Captodative Research Articles

Stabilized Carbon-Centered Radical-Mediated Carbosulfenylation of Styrenes: Modular Synthesis of Sulfur-Containing Glycine and Peptide Derivatives.

Sulfur-containing amino acids and peptides play critical roles in organisms. Thiol-ene reactions between the thiol residues of L-cysteine and the alkenyl fragments in the designed coupling partners serve as primary tools for constructing C─S bonds in the synthesis of unnatural sulfur-containing amino acid derivatives. These reactions are favored due to the preference for hydrogen transfer from thiol to β-sulfanyl carbon radical intermediates. In this paper, the study proposes utilizing carbon-centered radicals stabilized by the capto-dative effect, generated under photocatalytic conditions from N-aryl glycine derivatives. The aim is to compete with the thiol hydrogen, enabling radical C─C bond formation with β-sulfanyl carbon radicals. This protocol is robust in the presence of air and water, offers significant potential as a modular and efficient platform for synthesizing sulfur-containing amino acids and modifying peptides, particularly with abundant disulfides and styrenes.

Photo-oxidative aromatization and photo-rearrangement of 2, 4-diaryl-5-oxohexahydroquinolines

Various 2,4-bisaryl substituted 5-oxohexahydroquinolines were synthesized and the electronic effects of 2- and 4-substitutions on the photochemical behaviors of these compounds were investigated. UV light irradiation of these compounds resulted in the occurrence of two types of photoreactions; oxidative normal photo-oxidation and photo-rearranged reactions. In both reactions, the aromatization of the heterocyclic 1,4-dihydropyridine ring to the pyridine ring was observed. The photochemical results indicated the involvement of the radical intermediate, responsible for the aryl ring migration and the occurrence of the photo-rearrangement reaction. The partial synergistic effect of the capto-dative radical stabilization of the involved radical intermediate was supported by the results of the experimental works and the DFT-computational studies. X-ray crystal structure analysis of two of 5-oxohexahydroquinoline compounds indicated that i). The C4-aryl ring occupies the pseudo-axial position of the twisted-boat conformation of the heterocyclic dihydropyridine ring and, ii). Owing to the steric ortho-repulsion, the C2-aryl ring has a non-planar orientation concerning the attached CC double bond of the heterocyclic ring. These observations were in good agreement with the data of the DFT-computational studies and the X-ray crystal structure analysis.

Generation and Aerobic Oxidation of Azavinyl Captodative Radicals.

We describe a cascade reaction that selectively incorporates oxygen into the carbon-carbon backbone of alkynes using air as the source. The process starts by lithiating readily available, electron-deficient 1,2,3-triazoles, resulting in an amphoteric lithium ketenimine intermediate. This intermediate can react with both electrophiles and nucleophiles. Under the conditions outlined in this study, we generate azavinyl radicals, which are a rare subset of captodative radicals. When exposed to atmospheric oxygen, these radicals efficiently transform into α-oxygenated amidines─a class of compounds that has not been extensively studied. This process uniquely utilizes molecular oxygen without requiring metal or photocatalysts, and it occurs under mild conditions. Our mechanistic studies provide insights into the intricate sequence involved in the formation and selective capture of azavinyl captodative radicals.

Cover Feature: Origin of the Captodative Effect: The Lone‐Pair Shielded Radical (ChemistryEurope 1/2023)

Cover Feature: Origin of the Captodative Effect: The Lone‐Pair Shielded Radical (ChemistryEurope 1/2023)

Origin of the Captodative Effect: The Lone‐Pair Shielded Radical

AbstractWe have quantum chemically analyzed the origin of the captodative effect in the dimerization of para‐substituted phenyl dicyanomethyl radicals RPh(CN)2C⋅ in the gas phase and in solution. Captodative radicals are characterized by the presence of both, electron‐donating and electron‐withdrawing groups, and a weakening of the associated C−C bond in the dimer of these radicals. Our quantitative bonding analyses reveal that the captodative weakening of the C−C bond is the consequence of a special feature in the RPh(CN)2C⋅ electronic structure which we designate “lone‐pair shielded radical”. Solvation effects weaken the C−C bond as the radicals have a more prominent internal charge separation than the dimer and are, therefore, stabilized more than the intact dimer. Interestingly, we find that differences in solvent effects as a function of the para‐substituent in the most prominent case arise from variations in the charge distribution in the dimer, not from that in the separate radicals which experience very similar solvation in those instances.

