Anionic Intermediates Research Articles

Experimental and Theoretical Studies on Stereomutation Through gem‐Difluorocyclopropanylide Intermediates

AbstractA desilylation process of optically active silyl‐substituted gem‐difluorocyclopropanes with tetrabutylammonium fluoride (TBAF) showed a substantial reduction of enantiopurity of the resultant gem‐difluorocyclopropanes even at ambient temperatures. The electron‐withdrawing aryl substituent at the 3‐position in the 1‐silyl‐2,2‐difluorocyclopropane system accelerated the racemization, indicating a correlation with the stability of the anionic intermediates. The plausible racemization pathway through homolytic cleavage of the distal bond in gem‐difluorocyclopropane is inconsistent with the experimental results because the high energy of >34 kcal/mol is required for generating the open‐shell 2,2‐difluoropropane‐1,3‐diyl skeleton. The DFT studies using the anionic 2,2‐difluoromethyl‐3‐phenylcyclopropanylide intermediate supported the alternative isomerization pathway through the intramolecular migration of hydrogen and the resultant thermodynamically stable 2,2‐difluoromethyl‐1‐phenylcyclopropanylide anion could facilitate the racemization process at the stereocenter. Although the transition state indicated considerable activation energies, the high frequency of imaginary vibration should correlate with a barrier of a very narrow width enabling quantum tunneling under the H‐migration step. The observed isotope effect is compatible with the proposed mechanism through the intramolecular H‐migration.

Palladium and copper co-catalyzed chloro-arylation of gem-difluorostyrenes - use of a nitrite additive to suppress β-F elimination.

The installation of fluorine and fluorinated functional groups in organic molecules perturbs the physicochemical properties of those molecules and enables the development of new therapeutics, agrichemicals, biological probes and materials. However, current synthetic methodologies cannot access some fluorinated functional groups and fluorinated scaffolds. One such group, the gem-difluorobenzyl motif, might be convergently synthesized by reacting a nucleophilic aryl precursor and an electrophilic gem-difluoroalkene. Previous attempts have relied on forming unstable anionic or organometallic intermediates that rapidly decompose through a β-F elimination process to deliver monofluorovinyl products. In contrast, we report a fluorine-retentive palladium and copper co-catalyzed chloro-arylation of gem-difluorostyrenes that takes advantage of a nitrite (NO2 -) additive to avoid the favorable β-F elimination pathway that forms monofluorinated products, instead delivering difluorinated products.

CO2 Transient Promotion Function Enabled the Selective Electrochemical Transformation of Imines.

An unprecedented transient promotion function (TPF) of CO2 in the electrochemical hydrogenation/deuteration of imines (especially α-iminonitriles) is reported. The TPF influence of CO2 results from the introduction of CO2 that disperses the negative charges of the imine radical anion intermediate. The resulting redistribution of electrons leads to a lower reduction potential of the CO2-substituted imine radical anion and thus facilitates the succeeding one-electron reduction. CO2 is finally released via spontaneous decarboxylation to complete the transient promotion process.

Mass spectrometric monitoring of ligand-bridged hot electron transfer and anaerobic oxidization on auto renewable droplet-based plasmonic nanoreactors under visible light illumination

