Photocatalytic Conversion of Benzyl Alcohols/Methyl Arenes to Aryl Nitriles via H-Abstraction by Azide Radical

This report presents the visible-light-assisted synthesis of aryl nitriles from easily accessible alcohols or methyl arenes in the presence of O₂. Organic photoredox catalyst, 4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene), induces single electron transfer (SET) from azide N₃⁻ and generates azide radical N₃⋅.The photogenerated N₃⋅ abstracts H atom from α-C−H bond of benzylic system, which provides aldehyde and hydrazoic acid (HN₃) in situ. This reaction subsequently forms azido alcohol intermediate that transforms into nitrile with the assistance of triflic acid (Brønsted acid). A range of alcohols and methyl arenes successfully underwent cyanation at room temperature with good to excellent yields and showed good functional group tolerance.     

Electrochemically Driven C−H Hydrogen Abstraction Processes with the Tetrachloro‐Phthalimido‐N‐Oxyl (Cl4PINO) Catalyst

The radical redox mediator tetrachloro‐phthalimido‐N‐oxyl (Cl₄PINO) is generated at a glassy carbon electrode and investigated for the model oxidation of primary and secondary alcohols with particular attention to reaction rates and mechanism. The two‐electron oxidation reactions of a range of primary, secondary, and cyclic alcohols are dissected into an initial step based on C−H hydrogen abstraction (rate constant k₁, confirmed by kinetic isotope effect) and a fast radical‐radical coupling of the resulting alcohol radical with Cl₄PINO to give a ketal that only slowly releases the aldehyde/ketone and redox mediator precursor back into solution (rate constant k₂). In situ electrochemical EPR reveals Cl₄PINO sensitivity towards moisture. DFT methods are applied to confirm and predict C−H hydrogen abstraction reactivity.     

Kinetic and Product Study of the S-oxidation vs HAT Chemoselectivity in Reactions Promoted by Nonheme Iron(IV)-oxo Complex/NHPI Mediator System

The chemoselectivity between S-oxidation and hydrogen atom transfer (HAT) from C−H bonds has been investigated in the oxidations of a series of aryl sulfides, alkyl aromatic compounds and benzylic alcohols promoted by the iron(IV)-oxo complex [(N4Py)Fe^IV(O)]²⁺ (N4Py: N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)-methylamine) either alone or in the presence of the N-hydroxyphthalimide (NHPI) mediator via kinetic and product studies. Kinetic analyses indicate a generally higher reactivity of [(N4Py)Fe^IV(O)]²⁺ for S-oxidation process while HAT is favored in the reactions promoted by phthalimide-N-oxyl radical (PINO) deriving from NHPI oxidation. Product analysis in intermolecular competitive oxidations confirms the kinetic results with sulfoxides obtained as major products in the oxidation promoted by [(N4Py)Fe^IV(O)]²⁺. Conversely, when NHPI is employed as a mediator, significant differences in terms of chemoselectivity are observed, and HAT-derived products are obtained in higher yields which translate into an inversion of selectivity in the case of the substrates containing activated C−H bonds like diphenylmethane, triphenylmethane and benzylic alcohols. A similar change of chemoselectivity is also observed in the oxidation of aromatic substrates containing both a sulfur atom and α to OH benzylic C−H bonds, with the sulfoxide product more abundant in the absence of NHPI and carbonyl products prevailing with the [(N4Py)Fe^IV(O)]²⁺/NHPI system.     

Amine-Free,Directing-Group-Free and Redox-Neutral α-Alkylation of Saturated Cyclic Ketones

The activation of the α-C−H bond of ketones typically requires an amine and a directing group to guide the reaction selectivity in amine-catalysis carbonyl chemistry. For an α-C−H bond activation of ketone, directing groups are also required to control the reaction selectivity. Reported herein is the first α-alkylation of cyclic ketones in the absence of an amine catalyst and directing group. ¹H NMR, XPS, EPR studies and DFT calculations indicate that an α-carbon radical intermediate is formed through direct and selective activation of the inert α-C−H bond of ketones chelating on the surface of colloidal quantum dots (QDs). Such an interaction is essential for weakening the C−H bond, as exemplified, using CdSe QDs as the sole photocatalyst to execute α-C−H alkylation of cyclic ketones under visible-light irradiation. Without an amine catalyst and directing group, the high step- and atom-economy transformation under redox-neutral condition opens a new way for α-C−H functionalization of ketones in carbonyl chemistry.     

