Bond Activation Research Articles

Visible-Light-Induced ArC(sp3)-F Bond Activation in Aqueous Media: From DFT Study to Molecular Design.

Trifluoromethylarenes (ArCF3) are crucial bioisosteres in medicinal chemistry, but catalyst-free and controlled photo-activation of the ArC(sp3)-F bond remains a significant challenge. The photo-induced defluorination acyl fluoride exchange (photo-DAFEx) of m-trifluoromethylaniline, induced by ultraviolet light, emerges as a promising novel photo-click reaction for photoaffinity drug discovery. However, the photophysical properties of NMe2PhF2C(sp3)-F derivatives and factors affecting ArC(sp3)-F bond activation in photo-DAFEx are not yet fully understood, hindering the development of new photo-defluorination reagents with longer absorption wavelength for the photo-DAFEx. Herein, the photophysical properties, the related mechanism and their affecting factors of a series of ArCF3 compounds are systematically studied using (TD)DFT methods. The skeleton of aromatic core is found to be intimately related to the absorption wavelength needed for ArC(sp3)-F bond activation. A photo-induced intramolecular single-electron activation model was proposed to rationalize the photo-activation of the ArC(sp3)-F bond. The transfer of excited electron to C(sp3)-F antibonding orbital determined the activation. Based on the above knowledge, three novel ArCF3 reagents with extended excitation wavelength were designed and predicted, and the absorption spectra and photo-defluorination reactivity of two of them with visible absorption wavelength were validated experimentally, which provided a theoretical guidance for designing next-generation photo-DAFEx.

Merger of Single-Atom Catalysis and Photothermal Catalysis for Future Chemical Production.

Photothermal catalysis is an emerging field with significant potential for sustainable chemical production processes. The merger of single-atom catalysts (SACs) and photothermal catalysis has garnered widespread attention for its ability to achieve precise bond activation and superior catalytic performance. This review provides a comprehensive overview of the recent progress of SACs in photothermal catalysis, focusing on their underlying mechanisms and applications. The dynamic structural evolution of SACs during photothermal processes is highlighted, and the current advancements and future perspectives in the design, screening, and scaling up of SACs for photothermal processes are discussed. This review aims to provide insights into their continued development in this rapidly evolving field.

Sb‐to‐P Metathesis: A Direct Route to Structurally Constrained, Cationic PIII Compound

AbstractStructurally constrained, cationic PIII compound [LP][SbCl4] with an OCO pincer‐type ligand (L) having a central carbene donor was directly synthesized via an Sb‐to‐P metathesis reaction between PCl3 and LSb‐Cl. [LP][SbCl4] was isolated and its reactivity with small molecules (ROH and RNH2) was studied, showing that [SbCl4]− is not an innocent counter anion, but an active participant in these reactions. When the [SbCl4]− was replaced with the [CB11H12]− ([Cb]−) anion, the reactions were redirected to [LP]+ cation only. The reactions with alcohols and amines led to the equilibrium between the products of the formal E−H (E=O, N) bond oxidative addition to the P‐center and products of the P‐center/ligand‐assisted bond activation. Remarkably, [LP]+ activated the PhO−H and PhN(H)−H bonds in a reversible, thermoneutral fashion.

Synthesis of Functionalized Benzo[f]chromanes and Hydroxyalkyl Naphthols: Catalytic Coupling of Naphthols and Allylic Alcohols

AbstractCatalytic dearomatization of arenols is an uphill task that can serve as a powerful method to construct C−C bonds with unsaturated coupling partners. Herein, a simple and efficient strategy for coupling naphthols with allylic alcohols is reported. A single Ru(II) pincer catalyzed coupling of naphthols with primary allylic alcohols led to the formation of benzo(f)chromanes, whereas the use of secondary alcohols delivered the hydroxyalkyl naphthols. Broad substrate scope and good functional group tolerance are demonstrated. Notably, a high diastereoselectivity is attained on chromanes. Hydroxyalkyl naphthols are synthetically transformed into spiroethers, and dearomative bromination is achieved on chromanes. Mechanistic studies revealed the involvement of tandem reactions, a formal O−H bond activation of allylic alcohols by an active catalyst via amine‐amide metal‐ligand cooperation provided α‐β, unsaturated carbonyl intermediates, which further underwent 1,4 conjugate addition with dearomatized naphthols. One of the crucial intermediates, naphthyl radical, is elucidated by EPR studies and trapped using a radical scavenger. Liberated hydrogen and water molecules are the only byproducts in these transformations.

