limitation of such reactions is that when using highly polymerizable olefin acceptors, such as unsubstituted acrylates, acrylonitrile, or methyl vinyl ketone, radical polymerization often becomes the dominant or exclusive reaction pathway. Herein, we report that the polymerization of such olefins is strongly limited or suppressed when combining the photocatalytic activity of benzophenone (BP) with a catalytic amount of Cu(OAc)2 . Under mild and operationally simple conditions, the Giese adducts resulting from the C(sp3 )-H functionalization of amines, alcohols, ethers, and cycloalkanes could be synthesized. Preliminary mechanistic studies have revealed that the reaction does not proceed through a radical chain, but through a dual BP/Cu photocatalytic process, in which both CuII and low-valent CuI/0 species, generated in situ by reduction by the BP ketyl radical, may react with α-keto or α-cyano intermediate radicals, thus preventing polymerization.

One-Step Photochemical Green Synthesis of Water-Dispersible Ag, Au, and Au@Ag Core-Shell Nanoparticles.

A simple and green synthetic protocol for the rapid and effective preparation of Ag, Au and Au@Ag core-shell nanoparticles (NPs) is reported based on the light irradiation of a biocompatible, water-soluble dextran functionalized with benzophenone (BP) in the presence of AgNO3 , HAuCl4 , or both. Photoactivation of the BP moiety produces the highly reducing ketyl radicals through fast (<50 ns) intramolecular H-abstraction from the dextran scaffold, which, in turn, ensures excellent dispersibility of the obtained metal NPs in water. The antibacterial activity of the AgNPs and the photothermal action of the Au@Ag core-shell are also shown.

Hydrogen Abstraction of Ketoprofen in the Excited Triplet State with Indole and Methylindoles.

Relaxation of excited states and reactivity of ketoprofen (KP), one of the most popular nonsteroidal anti-inflammatory drugs, with indole and methylindoles have been studied with transient absorption and quantum chemical calculations. KP in the excited triplet state, 3KP*, abstracted a hydrogen atom from indole and methylindoles to afford a ketyl radical and a counter radical. The bimolecular quenching rate constants of 3KP* by indole and methylindoles, kq, and the hydrogen atom abstraction rate constants, kr, were obtained. The kr values for methylindoles were larger than that for indole; in addition, transient spectra at around 350 nm, assigned to the corresponding C-centered radical, was observed. These results indicate that 3KP* abstracts a hydrogen atom of the methyl group as well as that of N-H in the indole frame. These findings give us information on the reactivity of excited KP in the vicinity of tryptophan in a KP-protein complex, which will ultimately cause photosensitization on human skin.

Production of Singlet Oxygen (1O2) during the Photochemistry of Aqueous Pyruvic Acid: The Effects of pH and Photon Flux under Steady-State O2(aq) Concentration

The photochemistry of pyruvic acid (PA) in aqueous atmospheric particles contributes to the production of secondary organic aerosols. This work investigates the fate of ketyl and acetyl radicals produced during the photolysis (λ ≥ 305 nm) of 5-100 mM PA under steady state [O2(aq)] = 260 μM (1.0 ≤ pH ≤ 4.5) for photon fluxes between 1 and 10 suns. The radicals diffuse quickly into the water/air interface of microbubbles and react with dissolved O2 to produce singlet oxygen (1O2*). Furfuryl alcohol is used to trap and bracket the steady-state production of 2 × 10-12 ≤ [1O2*] ≤ 1 × 10-11 M. Ion chromatography mass spectrometry shows that 2,3-dimethyltartaric acid (DMTA), 2-(3-oxobutan-2-yloxy)-2-hydroxypropanoic acid (oxo-C7 product), and 2-(1-carboxy-1-hydroxyethoxy)-2-methyl-3-oxobutanoic acid (oxo-C8 product) are formed under all conditions investigated. The sigmoidal dependence of initial reaction rates with pH resembles the dissociation curve of PA. For increasing photon fluxes, the branching ratio of products shifts away from the radical recombination that favors DMTA toward multistep radical chemistry forming more complex oxocarboxylic acids (oxo-C7 + oxo-C8). The large steady-state production of 1O2 indicates that PA in aerosols can be a significant source of atmospheric oxidants on par with natural organic matter.