Visible Light-Enabled sp3-C−H Functionalization with Chloro- and Bromoalkynes: Chemoselective Route to Vinylchlorides or Alkynes

An unprecedented direct atom-economic chemo- and regioselective hydroalkylation of chloroalkynes and an sp³-C−H alkynylation of bromoalkynes was achieved. The reaction partners are unfunctionalized ethers, alcohols, amides, and even non-activated hydrocarbons. We found that a household fluorescent bulb was able to excite a diaryl ketone, which then selectively abstracts a H-atom from an sp³-C−H bond. The product of a formal alkyne insertion into the sp³-C−H bond was obtained with chloroalkynes, providing valuable vinyl chlorides. The photo-organocatalytic hydrogen atom transfer strategy gives rise to a broad range of diversely functionalized olefins. When bromoalkynes are applied in the presence of a base, a chemoselectivity switch to an alkynylation is observed. This reaction can even be performed for the alkynylation of unactivated sp³-C−H bonds, in this case with a preference of the more substituted carbon. Accompanying quantum chemical calculations indicate a vinyl radical intermediate with pronounced linear coordination of the carbon radical center, thus enabling the formation of both diastereoisomers after H-atom abstraction, suggesting that the (Z)-diastereoisomer is preferred, which supports the experimentally observed (E/Z)-distribution.     

Photocatalytic Dehydrogenative Cross‐Coupling of Alkenes with Alcohols or Azoles without External Oxidant

Direct cross‐coupling between alkenes/R‐H or alkenes/RXH is a dream reaction, especially without external oxidants. Inputting energy by photocatalysis and employing a cobalt catalyst as a two‐electron acceptor, a direct C−H/X−H cross‐coupling with H₂ evolution has been achieved for C−O and C−N bond formation. A new radical alkenylation using alkene as the redox compound is presented. A wide range of aliphatic alcohols—even long chain alcohols—are tolerated well in this system, providing a new route to multi‐substituted enol ether derivatives using simple alkenes. Additionally, this protocol can also be used for N ‐vinylazole synthesis. Mechanistic insights reveal that the cobalt catalyst oxidizes the photocatalyst to revive the photocatalytic cycle.     

Photocatalysis with Quantum Dots and Visible Light: Selective and Efficient Oxidation of Alcohols to Carbonyl Compounds through a Radical Relay Process in Water

Selective oxidation of alcohols to aldehydes/ketones has been achieved with the help of 3‐mercaptopropionic acid (MPA)‐capped CdSe quantum dot (MPA‐CdSe QD) and visible light. Visible‐light‐prompted electron‐transfer reaction initiates the oxidation. The thiyl radical generated from the thiolate anion adsorbed on a CdSe QD plays a key role by abstracting the hydrogen atom from the C−H bond of the alcohol (R¹CH(OH)R²). The reaction shows high efficiency, good functional group tolerance, and high site‐selectivity in polyhydroxy compounds. The generality and selectivity reported here offer a new opportunity for further applications of QDs in organic transformations.     

Dinicotinamidium squarate

The crystal structure determination of the dinicotinamidium squarate salt, 2C₆H₇N₂O⁺·C₄O₄²⁻, is reported, with the squarate dianion residing on an inversion centre and the unique cation in a general position. Salt formation occurs by donation of two H atoms from squaric acid to the nicotin­amide base. The crystal packing is derived from three types of hydrogen bonding. The primary hydrogen bond involves a squarate anion O atom and an H atom of the protonated pyridine group of the nicotin­amide, with an N⋯O distance of 2.5760 (13) Å. The second hydrogen bond involves a second anion O atom and an amide H atom, with an N⋯O distance of 2.8374 (14) Å. Thirdly, an intermolecular interaction between two coplanar nicotin­amide moieties occurs between an amide O atom and a symmetry‐related amide H atom, with an N1⋯O3 distance of 2.8911 (15) Å. These hydrogen bonds are also responsible for the planarity of the nicotin­amide moiety in the salt.     