Lewis Acid-Mediated Radical Stabilization and Dynamic Covalent Bonding: Tunable, Reversible and Photocontrollable.

This work describes a strategy not only to isolate a dynamically stable radical with physical property tunability, but to efficiently regulate the radical dissociation with reversibility and photo controllability. The addition of Lewis acid B(C6 F5 )3 (BCF) into the solution of a radical σ-dimer (1-1) led to a stable radical (1⋅-2B), which has been characterized by EPR spectroscopy, UV/Vis spectroscopy and single crystal X-ray diffraction, in conjunction with theoretical calculation. The radical species is stabilized mainly by captodative effect, single electron transfer and steric effect. The absorption maximum of the radical can be tuned by using different Lewis acids. Dimer 1-1 can be achieved back by addition of a stronger base into the solution of 1⋅-2B, exhibiting a reversible process. By introducing a photo BCF generator, the dissociation of the dimer and the formation of the radical adduct become photocontrollable.

Lewis Acid‐Mediated Radical Stabilization and Dynamic Covalent Bonding: Tunable, Reversible and Photocontrollable

AbstractThis work describes a strategy not only to isolate a dynamically stable radical with physical property tunability, but to efficiently regulate the radical dissociation with reversibility and photo controllability. The addition of Lewis acid B(C6F5)3 (BCF) into the solution of a radical σ‐dimer (1‐1) led to a stable radical (1⋅‐2B), which has been characterized by EPR spectroscopy, UV/Vis spectroscopy and single crystal X‐ray diffraction, in conjunction with theoretical calculation. The radical species is stabilized mainly by captodative effect, single electron transfer and steric effect. The absorption maximum of the radical can be tuned by using different Lewis acids. Dimer 1‐1 can be achieved back by addition of a stronger base into the solution of 1⋅‐2B, exhibiting a reversible process. By introducing a photo BCF generator, the dissociation of the dimer and the formation of the radical adduct become photocontrollable.

Captodative Effect Facilitates the Excitation in Diboron Molecule (CAAC)2 B2 (SH)2.

Given the extraordinary versatility in chemical reactions and applications, boron compounds have gained increasing attentions in the past two decades. One of the remarkable advances is the unprecedented preparation of unsaturated boron species. Notably, Braunschweig et al. found that the cyclic (alkyl)(amino) carbenes (CAACs) stabilized diboron molecules (CAAC)2 B2 (SR)2 host unpaired electrons and exist in the 90°-twisted diradical form, while other analogues, such as N-heterocyclic carbenes (NHCs), stabilized diboron molecules prefer a conventional B=B double bond. Since previous studies recognized the differences in the steric effect between CAAC and NHC carbenes, here we focused on the role of thiol substituents in (CAAC)2 B2 (SR)2 by gradually localizing involved electrons. The co-planarity of the thiol groups and the consequent captodative effect were found to be the culprit for the 90°-twisted diradical form of (CAAC)2 B2 (SR)2 . Computational analyses identified two forces contributing to the π electron movements. One is the "push" effect of lone pairs on the sulfur atoms which boosts the π electron delocalization between the BB center and CAACs. The other is the π electron delocalization within each (CAAC)B(SR) fragment where the pull effect originates from the π electron withdrawal by CAACs. There are two such independent and orthogonal push-pull channels which function mainly in individual (CAAC)B(SR) fragments. This enhanced π push-pull effect in the triplet state facilitates the electronic excitation in (CAAC)2 B2 (SR)2 by reducing the singlet-triplet gap.

An air-stable radical with a redox-chameleonic amide.