Effect of ketyl radical on the structure and performance of holographic polymer/liquid-crystal composites

Holographic polymer/liquid-crystal composites, which are periodically ordered materials with alternative polymer-rich and liquid-crystal-rich phases, have drawn increasing interest due to their unique capabilities of reconstructing colored three-dimensional (3D) images and enabling the electro-optic response. They are formed via photopolymerization induced phase separation upon exposure to laser interference patterns, where a fast photopolymerization is required to facilitate the holographic patterning. Yet, the fast photopolymerization generally leads to depressed phase separation and it remains challenging to boost the holographic performance via kinetics control. Herein, we disclose that the ketyl radical inhibition is able to significantly boost the phase separation and holographic performance by preventing the proliferated diffusion of initiating radicals from the constructive to the destructive regions. Dramatically depressed phase separation is caused when converting the inhibiting ketyl radical to a new initiating radical, indicating the significance of ketyl radical inhibition when designing high performance holographic polymer composites.

Visible-Light Photoredox Enables Ketone Carbonyl Alkylation for Easy Access to Tertiary Alcohols

Being a handle for synthesizing quaternary carbon centers and olefins, together with ubiquitous appearance in organic building blocks, makes tertiary alcohols valuable targets in synthesis. However, traditional syntheses of these alcohols have faced several challenges including the employment of functionalized reactive reagents, undesirable side reactions, and decomposition of the alcohol products under harsh conditions. The paucity of a synthetic approach to bulky tertiary alcohols prompts our interest to develop a benign catalytic protocol to tackle the current issues. Here, we have successfully demonstrated the use of ketyl radicals in intermolecular cross radical–radical coupling, which has opened a different door for accessing complex tertiary alcohols. On the other hand, by starting from feedstock and naturally derived chemicals without any pre-activation, it would be superior to traditional methodologies in the industrial context.

Photoinduced intermolecular charge transfer processes on pure and modified silica surfaces

This article briefly reviews some of our work over the past two decades devoted to the photoinduced electron-transfer processes and formation of bimolecular complexes–exiplexes between adsorbed donor pyrene and anthracene and acceptor N,N-dimethylaniline molecules on silica and silica–titania surfaces. Quenching of the fluorescence of acenes by N,N-dimethylaniline on silica surfaces is found to be diffusion controlled and results from exciplex formation at room temperature. The effect of silica–titania on the processes of photoinduced electron-transfer resulted vise-versa in increases of the fluorescence intensity from the adsorbed acenes. This phenomenon is explained by the selective adsorption of N,N-dimethylaniline on the acid “titanium” centers and a shift of the acenes to weaker adsorption sites located on the silica support. The excited molecular pair effectively yields reduced titanium ions due to an electron transfer process. This study demonstrates the important role that adsorption of organic molecules plays in photocatalytic processes on the surface of semiconductor composites. Sol–gel produced porous silica modified with benzophenone molecules leads to full photoreduction of silver and gold ions. Formation of stable Ag and Au nanoparticles embedded in porous silica films was carried out by irradiation of silver (gold) ions-modified silica in benzophenone–water–isopropanol solution. The triplet state of benzophenone takes part in the formation of the reducing agents, such as ketyl radicals and anion radicals of benzophenone and isopropanol. These systems can be used as bactericide materials, for extraction of metal ions from solution, for photocatalytic reduction of toxic transition metals and other applications.

Photoenzymatic Catalysis Enables Radical‐Mediated Ketone Reduction in Ene‐Reductases

AbstractFlavin‐dependent ene‐reductases (EREDs) are known to stereoselectively reduce activated alkenes, but are inactive toward carbonyls. Demonstrated here is that in the presence of photoredox catalysts, these enzymes will reduce aromatic ketones. Mechanistic experiments suggest this reaction proceeds through ketyl radical formation, a reaction pathway that is distinct from the native hydride‐transfer mechanism. Furthermore, this reactivity is accessible without modification of either the enzyme or cofactors, allowing both native and non‐natural mechanisms to occur simultaneously. Based on control experiments, we hypothesize that binding to the enzyme active site attenuates the reduction potential of the substrate, enabling single‐electron reduction. This reactivity highlights opportunities to access new catalytic manifolds by merging photoredox catalysis with biocatalysis.

Photoenzymatic Catalysis Enables Radical-Mediated Ketone Reduction in Ene-Reductases.

Flavin-dependent ene-reductases (EREDs) are known to stereoselectively reduce activated alkenes, but are inactive toward carbonyls. Demonstrated here is that in the presence of photoredox catalysts, these enzymes will reduce aromatic ketones. Mechanistic experiments suggest this reaction proceeds through ketyl radical formation, a reaction pathway that is distinct from the native hydride-transfer mechanism. Furthermore, this reactivity is accessible without modification of either the enzyme or cofactors, allowing both native and non-natural mechanisms to occur simultaneously. Based on control experiments, we hypothesize that binding to the enzyme active site attenuates the reduction potential of the substrate, enabling single-electron reduction. This reactivity highlights opportunities to access new catalytic manifolds by merging photoredox catalysis with biocatalysis.