Catalytic Ammonia Oxidation to Dinitrogen by a Nickel Complex

We report a nickel complex for catalytic oxidation of ammonia to dinitrogen under ambient conditions. Using the aryloxyl radical 2,4,6-tri-tert-butylphenoxyl (^tBu₃ArO⋅) as a H atom acceptor to cleave the N−H bond of a coordinated NH₃ ligand up to 56 equiv of N₂ per Ni center can be generated. Employing the N-oxyl radical 2,2,6,6-(tetramethylpiperidin-1-yl)oxyl (TEMPO⋅) as the H-atom acceptor, up to 15 equiv of N₂ per Ni center are formed. A bridging Ni-hydrazine product identified by isotopic nitrogen (¹⁵N) studies and supported by computational models indicates the N−N bond forming step occurs by bimetallic homocoupling of two paramagnetic [Ni]−NH₂ fragments. Ni-mediated hydrazine disproportionation to N₂ and NH₃ completes the catalytic cycle.     

Physico-chemical aspects of polyethylene processing in an open mixer. Part 28: Formal kinetics of aldehyde and carboxylic acid formation in the advanced stages

The rate of acid formation at high temperature is constantly increasing but temperature independent. Two main mechanisms can account for this behavior in the advanced stages of polyethylene processing. The first mechanism is based on free radical induced oxidation of aldehyde pairs that are formed on acid-catalyzed decomposition of allylic hydroperoxides. The last will be formed essentially on mechanical stress-induced oxygen addition to trans-vinylene groups. Peroxidation of one of the aldehydes might yield an acyl-peroxy radical that is likely to abstract the labile hydrogen atom from the second aldehyde. The acyl radical formed in the reaction will abstract a hydroxyl group from the peracid formed in the same reaction. This yields an acid and an acyl-oxy radical that will give a primary alkyl radical on decarboxylation. The second mechanism involves oxidation of ketones and alcohols that accumulate in the oxidizing melt. Acid-catalyzed decomposition of the α-keto-hydroperoxides yields simultaneously an acid and an aldehyde. Formal kinetics based on each mechanism shows that they do not involve significant activation energy, as it is required by the experimental data. The dependency on the oxygen concentration deduced from the formal kinetics for the oxidation of aldehyde pairs is in agreement with the experiments.     

Activation and Deactivation of Benzylic C−H Bonds Guided by Stereoelectronic Effects in Hydrogen Atom Transfer from Amides and Amines to Alkoxyl Radicals

Kinetic and product studies on the reactions of tert-alkoxyl radicals with secondary and tertiary alkanamides bearing benzylic α-C−H bonds, isoindoline, tetrahydroisoquinoline and the corresponding N-acetyl derivatives were carried out. Product studies on the reactions with the tert-butoxyl radical (tBuO⋅) point toward exclusive HAT from the benzylic α-C−H bonds. Comparison of the k_H values measured for reaction with the cumyloxyl radical (CumO⋅) with those obtained previously for the corresponding reactions of N-alkyl- and N,N-dialkylalkanamides, are indicative of a lack of benzylic activation and the operation of steric and stereoelectronic effects. Compared to N-methyl and N-ethyl groups, the presence of N-benzyl groups increases the barrier required to reach the optimal conformation for HAT, where the α-C−H bond to be cleaved is perpendicular to the plane of the amide, precluding concurrent overlap with the phenyl π-system. When the benzylic α-C−H bonds are in a conformation that allows for optimal overlap with both the phenyl π-system and the amide π-system or amine nitrogen lone pair, as in the isoindoline and tetrahydroisoquinoline derivatives, increases in k_H that exceed 2-orders of magnitude were observed, highlighting the strong contribution provided by stereoelectronic activation to these HAT processes.     