An air-stable (amino)(amido)radical was synthesized by reacting a cyclic (alkyl)(amino)carbene with carbazoyl chloride, followed by one-electron reduction. We show that an adjacent radical center weakens the amide bond. It enables the amino group to act as a strong acceptor under steric contraint, thus enhancing the stabilizing capto-dative effect.

Medium Diradical Character, Small Hole and Electron Reorganization Energies and Ambipolar Transistors in Difluorenoheteroles

Four difluorenoheteroles having a central quinoidal core with the heteroring varying as furan, thiophene, its dioxide derivative and pyrrole have shown to be medium character diradicals. Solid-state structures, optical, photophysical, magnetic, and electrochemical properties have been discussed in terms of diradical character, variation of aromatic character and captodative effects (electron affinity). Organic field-effect transistors (OFETs) have been prepared, showing balanced hole and electron mobilities of the order of 10−3 cm2 V−1 s−1 or ambipolar charge transport which is first inferred from their redox amphoterism. Quantum chemical calculations show that the electrical behavior is originated from the medium diradical character which produces similar reorganization energies for hole and electron transports. The vision of a diradical as simultaneously bearing pseudo-hole and pseudo-electron defects might justify the reduced values of reorganization energies for both regimes. Structure-function relationships between diradical and ambipolar electrical behavior are revealed.

Medium Diradical Character, Small Hole and Electron Reorganization Energies and Ambipolar Transistors in Difluorenoheteroles.

Four difluorenoheteroles having a central quinoidal core with the heteroring varying as furan, thiophene, its dioxide derivative and pyrrole have shown to be medium character diradicals. Solid‐state structures, optical, photophysical, magnetic, and electrochemical properties have been discussed in terms of diradical character, variation of aromatic character and captodative effects (electron affinity). Organic field‐effect transistors (OFETs) have been prepared, showing balanced hole and electron mobilities of the order of 10−3 cm2 V−1 s−1 or ambipolar charge transport which is first inferred from their redox amphoterism. Quantum chemical calculations show that the electrical behavior is originated from the medium diradical character which produces similar reorganization energies for hole and electron transports. The vision of a diradical as simultaneously bearing pseudo‐hole and pseudo‐electron defects might justify the reduced values of reorganization energies for both regimes. Structure‐function relationships between diradical and ambipolar electrical behavior are revealed.

Computational design of singlet fission biradicaloid chromophores

We present three different computational designs of potential singlet fission chromophores. In the first two cases, we propose structural modifications of two biradicaloid compounds already known with regard to singlet fission, namely 1,3-diphenyl-isobenzofuran (DPBF) and 2,3-diamino-1,4-benzoquinone (DABQ). In the former case, the introduction of methylene bridges between the phenyl rings and the isobenzofuran core of DPBF leads to an improvement of the singlet fission energetics and confers a higher degree of rigidity to the resulting molecule. In the second case, structural modifications of DABQ are proposed in order to overcome its fast nonradiative excited state decay and to improve its singlet fission energetics. The resulting diamino-fluoroquinone compounds fulfill the desired energy criteria and represent new potential chromophores for singlet fission. Finally, in the third proposed design we exploit the captodative effect to tune the energy levels of small biradicaloid molecules, leading to propose several compounds presented for the first time as suitable chromophores for singlet fission.

Polymer chemistry of α-substituted acrylates designed for functional-group synergy

This article overviews the polymer chemistry of acrylates designed for functional-group synergy among the vinyl group and ester- and α-substituents. α-Substituents have been incorporated to tune the reactivity of the vinyl group; for example, ethyl α-cyanoacrylate, known as instant adhesions, has high reactivity to initiate anionic polymerization using moisture. Moreover, α-acyloxyacrylates undergo radical polymerization, increasing the degree of polymerization in proportion to monomer conversions due to the stabilized radical species by the captodative effect. α-Arylacrylates produced alternating copolymers with methyl methacrylate (MMA) using anionic polymerization, which exhibited specific fluorescence. α-(Aminomethyl)acrylates stabilized by intramolecular hydrogen bonding yielded a pH-/thermo-responsive polymer. Anionic polymerization of α-(alkoxymethyl)acrylates resulted in high isotacticity due to the chelating effect at the propagating chain end. α-(Halomethyl)acrylates underwent a nucleophilic conjugate substation reaction, applied to end-functionalization, polycondensation, and polymer degradation. For a long time, ring-opening polymerization of cyclic acrylates has been considered difficult; however, it was recently achieved using sophisticated monomer design.