The light induced hot-electron on plasmonic nanostructures has been recognized as a breakthrough discovery for photovoltaic and photocatalytic applications. With mass spectrometry, we demonstrate the dynamics of hot electron transfers of anaerobic oxidization reactions on Au decorated TiO2 plasmonic nanoparticles, which were coated on the inner surface of a flask. Those nanoparticles were covered by continuously renewed liquid droplets of solvent and reactants that were transported through a Venturi jet mixer with auto-spray. In addition to intensive mass transfer in such droplet-based nanoreactors, as well as strong adsorption of reactants and rapid desorption of products on materials surfaces, the localized surface plasmon resonance (LSPR) excitation upon visible light illumination, by which accumulated energies of plasmons are transferred to electrons in the conduction band of the material, attributes to the efficient photocatalytic transformation. Mass spectrometric detection of intermediate radical anions and negative ions with stable isotope labeling unambiguously identifies that highly energetic hot electrons can escape from the plasmonic nanostructures, be collected by adsorbed molecules, and initiate bond cleavages. It was demonstrated that losses of two H atoms result in the anaerobic oxidization of each benzyl alcohol molecule to a benzyl aldehyde molecule in the absence of molecular oxygen with more than 90 % yields. The well recyclable plasmonic nanoreactors implicate the injection of transferred electrons eventually back to electronically depleted Au+ positive ions. Bridged by adsorbed molecules, electrons were repeatedly circulated back and forth in plasmonic nanoreactors, where the collected light was eventually converted into chemical energy.

Enantioselective Synthesis of Highly Substituted Fluoroalkylated Benzopyranones and 3-Coumaranones via N-Heterocyclic Carbene-Catalyzed Intramolecular Annulations.

A highly enantioselective intramolecular NHC-catalyzed approach for the synthesis of fluoroalkylated benzopyranones and 3-coumaranones with all-carbon quaternary stereocenters is presented. This reaction is catalyzed by N-heterocyclic carbenes (NHCs) and involves annulation reactions between in situ generated acyl anion intermediates and highly substituted trifluoromethyl-β,β-disubstituted Michael acceptors. The method can also be extended to perfluoroalkyl homologues.

The reaction of unprotected 1,4-dihydropyridine Hantzsch esters with Grignard reagents: Preparation of unsymmetrical 1,4-dihydropyridine derivatives

The mild bromine-magnesium exchange reaction using i-PrMgBr in THF on the 2-bromomethyl-1,4-dihydropyridine Hantzsch esters allowed the synthesis of highly functionalized magnesiated 1,4-dihydropyridines with ester groups tolerance. Treatment of the resulting anionic intermediates with hard electrophile methyl iodide gave N-methylated product 6 and pyridine derivative 7 in 60 % and 10 % yields, respectively. In trapping the reaction mixture of magnesiated 1,4-dihydropyridine with ethyl bromide, pyridine derivative 8, and dimer 9 were obtained. Also, FeCl3-catalyzed cross-coupling reaction of allylMgBr, i-PrMgBr, and n-BuMgBr Grignard reagents with 2-bromomethyl-1,4-dihydropyridine derivative 2 afforded unsymmetrical 1,4-dihydropyridine derivatives 10a-c in good yields.

Hydrogenation of S6-C60(CF3)12

The first results of the hydrogenation of S6-symmetric trifluoromethylfullerene C60(CF3)12 in two types of reactions were reported: (1) high-temperature radical hydrogenation with 9,10-dihydroanthracene and (2) nucleophilic hydrogenation with sodium tetraborohydride under mild conditions. The high-temperature radical hydrogenation of S6-C60(CF3)12 is accompanied by partial elimination of CF3 groups and leads to the formation of a complex mixture of products of a composition C60(CF3)8–12H18–22. During the hydrogenation of NaBH4 under mild conditions, selective formation of the hydride C60(CF3)12H12 was recorded by mass spectroscopy. A kinetic analysis of the sequential nucleophilic hydrogenation of S6-C60(CF3)12 was performed, using quantum-chemical modeling at the level of density functional theory, under the assumption of linear correlation between the activation energy and the enthalpy of elementary steps of the same type. The isomeric composition was predicted for the series of anionic intermediates C60(CF3)12H−2n−12−1− and their protonation products C60(CF3)12H2n, where n = 1–6. The hydrogenation of S6-C60(CF3)12 should lead to the formation of the thermodynamically and kinetically most stable product ortho-S6-C60(CF3)12H12, in which all hydrogen atoms are located in neighboring positions near the CF3 groups, forming together with them a near-equatorial belt of 24 addends while retaining the triphenylene fragments at two opposite poles. The average bond dissociation energy BDE(C–H) in ortho-S6-C60(CF3)12H12 is 298 kJ mol–1, which is approximately 20 kJ mol–1 higher than the BDE(C–H) of known fullerene hydrides C60H18 and C60H36 (PBE0/def2-SVP).