Separation of Re(VII) from aqueous solution by acetone-enhanced photoreduction: an insight into the role of acetone

Efficient separation of rhenium (Re) from aqueous solution is pivotal in the resource recovery, and suitable to simulate the elimination of radiotoxic technetium (Tc) due to their similar properties. In this work, we achieved a high Re(VII) separation ratio of 95.2% within 30 min from aqueous solution via an acetone-enhanced photoreduction method, in which soluble ReO4− was reduced to insoluble ReOx and Re(0) in the presence of acetone and isopropanol. Compared with the situation in absence of acetone, acetone absorbed most of the UV energy, and the produced triplet acetone could abstract Hα atoms from isopropanol to form more strongly reductive ketyl radicals, leading to the enhancement in photoreduction. Isopropanol was the most qualified for Re(VII) photoredction due to its low C–Hα bond energy. The addition of alkali also benefited the Re(VII) separation by eliminating produced protons, and stabilizing the intermediate Re(VI) to preventing the re-formation of Re(VII) through disproportionation of Re(VI). Furthermore, selective and effective separation of Re(VII) from simulated high level liquid waste containg Nd(III) was realized as well. This work gains an insight into the role of acetone in the enhanced Re(VII) photoreduction, which may be of great significance in developing novel approaches for hydrometallurgy and spent nuclear fuel reprocessing.

The Effects of Reactant Concentration and Air Flow Rate in the Consumption of Dissolved O₂ during the Photochemistry of Aqueous Pyruvic Acid.

The sunlight photochemistry of the organic chromophore pyruvic acid (PA) in water generates ketyl and acetyl radicals that contribute to the production and processing of atmospheric aerosols. The photochemical mechanism is highly sensitive to dissolved oxygen content, [O2(aq)], among other environmental conditions. Thus, herein we investigate the photolysis (λ ≥ 305 nm) of 10–200 mM PA at pH 1.0 in water covering the relevant range 0 ≤ [O2(aq)] ≤ 1.3 mM. The rapid consumption of dissolved oxygen by the intermediate photolytic radicals is monitored in real time with a dissolved oxygen electrode. In addition, the rate of O2(aq) consumption is studied at air flow rates from 30.0 to 900.0 mL min−1. For the range of [PA]0 covered under air saturated conditions and 30 mL min−1 flow of air in this setup, the estimated half-lives of O2(aq) consumed by the photolytic radicals fall within the interval from 22 to 3 min. Therefore, the corresponding depths of penetration of O2(g) into water (x = 4.3 and 1.6 µm) are determined, suggesting that accumulation and small coarse mode aqueous particles should not be O2-depleted in the presence of sunlight photons impinging this kind of chromophore. These photochemical results are of major tropospheric relevance for understanding the formation and growth of secondary organic aerosol.

Preparation of Ni(cod)2 Using Light as the Source of Energy

A convenient method to prepare Ni(cod)2 from Ni(acac)2 using light as the source of energy is reported. In the first step of this process, xanthone is reductively dimerized upon irradiation of solar or LED light in 2-propanol to form a vicinal diol possessing a highly sterically congested C–C bond. In the second step, a ketyl radical derived from the diol reacts with Ni(acac)2, ultimately reducing nickel(II) to nickel(0), which is bound by 1,5-cyclooctadiene (COD) to produce Ni(cod)2. This new method obviates the need for hazardous reductants such as diisobutylaluminum hydride (DIBAH) and sodium.

Time-Resolved Spectroscopic Observation and Characterization of Water-Assisted Photoredox Reactions of Selected Aromatic Carbonyl Compounds.