Aggregation-Induced Radical of Donor-Acceptor Organic Semiconductors.

Narrow bandgap donor-acceptor organic semiconductors are generally considered to show a closed-shell singlet ground state, and their radicals are reported as impurities, defects, polarons, and charge transfer monoradicals. Herein, we systematically investigated the open-shell singlet diradical electronic ground state of two diketopyrrolopyrrole-based compounds via the combination of electron spin resonance (ESR), nuclear magnetic resonance, superconducting quantum interference device magnetometry, and theoretical calculations. It is widely known that the quinoidal character will be significantly enhanced in the aggregation state accompanied by improved planarity and enhanced delocalization. We proposed an aggregation-induced radical and captodative effect as the driving force for the formation and stabilization of the open-shell quinoid diradical based on the ESR test in different proportions of mixed solvents. Our results provided a novel view for understanding the intrinsic chemical structure of donor-acceptor organic semiconductors, the open-shell singlet and thermally excited triplet electronic states, and the unexpected physical processes between the ground state and the excited state.

Electron doping of single-walled carbon nanotubes using pyridine-boryl radicals.

Pyridine-boryl (py-boryl) radicals serve as efficient electron-doping reagents for single-walled carbon nanotubes (SWCNTs). The doping mechanism comprises electron transfer from the py-boryl radical to the SWCNT. The formation of a stable py-boryl cation is essential for efficient doping; the captodative effect of the py-boryl cation is important to this process.

Theoretical Molecular Design of Phenanthrenes for Singlet Fission by Diazadibora-Substitution

Based on the valence configuration interaction (VCI) model and quantum chemical calculations, we theoretically investigate the potential of diazadibora-substituted phenanthrenes [(BN)2-phenanthrenes] as novel singlet fission (SF) chromophores. (BN)2-substitution to phenanthrene is performed to exhibit a captodative effect, which is found to enhance both diradical character and exchange integral. These enhanced parameters induced by (BN)2-substitution are shown to bring energetically favorable SF with high triplet excitation energies. In order to reveal the relationship between diradical character and positions replaced by (BN)2, analyses based on the VCI model, odd-electron density, and resonance structures are conducted. Accordingly, a concrete design principle, which is inherent in and is understandable from the topology of (BN)2-phenanthrene, is presented. Furthermore, design strategies to fine-tuning of the diradical character are newly demonstrated based on the additional introduction of π-donor and π-acceptor. The present results provide feasible candidate molecules and novel design strategies toward the discovery of bright SF chromophores for the application to efficient organic solar cells.

Molecular Design Principle for Efficient Singlet Fission Based on Diradical Characters and Exchange Integrals: Multiple Heteroatom Substitution Effect on Anthracenes

We theoretically investigate significant impacts of diradical characters and exchange integrals on the first singlet (S1) and triplet (T1) excitation energies related to singlet fission (SF), from which a series of C2h-symmetrically diazadibora-substituted anthracenes [(BN)2-anthracenes] are newly proposed as potential efficient SF chromophores. From the analytical expressions of electronic structures for a model system with two electrons in two orbitals, a tuning of exchange integrals represented by localized natural orbitals is shown to be effective to vary E(S1) and E(T1), in addition to the control of diradical characters, both of which are expected to result in SF isothermal or exothermic [E(S1) – 2E(T1) ≈ 0 or > 0]. The applicability of this strategy to realistic molecules is verified for multiple heteroatom substitution to anthracene, namely, (BN)2-anthracenes, by the complete active space configuration interaction method and the time-dependent density functional theory method. Our calculations show that (BN)2-anthracenes exhibit a wide range of diradical characters and enhanced exchange integrals, enabling flexible tunings of E(S1) and E(T1). Accordingly, several (BN)2-anthracenes are found to be promising candidates for efficient SF. Such a behavior of diradical character can be understood from resonance structures associated with the captodative effect. Moreover, a concrete strategy of tuning exchange integrals is demonstrated in terms of frontier molecular orbital distributions. The present results open up novel molecular design guidelines for efficient SF based on the tuning of exchange integrals in addition to diradical characters.