Direct Electrophilic Attack of Compound I on the Indole Ring in the Peroxygenase Mechanism of Dehaloperoxidase DHP B in Degrading Haloindole: Electron Transfer Promotes the Reaction.

The H2O2-dependent degradation of haloindole catalyzed by the dehaloperoxidase (DHP) from Amphitrite ornate has been reported to employ the peroxygenase mechanism, and the two oxidized products 5-halo-2-oxindole and 5-halo-3-oxindole have a similar amount. According to a previous experimental study, compound I (Cpd I) was suggested to be responsible for triggering the reaction, and the reaction may undergo three possible intermediates; however, the reaction details are still unclear. To clarify the reaction mechanism of DHP, the computational model was constructed on the basis of the high-resolution crystal structure, and a series of the quantum mechanical/molecular mechanical calculations were performed. Based on our calculation results, it is confirmed that the reaction starts from the direct electrophilic attack of Cpd I on the indole ring of the substrate, and the resulted intermediate contains both a carbocation and an oxygen anion, whereas the common hydrogen abstraction by Cpd I was calculated to correspond to a relatively higher barrier. In addition, a net electron transfer from the substrate to the iron center is observed during the attack of Cpd I on the indole ring; therefore, the carbocation/oxygen anion intermediate can easily undergo an intramolecular hydride transfer to form the product 5-halo-2-oxindole or isomerize to the epoxide intermediate which finally generates another product 5-halo-3-oxindole. It is the zwitterionic characteristic of the intermediate that makes the intermolecular hydride transfer quite easy, and it is the high electron affinity of the iron center that promotes the single-electron oxidation of the reaction intermediate. Our calculations well explain the formation of two oxidized products 5-halo-2-oxindole and 5-halo-3-oxindole.

Shining Fresh Light on Complex Photoredox Mechanisms through Isolation of Intermediate Radical Anions.

Photoredox catalysis (PRC) has gained enormous and wide-ranging interest in recent years but has also been subject to significant mechanistic uncertainty, even controversy. To provide a method by which the missing understanding can begin to be filled in, we demonstrate herein that it is possible to isolate as authentic materials the one-electron reduction products of representative PRC catalysts (PCs). Specifically, KC8 reduction of both 9,10-dicyanoanthracene and a naphthalene monoamide derivative in the presence of a cryptand provides convenient access to the corresponding [K(crypt)+][PC·-] salts as clean materials that can be fully characterized by techniques including EPR and XRD. Because PC·- states are key intermediates in PRC reactions, such isolation allows for highly controlled study of these anions' specific reactivity and hence their mechanistic roles. As a demonstration of this principle, we show that these salts can be used to conveniently interrogate the mechanisms of recent, high-profile "conPET" and "e-PRC" reactions, which are currently the subject of both significant interest and acute controversy. Using very simple experiments, we are able to provide striking insights into these reactions' underlying mechanisms and to observe surprising levels of hidden complexity that would otherwise have been very challenging to identify and that emphasize the care and control that are needed when interrogating and interpreting PRC mechanisms. These studies provide a foundation for the study of a far broader range of questions around conPET, e-PRC, and other PRC reaction mechanisms in the future, using the same strategy of PC·- isolation.

Deep Electroreductive Chemistry: Harnessing Carbon- and Silicon-based Reactive Intermediates in Organic Synthesis.