Molecular-level Modulation of N, S-Co-Doped Mesoporous Carbon Nanospheres for Selective Aqueous Catalytic Oxidation of Ethylbenzene.

Selective oxidation of aromatic alkanes into high value-added products through benzylic C-H bond activation is one of the main reactions in chemical industry. On account of the constantly increasing demand for mass production, efficient, eco-friendly and sustainable catalysts are urgently needed. Herein, we describe a facile and versatile emulsion-assisted interface self-assembly strategy towards molecular-level fabrication of co-doped mesoporous carbon nanospheres with controllable active N and S species. The method enables a high degree of control over nanoparticle sizes, mesoporous nanostructures, contents of heteroatoms and the chemical composition. The optimized catalyst exhibits high catalytic performance of 97 % ethylbenzene conversion and 98 % selectivity to acetophenone. Density functional theory simulations reveal that N, S-co-doping leads to the redistribution of charge and spin densities, introducing more active carbon atoms and realizing aerobic oxidation of ethylbenzene efficiently. This work presents a general strategy for molecular-level design of carbon-based catalysts, and also provides new insight into the influence of heteroatom-doping on catalytic properties.

Disrupted Spin Degeneracy Promoted C≡C Triple Bond Activation for Efficient Electrochemical Acetylene Semihydrogenation

Disrupted Spin Degeneracy Promoted C≡C Triple Bond Activation for Efficient Electrochemical Acetylene Semihydrogenation

Tailoring the Coordination Environment of Cu Single Atoms for Achieving Regioselective C–C Bond Activation of Amides

Tailoring the Coordination Environment of Cu Single Atoms for Achieving Regioselective C–C Bond Activation of Amides

In situ growth of bismuth oxybromide/bismuth molybdate 2D/2D Z-scheme heterojunctions with rich interfacial oxygen vacancies for photocatalytic benzylic C(sp3)-H bond activation

The selective oxidation of toluene into valuable chemicals via photocatalytic C(sp3)-H bond activation represents a significant, yet challenging process. Here, the in situ construction of bismuth oxybromide/bismuth molybdate (BiOBr/Bi2MoO6) 2D/2D Z-scheme heterojunctions featuring interface-induced oxygen vacancies (OVs) is introduced. The optimized BiOBr/Bi2MoO6 sample has a remarkable yield rate of benzaldehyde at 2134.28 μmol g−1 h−1 under blue LED irradiation, surpassing the performance of BiOBr and Bi2MoO6 by 8.1 and 2.9 times, respectively. Insights from density functional theory (DFT) calculations, electron paramagnetic resonance (EPR), and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) studies highlight the critical role of the Z-scheme electronic configuration and OVs in attaining the superior photocatalytic toluene conversion efficiency. This study advances the photocatalytic conversion of benzaldehyde within an OV-enhanced direct Z-scheme system, facilitating the activation of inert C(sp3)-H bonds, and contributes to the development of high-performance catalysts for sustainable chemical processes.

Cyclometalated IrIII Complex Possessing Chiral MIC ligand: Regiospecific sp3 C-H Activation and Asymmetric Transfer Hydrogenation of Ketone.

Cyclometalation offers a wide number of organometallic metallacycles showing diverse applications. However, such NHC complexes synthesized via an sp3 C-H bond activation are rare. An iridium(III) complex with a chiral mesoionic N-heterocyclic carbene (MIC) ligand, where the IrIII forms an additional Ir-C bond via a regiospecific sp3 C-H bond activation at the N-methylbenzyl wingtip, was synthesized and characterized. To our best knowledge, this represents the first example of cyclometalated iridium(III) complex possessing a chiral MIC donor ligand. The formation of the complex was followed by 2D correlation NMR spectroscopy and the molecular formula mass was evidenced by ESI-HRMS mass spectrometry. The molecular structure of the IrIII-MIC complex was unambiguously established by the single crystal XRD data. This cyclometalated IrIII complex was employed in the asymmetric transfer hydrogenation of 4-bromoacetophenone, and the complex was successful to transfer chirality to the final alcohol molecules (up to 92% ee).