In recent years, unusual and efficient self-photoredox reactions were detected for selected benzophenone derivatives (BPs) and anthraquinone derivatives (AQs) in aqueous environments by Wan and co-workers, where the carbonyl undergoes reduction to the corresponding alcohol and a side-chain alcohol group undergoes oxidation to the corresponding carbonyl. To unravel the photoredox reaction mechanisms of these types of BPs and AQs in aqueous environments, we have utilized a combination of time-resolved spectroscopy techniques such as femtosecond transient absorption, nanosecond transient absorption, and nanosecond time-resolved resonance Raman spectroscopy to detect and characterize the electronic absorption and vibrational spectra of the intermediates and transient species from the femtosecond to microsecond time region after they are generated in the photoredox reactions. With the assistance of density functional theory calculations to simulate the electronic absorption and Raman spectra, the structural and kinetic information on the key reactive intermediates is described. Furthermore, the reaction pathways were calculated by finding the transition states connecting with the reactant and product complexes to better understand the photoredox reaction mechanism. In this Account, we summarize some of our time-resolved spectroscopic observations and characterization of water-assisted photoredox reactions of selected BPs and AQs. In the strong hydrogen-donor solvent isopropanol, the commonly studied photoreduction reaction for aromatic carbonyls via an intermolecular hydrogen atom tranfer process was observed for BPs and AQs. The photoredox reactions for the investigated BPs and AQs in aqueous environments occur on the triplet excited-state surface. Under moderately acidic aqueous conditions, the photoredox reactions for BPs and AQs are triggered by a proton transfer (PT) pathway. In neutral aqueous solutions, AQs may also undergo proton-coupled electron transfer (PCET) leading to the photoredox reaction, while BPs generate the ketyl radical species. Both BPs and AQs prefer the photohydration reaction in high-proton-concentration aqueous solutions (pH 0). The PT and PCET processes were found to offer more possibilities for the aromatic carbonyl compounds to lead to new photochemical reactions like the unusual photoredox reactions associated with BPs and AQs described here. Clear characterization of the photophysical pathways and the photochemical reactions of representative aromatic carbonyl compounds in aqueous environments not only provides fundamental information to better understand the photochemistry of carbonyl-containing compounds but also will facilitate the development of applications of these systems, like photochemical synthesis, drugs, and photolabile protecting groups. In addition, the importance of water molecules in the photochemical reactions of interest here may also lead to further understanding of how water influences the photochemistry of related carbonyl-containing compounds in aqueous environments.

Preparation of single chain nanoparticles via photoinduced radical coupling process

This contribution introduces a straightforward method for preparing well-defined polymeric nanoparticles using radical coupling process of ketyl moieties resulted from triplet excitation of pendant benzophenone groups. In the first step, poly(styrene-co-chloromethylstyrene) is synthesized by thermally initiated controlled radical copolymerization technique and subsequently, pendant chloride groups undergo post-modification with 4–hydroxybenzophenone. Achieved well-defined side–chain benzophenone containing copolymers generate ketyl radicals in the presence of excess hydrogen donor molecule upon UV-light irradiation and intramolecularly crosslinked nanoparticles are formed by radical coupling process in dilute regime. Resulting single chain nanoparticles and intermediates are characterized by 1H NMR, gel permeation chromatography, differential scanning calorimetry, UV–Vis spectrometry and electron microscopy techniques.

Photochemical preparation of gold nanoparticle decorated cyclodextrin vesicles with tailored plasmonic properties.

We report a photochemical strategy for the preparation of plasmonic vesicles by the in situ formation of gold nanoparticles at the surface of cyclodextrin host vesicle templates decorated with photoactive guest polymers. Upon irradiation with UV light, these carefully designed polymer shells undergo a Norrish type I reaction to generate reducing radicals for the in situ reduction of gold salts and simultaneously provide a stabilizing matrix allowing for a dense decoration with discrete gold seeds. In a highly controlled growth procedure the gold particle size can be adjusted between 3 and 28 nm resulting in an increasing interparticle plasmonic coupling as revealed by a pronounced redshift of the surface plasmon resonance (SPR) band and an enhanced absorption at wavelengths above 600 nm. This unique combination of cyclodextrin vesicles capable of specifically recognizing guest molecules with a plasmonic particle shell displaying multiple interparticle gaps acting as electromagnetic hotspots shows great potential for surface-enhanced Raman scattering (SERS) applications.

The role of ketyl radicals in free radical photopolymerization: new experimental and theoretical insights

In this work, the role of ketyl radicals produced by the abstraction of a hydrogen from an amine by a thioxanthone-based photoinitiator is considered within the scope of the free radical photopolymerization process.

Competition of singlet and triplet recombination of radical pairs in photoreactions of carboxy benzophenones and aromatic amino acids.

Time-resolved chemically induced dynamic nuclear polarization (CIDNP) and transient absorption (TA) were applied to reveal the branching ratio of the singlet and triplet recombination channels in the reaction of short-lived radicals of carboxy benzophenones and the aromatic amino acids histidine, tryptophan, and tyrosine in neutral aqueous solution. It was established that the share of triplet recombination increases with increasing number of carboxylic groups: no triplet recombination was found for 4-carboxy benzophenone, whereas ∼13% of radicals of 4,4'-dicarboxy benzophenone (DCBP) and ∼27% of radicals of 3,3',4,4'-tetracarboxy benzophenone (TCBP) react with histidine radicals from the triplet state of radical pairs. The main idea is that the protonated (π,π*) triplet state of TCBP or DCBP is populated via back electron transfer from the ketyl radical of TCBP or DCBP to the radical of the amino acid. The protonated triplet state of the ketone decays with the formation of a metastable hydroxylated product, which is detected by TA. Taking into account triplet recombination provides excellent coincidence between experimental data and the simulated CIDNP kinetics.