This Viewpoint outlines our recent contribution in electroreductive synthesis. Specifically, we leveraged deeply reducing potentials provided by electrochemistry to generate radical and anionic intermediates from readily available alkyl halides and chlorosilanes. Harnessing the distinct reactivities of radicals and anions, we have achieved several challenging transformations to construct C-C, C-Si, and Si-Si bonds. We highlight the mechanistic design principle that underpinned the development of each transformation and provide a view forward on future opportunities in growing area of reductive electrosynthesis.

A Sulfoxide Reagent for Sulfinylative Cross-Coupling

AbstractI recently documented the strategic use of a sulfoxide reagent as a sulfur monoxide equivalent to enable one-pot, three-component syntheses of sulfoxides and sulfinamides. The sulfoxide reagent donates the SO unit upon the reaction with Grignard reagents (RMgX) as sulfenate anions (RSO–). The anionic sulfur intermediates can be readily transformed into sulfoxides and sulfinamides via trapping with appropriate carbon and nitrogen electrophiles. This Synpacts article highlights my first efforts to establish a general sulfinylative cross-coupling platform.1 Introduction2 Development of a Sulfoxide Reagent as a Sulfur Monoxide Equivalent3 Conclusions and Future Directions

Sulfur-Containing Radical Anions Formed by Photolysis of Thiosulfate: Quantum-Chemical Analysis.

The photochemistry of sodium thiosulfate (S2O32-) in aqueous solutions is rather complicated. Several sulfur-containing radical anions are formed upon photoexcitation. Any of them are rather common (SO3•-, SO2•-, and SO5•-); others are rare (S2O3•-, •S4O63-, and S•-) or never documented (S2O5•-). In order to support the identification of intermediate radical anions, quantum-chemical (QM─quantum mechanical) calculations of the geometric and electronic structures of S2O3•-, S2O5•-, and •S4O63- were performed. Two different approaches, time-dependent density functional theory and complete active space self-consistent field, were applied to identify the method optimal for the reproduction of the experimental electronic absorption spectra. Several of the most commonly used functionals were considered. The best agreement with the experimentally observed spectra of reference compounds (common sulfur-containing anions and radical anions) was achieved for the WB97X-D3 functional. Using this approach, satisfactory agreement between experimental and calculated spectra of S2O3•-, S2O5•-, and •S4O63- was achieved. It was shown that S2O5•- and •S4O63- can exist in two isomeric forms with different spectral properties. These isomers are S2O3O2•-; SO3SO2•- for the case of S2O5•- and (S2O3)2•3-; (S3O32-...SO3•-) for the case of •S4O63-.

An Electrochemical Strategy to Synthesize Disilanes and Oligosilanes from Chlorosilanes.

Silanes are important compounds in industrial and synthetic chemistry. Here, we develop a general approach for the synthesis of disilanes as well as linear and cyclic oligosilanes via the reductive activation of readily available chlorosilanes. The efficient and selective generation of silyl anion intermediates, which are arduous to achieve by other means, allows for the synthesis of various novel oligosilanes by heterocoupling. In particular, this work presents a modular synthesis for a variety of functionalized cyclosilanes, which may give rise to materials with distinct properties from linear silanes but remain challenging synthetic targets. In comparison to the traditional Wurtz coupling, our method features milder conditions and improved chemoselectivity, broadening the functional groups that are compatible in oligosilane preparation. Computational studies support a mechanism whereby differential activation of sterically and electronically distinct chlorosilanes are achieved in an electrochemically driven radical-polar crossover mechanism.

An Electrochemical Strategy to Synthesize Disilanes and Oligosilanes from Chlorosilanes**

AbstractSilanes are important compounds in industrial and synthetic chemistry. Here, we develop a general approach for the synthesis of disilanes as well as linear and cyclic oligosilanes via the reductive activation of readily available chlorosilanes. The efficient and selective generation of silyl anion intermediates, which are arduous to achieve by other means, allows for the synthesis of various novel oligosilanes by heterocoupling. In particular, this work presents a modular synthesis for a variety of functionalized cyclosilanes, which may give rise to materials with distinct properties from linear silanes but remain challenging synthetic targets. In comparison to the traditional Wurtz coupling, our method features milder conditions and improved chemoselectivity, broadening the functional groups that are compatible in oligosilane preparation. Computational studies support a mechanism whereby differential activation of sterically and electronically distinct chlorosilanes are achieved in an electrochemically driven radical‐polar crossover mechanism.