Competition of C–F, C–S, and S–F Bond Activation in SF5CF3 Using N‐Heterocyclic Olefins Derivatives: A Computational Study

ABSTRACTSF5CF3, commonly recognized as a potent greenhouse gas, has recently emerged as a valuable source of fluoride functional groups. Despite its traditional role, recent studies have highlighted its potential applications beyond its environmental implications. However, investigations into its reactivity remain limited, particularly regarding the activation of its constituent bonds. In this study, we conducted a comprehensive computational analysis to elucidate the competition among C–F, C–S, and S–F bond activations within SF5CF3 utilizing N‐heterocyclic olefin derivatives. Our investigations shed light on the underlying mechanisms of bond activation, revealing a preference for the activation of the S–F bond in SF5CF3 by both NHOs and mNHOs. Specifically, we observed a Gibbs free energy barrier (ΔG≠) ranging from 24.90 to 25.77 kcal/mol in the case of mNHOs, indicating a favorable energetics for this process.

Alkanes C1-C6 C-H Bond Activation via a Barrierless Potential Energy Path: Trifluoromethyl Carbenes Enhance Primary C-H Bond Functionalization.

In this mixed computational and experimental study, we report a catalytic system for alkane C1-C6 functionalization in which the responsible step for C-H bond activation shows no barrier in the potential energy path. DFT modeling of three silver-based catalysts and four diazo compounds led to the conclusion that the TpFAg═C(H)CF3 (TpF = fluorinated trispyrazolylborate ligand) carbene intermediates interact with methane without a barrier in the potential energy surface, a prediction validated by experimentation using N2═C(H)CF3 as the carbene source. The array of alkanes from propane to n-hexane led to the preferential functionalization of the primary sites with unprecedented values of selectivity for an acceptor diazo compound. The lack of those barriers implies that selectivity can no longer be controlled by differences in the energy barriers. Molecular dynamics calculations (with propane as the model alkane) are consistent with the preferential functionalization of the primary sites due to a higher concentration of such C-H bonds in the vicinity of the carbenic carbon atom.

Carbon-Bromide Bond Activation by Bidentate Halogen, Chalcogen, Pnicogen, and Tetrel Bonds.

Halogen, chalcogen, pnictogen, and tetrel bonds in organocatalysis have gained noticeable attention. In this work, carbon-bromide bond activation in the Ritter reaction by bidentate imidazole-type halogen, chalcogen, pnicogen, and tetrel bond donors was studied by density functional theory. All of the above four kinds of catalysts exhibited excellent catalytic performance. σ-hole interactions were formed between the Br atom of the reactant and the halogen, chalcogen, pnicogen, and tetrel bond donors, which elongated the C-Br bond and caused the rearrangement of the electron density of the precomplexes, resulting in the breaking of the C-Br bond and Br abstraction. Notably, the catalytic activity of the chalcogen bond is the best, followed by that of the halogen bond. Although the catalytic activity of pnicogen and tetrel bond catalysts is not as good as that of the halogen bond and chalcogen bond, they can still be used as effective substitutes for the halogen bond and chalcogen bond, providing more choices for noncovalent catalysis. Furthermore, within the same group, the fifth-period atomic catalyst is more effective than the fourth-period one for halogen, chalcogen, pnicogen, and tetrel bond donor catalysts.

Pd-Catalyzed Decarbonylative Suzuki-Miyaura Cross-Coupling of Pyramidalized N-Mesyl Amides by a Tandem N-C(O)/C-C Bond Activation.

The Suzuki-Miyaura biaryl cross-coupling is the pivotal technology for carbon-carbon coupling in pharmaceutical, polymer, and agrochemical fields. A long-standing challenge has been the development of efficient precursors for the decarbonylative cross-coupling of amide bonds. Herein, we report a highly chemoselective palladium-catalyzed Suzuki-Miyaura cross-coupling of N-mesyl amides for the synthesis of biaryls by a tandem N-C(O)/C-C bond activation with high selectivity for decarbonylative cleavage. The results demonstrate the first example of a decarbonylative coupling (-CO) of amide bonds activated by an atom-economic, low-cost, and benign N-pyramidalized mesyl group (>30 examples). The reaction shows high generality and functional group tolerance and can be applied in late-stage functionalization of pharmaceuticals. Notably, N-mesyl amides are significantly more reactive than other classes of amides in the decarbonylative Suzuki cross-coupling manifold. Density functional theory (DFT) studies demonstrate considerably lower barrier for rate-limiting transmetalation using N-mesyl amides. The study establishes N-mesyl amides as versatile precursors for Suzuki-Miyaura cross-coupling to afford valuable biaryls and opens the door to deploy N-mesyl amides in challenging cross-couplings of amides by decarbonylation.