Mechanistic Insight into Peptidyl-Cysteine Oxidation by the Copper-Dependent Formylglycine-Generating Enzyme

The copper-dependent formylglycine-generating enzyme (FGE) catalyzes the oxygen-dependent oxidation of specific peptidyl-cysteine residues to formylglycine. Our QM/MM calculations provide a very likely mechanism for this transformation. The reaction starts with dioxygen binding to the tris-thiolate Cu^I center to form a triplet Cu^II-superoxide complex. The rate-determining hydrogen atom abstraction involves a triplet-singlet crossing to form a Cu^II−OOH species that couples with the substrate radical, leading to a Cu^I-alkylperoxo intermediate. This is accompanied by proton transfer from the hydroperoxide to the S atom of the substrate via a nearby water molecule. The subsequent O−O bond cleavage is coupled with the C−S bond breaking that generates the formylglycine and a Cu^II-oxyl complex. Moreover, our results suggest that the aldehyde oxygen of the final product originates from O₂, which will be useful for future experimental work.     

Carbene-Catalyzed Intermolecular Dehydrogenative Coupling of Aldehydes with C(sp3)−H Bonds

The development of catalyst-controlled methods for direct functionalization of two distinct C−H bonds represents an appealing approach for C−C formations in synthetic chemistry. Herein, we describe an organocatalytic approach for straightforward acylation of C(sp³)−H bonds employing readily available aldehyde as “acyl source” involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp³)−H bonds. The developed method affords a broad range of ketones under mild conditions. Mechanistically, simple ortho-cyanoiodobenzene is essential in the oxidative radical N-heterocyclic carbene catalysis to give a ketyl radical and C(sp³) radical through a rarely explored intermolecular hydrogen atom transfer pathway, rendering the acylative C−C formations in high efficiency under a metal- and light-free catalytic conditions. Moreover, the prepared products show promising anti-bacterial activities that shall encourage further investigations on novel agrochemical development.     

Pathways of the Extremely Reactive Iron(IV)-oxido complexes with Tetradentate Bispidine Ligands

The nonheme iron(IV)-oxido complex trans-N3-[(L¹)Fe^IV=O(Cl)]⁺, where L¹ is a derivative of the tetradentate bispidine 2,4-di(pyridine-2-yl)-3,7-diazabicyclo[3.3.1]nonane-1-one, is known to have an S=1 electronic ground state and to be an extremely reactive oxidant for oxygen atom transfer (OAT) and hydrogen atom abstraction (HAA) processes. Here we show that, in spite of this ferryl oxidant having the “wrong” spin ground state, it is the most reactive nonheme iron model system known so far and of a similar order of reactivity as nonheme iron enzymes (C−H abstraction of cyclohexane, −90 °C (propionitrile), t_1/2=3.5 sec). Discussed are spectroscopic and kinetic data, supported by a DFT-based theoretical analysis, which indicate that substrate oxidation is significantly faster than self-decay processes due to an intramolecular demethylation pathway and formation of an oxido-bridged diiron(III) intermediate. It is also shown that the iron(III)-chlorido-hydroxido/cyclohexyl radical intermediate, resulting from C−H abstraction, selectively produces chlorocyclohexane in a rebound process. However, the life-time of the intermediate is so long that other reaction channels (known as cage escape) become important, and much of the C−H abstraction therefore is unproductive. In bulk reactions at ambient temperature and at longer time scales, there is formation of significant amounts of oxidation product – selectively of chlorocyclohexane – and it is shown that this originates from oxidation of the oxido-bridged diiron(III) resting state.     

Photocatalytic Reductive Radical-Polar Crossover for a Base-Free Corey–Seebach Reaction

A metal-free generation of carbanion nucleophiles is of prime importance in organic synthesis. Herein we report a photocatalytic approach to the Corey–Seebach reaction. The presented method operates under mild redox-neutral and base-free conditions giving the desired product with high functional group tolerance. The reaction is enabled by the combination of photo- and hydrogen atom transfer (HAT) catalysis. This catalytic merger allows a C−H to carbanion activation by the abstraction of a hydrogen atom followed by radical reduction. The generated nucleophilic intermediate is then capable of adding to carbonyl electrophiles. The obtained dithiane can be easily converted to the valuable α-hydroxy carbonyl in a subsequent step. The proposed reaction mechanism is supported by emission quenching, radical–radical homocoupling and deuterium labeling studies as well as by calculated redox-potentials and bond strengths.     