Tunable Electrochemical C-N versus N-N Bond Formation of Nitrogen-Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications.

Herein, an environmentally friendly electrochemical approach is reported that takes advantage of the captodative effect and delocalization effect to generate nitrogen-centered radicals (NCRs). By changing the reaction parameters of the electrode material and feedstock solubility, dearomatization enabled a selective dehydrogenative C-N versus N-N bond formation reaction. Hence, pyrido[1,2-a]benzimidazole and tetraarylhydrazine frameworks were prepared through a sustainable transition-metal- and exogenous oxidant-free strategy with broad generality. Bioactivity assays demonstrated that pyrido[1,2-a]benzimidazoles displayed antimicrobial activity and cytotoxicity against human cancer cells. Compound 21 exhibited good photochemical properties with a large Stokes shift (approximately 130 nm) and was successfully applied to subcellular imaging. A preliminary mechanism investigation and density functional theory (DFT) calculations revealed the possible reaction pathway.

Tunable Electrochemical C−N versus N−N Bond Formation of Nitrogen‐Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications

AbstractHerein, an environmentally friendly electrochemical approach is reported that takes advantage of the captodative effect and delocalization effect to generate nitrogen‐centered radicals (NCRs). By changing the reaction parameters of the electrode material and feedstock solubility, dearomatization enabled a selective dehydrogenative C−N versus N−N bond formation reaction. Hence, pyrido[1,2‐a]benzimidazole and tetraarylhydrazine frameworks were prepared through a sustainable transition‐metal‐ and exogenous oxidant‐free strategy with broad generality. Bioactivity assays demonstrated that pyrido[1,2‐a]benzimidazoles displayed antimicrobial activity and cytotoxicity against human cancer cells. Compound 21 exhibited good photochemical properties with a large Stokes shift (approximately 130 nm) and was successfully applied to subcellular imaging. A preliminary mechanism investigation and density functional theory (DFT) calculations revealed the possible reaction pathway.

Solvent Effects on the Stability and Delocalization of Aryl Dicyanomethyl Radicals: The Captodative Effect Revisited.

The captodative effect postulates that radicals substituted with both electron donating and accepting groups enjoy a special enhanced stabilization, a model given theoretical support by simple MO and resonance arguments. A key prediction from theory is that captodative stabilization of radicals is larger in polar solvents than in nonpolar solvents or the gas phase, which can be viewed in the resonance model as solvent stabilization of charge-separated resonance forms. Yet, several experimental studies have failed to observe a solvent effect on radical stability, casting doubt on key aspects of the captodative effect. Here, we examine in detail the effect of solvent on the stability of structurally related captodative aryl dicyanomethyl radicals. An attractive feature of these radicals is that they exist as stable steady state populations of radicals in equilibrium with their dimers, allowing us to directly characterize from experiment their thermodynamic stabilities and spin delocalization in solvents of varying polarity. In contrast to the prior studies, we find that captodative radicals are indeed stabilized by polar solvents, as measured by a shift in the radical-dimer association constants by up to 100-fold toward the radical upon going from nonpolar toluene to more polar DMF. Moreover, in polar solvents, the spin is shifted onto the donor substituent and away from the benzylic carbon. Within the resonance model, these results can be explained by the increased contributions of the zwitterionic resonance structures to the overall hybrid. These results provide experimental support to a key prediction from theory that had previously been dismissed.