Recent Advances in C-O Bond Cleavage of Aryl, Vinyl, and Benzylic Ethers.

Transition metal-catalyzed cross-coupling with aryl halides has revolutionized the way of diversifying aromatic compounds. Aryl ethers are attractive alternatives to aromatic halides as coupling partners considering the accessibility and potential environmental benefits. The last two decades have witnessed a striking success in the field of C-O bond activation of aryl ethers, including the construction of C-C bond and C-X bond, as well as reductive deoxygenation. Here, we present a comprehensive review of C-O bond activation in the context of aryl, vinyl, and benzylic ethers. This review elaborates on the current state-of-the-art methods, categorized by different catalytic systems, including transition metal catalysis, photoredox catalysis, and other innovative approaches. The newly developed methods allow C-O bond activation under mild conditions with exceptional functional group tolerance, potentially enabling the late-stage functionalization of pharmaceuticals. The limitations and future perspectives of the methods are also presented.

Sb-to-P Metathesis: A Direct Route to Structurally Constrained, Cationic PIII Compound.

Structurally constrained, cationic PIII compound [LP][SbCl4] with an OCO pincer-type ligand (L) having a central carbene donor was directly synthesized via an Sb-to-P metathesis reaction between PCl3 and LSb-Cl. [LP][SbCl4] was isolated and its reactivity with small molecules (ROH and RNH2) was studied, showing that [SbCl4]- is not an innocent counter anion, but an active participant in these reactions. When the [SbCl4]- was replaced with the [CB11H12]- ([Cb]-) anion, the reactions were redirected to [LP]+ cation only. The reactions with alcohols and amines led to the equilibrium between the products of the formal E-H (E=O, N) bond oxidative addition to the P-center and products of the P-center/ligand-assisted bond activation. Remarkably, [LP]+ activated the PhO-H and PhN(H)-H bonds in a reversible, thermoneutral fashion.

In-situ homologous bromine vacancies for enhanced C-Br bond activation and rapid debromination of decabromodiphenyl ether

Polybrominated diphenyl ethers (PBDEs) have attracted increasing attention due to their biotoxicity and persistence. Herein, rapid degradation of decabromodiphenyl ether (BDE209) was achieved on bromine vacancies enriched BiOBr (BOB-VBr) nanosheets, with a degradation rate for BDE209 under visible light irradiation (λ > 400 nm) exceeding 95 % within 6 min. The initial two minutes serve as an induction period, during which the Br vacancies were in-situ introduced into the BiOBr (BOB) nanosheets. By precisely controlling the duration of photoinduction, varying concentrations of Br vacancies were successfully generated on the surface of the BOB nanosheets. Consequently, an enhanced degradation rate of BDE209 was observed in direct correlation with the increased concentration of Br vacancies. BOB-VBr showed a remarkable selectivity of 74 % for meta-product (BDE207). This selectivity towards BDE207 surpasses that of other anionic vacancies, as oxygen, sulfur, and iodine vacancies. The in-situ generated Br vacancies help to accommodate the Br atom of BDE209 in atomic size and electronic structure, thus facilitating the activation of the C-Br bond and achieving rapid BDE209 debromination. This work provides a new insight for the treatment of organic halogenated pollutants by photocatalysts with homologous halogen vacancies.