Photoinduced Single-Electron Transfer as an Enabling Principle in the Radical Borylation of Alkenes with NHC–Borane

A photoinduced SET process enables the direct B−H bond activation of NHC–boranes. In contrast to common hydrogen atom transfer (HAT) strategies, this photoinduced reaction simply takes advantage of the beneficial redox potentials of NHC–boranes, thus obviating the need for extra radical initiators. The resulting NHC–boryl radical was used for the borylation of a wide range of α-trifluoromethylalkenes and alkenes with diverse electronic and structural features, providing facile access to highly functionalized borylated molecules. Labeling and photoquenching experiments provide insight into the mechanism of this photoinduced SET pathway.     

Silver-Promoted Fluorination Reactions of α-Bromoamides

Silver-promoted C−F bond formation in α-bromoamides by using AgF under mild conditions is reported. This simple method enables access to tertiary, secondary, and primary alkyl fluorides involving biomolecular scaffolds. This transformation is applicable to primary and secondary amides and shows broad functional-group tolerance. Kinetics experiments revealed that the reaction rate increased in the order of 3°>2°>1° α-carbon atom. In addition, it was found that the acidic amide proton plays an important role in accelerating the reaction. Mechanistic studies suggested generation of an aziridinone intermediate that undergoes subsequent nucleophilic addition to form the C−F bond with stereospecificity (i.e., retention of configuration). The synthesis of sterically hindered alcohols and ethers by using Ag^I is also demonstrated. Examples of reactions of α-bromoamides with O nucleophiles are presented.     

New Radical Route and Insight for the Highly Efficient Synthesis of Benzimidazoles Integrated with Hydrogen Evolution

Benzimidazoles are a versatile class of scaffolds with important biological activities, whereas their synthesis in a lower-cost and more efficient manner remains a challenge. Here, we demonstrate a conceptually new radical route for the high-performance photoredox coupling of alcohols and diamines to synthesize benzimidazoles along with stoichiometric hydrogen (H₂) over Pd-decorated ultrathin ZnO nanosheets (Pd/ZnO NSs). The mechanistic study reveals the unique advantage of ZnO NSs over other supports and particularly that the features of Pd nanoparticles in facilitating the cleavage of the α-C−H bond of alcohols and adsorbing subsequently-generated C-centered radicals hold the key to turning on the reaction. This work highlights a new insight into radical-induced efficient benzimidazole synthesis pairing with H₂ evolution by rationally designing semiconductor-based photoredox systems.     

Computational studies on the conformational preference of N-(Thiazol-2-yl) benzamide

N-(Thiazol-2-yl) benzamide 1 substructures are found in some of bioactive compounds. In some of protein/ligand co-crystals, the 1 moiety adopts a conformer in which the amide O and the thiazole S atoms are close. In fact, in the crystalline structure of 1 , the O—S distance is even shorter than Van der Waals radius. Although the natural bond orbital analysis finds a weak stabilizing interaction between O and S atoms, the attractive dipole–dipole interaction between the amide N─H and thiazole N atom seems to play a more significant role. Moreover, an intramolecular O—H hydrogen bonding in dimeric forms found to have an important role in the conformation preference of 1 . Computational details for the stability of conformers have been discussed using quantum theory of atoms in molecules, natural bond orbital (NBO) and noncovalent interaction index analysis.     

Visible-Light-Enabled C−H Functionalization by a Direct Hydrogen Atom Transfer Uranyl Photocatalyst

The development of the uranyl cation as a powerful photocatalyst is seriously delayed in comparison with the advances in its fundamental and structural chemistry. However, its characteristic high oxidative capability in the excited state ([UO₂]²⁺* (+2.6 V vs. SHE; SHE=standard hydrogen electrode) combined with blue-light absorption (hv=380 – 500 nm) and a long-lived fluorescence lifetime up to microseconds have reveals that the uranyl cation approaches an ideal photocatalyst for visible-light-driven organic transformations. Described herein is the successful use of uranyl nitrate as a photocatalyst to enable C(sp³)−H activation and C−C bond formation through hydrogen atom transfer (HAT) under blue-light irradiation. In particular, this operationally simple strategy provides an appropriate approach to the synthesis of diverse and valuable diarylmethane motifs. Mechanistic studies and DFT calculations have provided insights into the detailed mechanism of the photoinduced HAT pathway. This research suggests a general platform that could popularize promising uranyl photocatalytic performance.