Two-Dimensional Metal Coordination Polymer Derived Indium Nanosheet for Efficient Carbon Dioxide Reduction to Formate.

Main group indium materials have been known as promising electrocatalysts for two-electron-involved carbon dioxide reduction to produce formate, which is a key energy vector in many industrial reactions. However, the synthesis of two-dimensional (2D) monometallic nonlayered indium remains a great challenge. Here, we present a facile electrochemical reduction strategy to transform 2D indium coordination polymer into elemental indium nanosheets. In a customized flow cell, the reconstructed metallic indium exhibits a high Faradaic efficiency (FE) of 96.3% for formate with a maximum partial current density exceeding 360 mA cm-2 and negligible degradation after 140 h operation in 1 M KOH solution, outperforming the state-of-the-art indium-based electrocatalysts. Moreover, in and ex situ electrochemical analysis and characterizations demonstrate that the enhanced exposure of active sites and mass/charge transport at the CO2 gas-catalyst-electrolyte triple-phase interface and the restrained electrolyte flooding are contributing to producing and stabilizing carbon dioxide radical anion intermediates, thus leading to superior catalytic performance.

Site-selective Hydrogenation/Deuteration of Benzylic Olefins Enabled by Electroreduction Using Water.

We describe an operationally simple and user-friendly protocol that allows the site-selective hydrogenation and deuteration of di-, tri- and tetrasubstituted benzylic olefins by electroreduction while other groups prone to hydrogenation are present. The radical anionic intermediates react with the most inexpensive hydrogen/deuterium source H2 O/D2 O. Our method overcomes many limitations that arise from previously reported electroreductive hydrogenations. The applicability of this reaction is demonstrated by a broad substrate scope (>50 examples) that focuses on functional group tolerance and sites that are affected by metal-catalyzed hydrogenation (alkenes, alkynes, protecting groups).

Cascade Vinylation/8π-Electrocyclization and Cu(II)-Catalyzed Dehydrogenation toward Highly Stable Formally Antiaromatic Cycloheptatrienyl Anions

An approach to the synthesis of seven-membered systems via the chain elongation of nucleophilic propenes and subsequent 8π-electrocyclization is proposed. The cascade reaction yields either cycloheptadienes or bicycloheptenes, and the latter are formed via a 6π-electrocyclization of intermediate cycloheptadienyl anion which was proved to be reversible in a basic medium. The electrocyclic nature of the ring-closing reactions was supported by density functional theory and DLPNO/CCSD(T) calculations. Highly electron-deficient cycloheptatrienes can be obtained from cycloheptadienes or bicycloheptenes via oxidation either introduced into the cascade reaction or performed as a separate reaction, with the overall yield of up to 81%. The oxidation step was performed by means of a rarely encountered Cu(II)-catalyzed dehydrogenation of cycloheptadienes or bicycloheptenes, and so the reaction mechanism was proposed. Stable formally 8π-antiaromatic cycloheptatrienyl-anion containing compounds were obtained, and some correlations between their UV-vis spectra and the structure of the distorted cycloheptatrienyl-anion moiety were clarified. Additionally, a base-induced retro-[2 + 2]-cycloaddition in a bicycloheptene derivative gave cyanotetra(methoxycarbonyl)cyclopentadienyl cesium.