Plasmon-driven molecular scission

Abstract Plasmon-driven photocatalysis offers a unique means of leveraging nanoscale light–matter interactions to convert photon energy into chemical energy in a chemoselective and regioselective manner under mild reaction conditions. Plasmon-driven bond cleavage in molecular adsorbates represents a critical step in virtually all plasmon-mediated photocatalytic reactions and has been identified as the rate-determining step in many cases. This review article summarizes critical insights concerning plasmon-triggered bond-cleaving mechanisms gained through combined experimental and computational efforts over the past decade or so, elaborating on how the plasmon-derived physiochemical effects, metal–adsorbate interactions, and local chemical environments profoundly influence chemoselective bond-cleaving processes in a diverse set of molecular adsorbates ranging from small diatomic molecules to aliphatic and aromatic organic compounds. As demonstrated by several noteworthy examples, insights gained from fundamental mechanistic studies lay a critical knowledge foundation guiding rational design of nanoparticle–adsorbate systems with desired plasmonic molecule-scissoring functions for targeted applications, such as controlled release of molecular cargos, surface coating of solid-state materials, and selective bond activation for polymerization reactions.

Photocatalytic C-F bond activation in small molecules and polyfluoroalkyl substances.

Organic halides are highly useful compounds in chemical synthesis, where the halide serves as a versatile functional group for elimination, substitution, and cross-coupling reactions with transition metals or photocatalysis1-3. However, the activation of carbon-fluorine bonds, the most commercially abundant organohalide and found in PFAS, or "forever chemicals", are much rarer. Current approaches based on photoredox chemistry for activation of small molecule carbon-fluorine (C-F) bonds are limited by the substrates and transition-metal catalysts needed4. A general method for the direct activation of organofluorines would have significant value in organic and environmental chemistry. Here, we report an organic photoredox catalyst system that can efficiently reduce C-F bonds to generate carbon-centered radicals, which can then be intercepted for hydrodefluorination (swapping F for H) and cross-coupling reactions. This system enables the general use of organofluorines as synthons under mild reaction conditions. We extend this method to the defluorination of polyfluoroalkyl substances (PFAS) and fluorinated polymers, a critical challenge in the breakdown of persistent and environmentally damaging forever chemicals.

Hexafluorophosphate-Triggered Hydrogen Isotope Exchange (HIE) in Fluorinated Environments: A Platform for the Deuteration of Aromatic Compounds via Strong Bond Activation.

There is a perpetual need for efficient and mild methods to integrate deuterium atoms into carbon frameworks through late-stage modifications. We have developed a simple and highly effective synthetic route for hydrogen isotope exchange (HIE) in aromatic compounds under ambient conditions. This method utilizes catalytic amounts of hexafluorophosphate (PF6-) in deuterated 1,1,1,3,3,3-hexafluoroisopropanol (HFIP-d1) and D2O. Phenols, anilines, anisoles, and heterocyclic compounds were converted with high yields and excellent deuterium incorporations, which allows for the synthesis of a wide range of deuterated aromatic compounds. Spectroscopic and theoretical studies show that an interactive H-bonding network triggered by HFIP-d1 activates the typically inert P-F bond in PF6- for D2O addition. The thus in-situ formed DPO2F2 triggers then HIE, offering a new way to deuterated building blocks, drugs, and natural-product derivatives with high deuterium incorporation via the activation of strong bonds.

N-H Bond Activation of Ammonia by a Redox-Active Carboranyl Diphosphine.

In this work, we report the room-temperature N-H bond activation of ammonia by the carboranyl diphosphine 1-PtBu2-2-PiPr2-closo-C2B10H10 (1) resulting in the formation of zwitterionic 7-P(NH2)tBu2-10-P(H)iPr2-nido-C2B10H10 (2). Unlike the other phosphorus-based ambiphiles that require geometric constraints to enhance electrophilicity, the new mode of bond activation in this main-group system is based on the cooperation between electron-rich trigonal phosphine centers and the electron-accepting carborane cluster. As an exception among many other metal-based and metal-free systems, the N-H bond activation of gaseous ammonia or aqueous ammonium hydroxide by carboranyl diphosphine 1 proceeds with tolerance of air and water. Mechanistic details of ammonia activation were explored computationally by DFT methods, demonstrating an electrophilic activation of ammonia by the phosphine center. This process is driven by the reduction of the boron cluster followed by an ammonia-assisted deprotonation and proton transfer. A subsequent reaction of 2 and TEMPO results in the cleavage of all N-H and P-H bonds with the formation of a cyclic phosphazenium cation supported by an anionic cluster N(7-PtBu2-8-PiPr2)-nido-C2B9H10 (3). Transformations reported herein represent the first example of ammonia oxidation via triple hydrogen atom abstraction facilitated by a metal-free system.