Catalytic Strategies and Mechanism Analysis Orbiting the Center of Critical Intermediates in Lignin Depolymerization

Lignin, as a precious resource given to mankind by nature with abundant functional aromatic structures, has drawn much attention in the recent decade from academia to industry worldwide, aiming at harvesting aromatic compounds from this abundant and renewable natural polymer resource. How to efficiently depolymerize lignin to easy-to-handle aromatic monomers is the precondition of lignin utilization. Many strategies/methods have been developed to effectively degrade lignin into monomers, such as the traditional methods of pyrolysis, gasification, liquid-phase reforming, solvolysis, chemical oxidation, hydrogenation, reduction, acidolysis, alkaline hydrolysis, alcoholysis, as well as the newly developed redox-neutral process, biocatalysis, and combinatorial strategies. Therefore, there is a strong demand to systemically summarize these developed strategies and methods and reveal the internal transformation principles of the lignin. Focusing on the topic of lignin depolymerization to aromatic chemicals, this review reorganizes and categorizes the strategies/methods according to their mechanisms, orbiting the center of critical intermediates during the lignin linkage transformation, which includes the critical anionic intermediates, cationic intermediates, organometallic intermediates, organic molecular intermediates, aryl cation radical intermediates, and neutral radical intermediates. The corresponding introduction involves the generation and the transformation chemistry of the critical intermediates via the corresponding C-H/O-H/C-C/C-O chemical bond transformations, leading to the cleavage of the C-C/C-O linkage bonds. Accompanying the brief introduction of lignin chemistry and the final concluding remarks and perspectives on lignin depolymerization, this review aims to provide a current research process of lignin depolymerization, which may provide useful suggestions for this vigorous research field.

Solvent isotope effects in the catalytic cycle of P450 CYP17A1: Computational modeling of the hydroxylation and lyase reactions

The catalytic cycle of the cytochromes P450 (CYP) requires two electrons from a protein redox partner and two protons from water to generate the main catalytic intermediate, a ferryl-oxo complex with π-cation on the heme porphyrin ring, termed Compound 1. The protonation steps are at least partially rate-limiting, therefore the steady-state rates of P450 catalysis are usually slower in deuterated solvent (D2O) by a factor of 1.5–3. However, in several P450 systems a pronounced inverse kinetic solvent isotope effect (KSIE ∼0.4–0.7) is observed, where the reaction is faster in D2O. This raises an important mechanistic question: Is this inverse solvent isotope effect compatible with Compound 1 catalyzed reactions, or is it indicative of another catalytic intermediate being involved? In this communication we use exhaustive numerical modeling of the P450 steady-state kinetics to demonstrate that a significant inverse KSIE cannot be obtained for a pure Compound 1 driven catalytic cycle of P450. Rather, an alternative, protonation independent, catalytic intermediate needs to be introduced. This result is applicable to the broad spectrum of P450s in nature, but as an example we use the extensively documented inverse isotope effect in the human steroid biosynthetic P450 CYP17A1 where the involvement of a heme peroxo anion intermediate has been characterized. Based on this analysis, we show that the observation of an inverse KSIE can be used as a general mechanistic probe for reaction cycle intermediates in the cytochromes P450.

Two‐Step Redox in Polyimide: Witness by In Situ Electron Paramagnetic Resonance in Lithium‐ion Batteries

AbstractOrganic materials are promising candidates for future rechargeable batteries, owing to their high natural abundance and rapidly redox reaction. Elaborating the charge/discharge process of organic electrode is critical to unveil the fundamental redox mechanism of lithium‐ion batteries (LIBs), but monitoring of this process is still challenging. Here, we report a nondestructive electron paramagnetic resonance (EPR) technique to real‐time detect the electron migration step within polyimide cathode. From in situ EPR tests, we vividly observe a classical redox reaction along with two‐electron transfer which only shows one pair of peaks in the cyclic voltammetry curve. The radical anion and dianion intermediates are detailed delineation at redox sites in EPR spectra, which can be further confirmed through density functional theory calculations. This approach is especially crucial to elaborate the correlation behind electrochemical and molecular structure for multistep organic‐based LIBs.