Electron-deficient Arenes Research Articles

A Fluorinated Imide-Functionalized Arene Enabling a Wide Bandgap Polymer Donor for Record-Efficiency All-Polymer Solar Cells.

All-polymer solar cells (all-PSCs) present compelling advantages for commercial applications, including mechanical durability and optical and thermal stability. However, progress in developing high-performance polymer donors has trailed behind the emergence of excellent polymer acceptors. In this study, we report a new electron-deficient arene, fluorinated bithiophene imide (F-BTI) and its polymer donor SA1, in which two fluorine atoms are introduced at the outer β-positions in the thiophene rings of BTI to fine-tune the energy levels and aggregation of the resulting polymers. SA1 exhibits a deep HOMO level of -5.51 eV, a wide bandgap of 1.81 eV and suitable miscibility with the polymer acceptor. Polymer chains incorporating F-BTI result in a highly ordered π-π stacking and favorable phase-separated morphology within the all-polymer active layer. Thus, SA1 : PY-IT-based all-PSCs exhibit an efficiency of 16.31 % with excellent stability, which is further enhanced to a record value of 19.33 % (certified: 19.17 %) by constructing ternary device. This work demonstrates that F-BTI offers an effective route for developing new polymer materials with improved optoelectronic properties, and the emergence of F-BTI will change the scenario in terms of developing polymer donor for high-performance and stable all-PSCs.

Enantioselective Synthesis of α-Aryl Ketones by a Cobalt-Catalyzed Semipinacol Rearrangement.

A highly enantioselective cobalt-catalyzed semipinacol rearrangement of symmetric α,α-diarylallylic alcohols is disclosed. A chiral cobalt-salen catalyst generates a highly electrophilic carbocation surrogate following hydrogen atom transfer and radical-polar crossover steps. This methodology provides access to enantioenriched α-aryl ketones through invertive displacement of a cobalt(IV) complex during 1,2-aryl migration. A combination of readily available reagents, silane and N-fluoropyridinium oxidant, are used to confer this type of reactivity. An exploration into the effect of aryl substitution revealed the reaction tolerates para- and meta-halogenated, mildly electron-rich and electron-poor aromatic rings with excellent enantioselectivities and yields. The yield of the rearrangement diminished with highly electron-rich aryl rings whereas very electron-deficient and ortho-substituted arenes led to poor enantiocontrol. A Hammett analysis demonstrated the migratory preference for electron-rich aromatic rings, which is consistent with the intermediacy of a phenonium cation.

Rapid Electrophilic 211At-Astatination of Trimethylgermyl Arenes.

A set of 211At-astatoarenes were synthesized from corresponding trimethylgermyl arenes with an average radiochemical conversion (RCC) of ca. 50 % for electron-rich and approx. 70 % in case of electron-deficient arenes. Both electron rich and electron poor substrates were successfully radiolabeled at room temperature (RT) using relatively low precursor amounts (0.15 μmol/0.02 mL solvent (7.5 mM)). Ready access to ortho-, para- and meta- astatinated arenes was achievable. Optimized reaction conditions were successfully applied to label a poly (ADP-ribose) polymerase (PARP) inhibitor with a RCC of approx. 50 %. We believe that trimethylgermyl derivatives are a viable addition to the astatination precursor toolbox and facilitate astatination of arenes. The developed labeling method should easily be applicable for productions under good manufacturing practice (GMP).

Selective Mono-Defluorinative Cross-Coupling of Trifluoromethyl arenes via Multiphoton Photoredox Catalysis.

A new cross-coupling of trifluoromethyl arenes has been realized via multiphoton photoredox catalysis. Trifluoromethyl arenes were demonstrated to undergo selective mono-defluorinative alkylation under mild reaction conditions providing access to a series of valuable α,α-difluorobenzylic compounds. The reaction shows broad substrate scope and general functional group tolerance. In addition to the electron-deficient trifluoromethyl arenes that are easily reduced to the corresponding radical anion, more challenging electron-rich substrates were also successfully applied. Steady-State Stern-Volmer quenching studies indicated that the trifluoromethyl arenes were reduced by the multiphoton excited Ir-based photocatalyst.

Mechanochemical Birch Reduction with Low Reactive Alkaline Earth Metals.

Birch reduction and similar dissolved metal-type transformations hold significant importance in the organic synthesis toolbox. Historically, the field has been dominated by alkali metal reductants. In this study, we report that largely neglected, low-reactive alkaline earth metals can become powerful and affordable reductants when used in a ball mill under essentially solvent-free conditions, in the presence of ethylenediamine and THF as liquid additives. Calcium can reduce both electron-deficient and electron-rich arenes, with yields of products similar to those obtained with lithium metal. Magnesium reveals enhanced reducing power, enabling the reduction of benzoic acids while keeping electron-rich aromatic moieties intact and allows for chemoselective transformations. The developed mechanochemical approach uses readily available and safer-to-handle metals, operates under air and ambient temperature conditions, and can be used for gram-scale preparations. Finally, we demonstrate that the developed conditions can be used for other dissolved metal-type reductive transformations, including reductive amination, deoxygenation, dehalogenation, alkene and alkyne reductions.

Electrochemically Driven para-Selective C(sp2)-H Alkylation Enabled by Activation of Alkyl Halides without Sacrificial Anodes.

With alkyl halides (I, Br, Cl) as a coupling partner, an electrochemically driven strategy for para-selective C(sp2)-H alkylation of electron-deficient arenes (aryl esters, aldehydes, nitriles, and ketones) has been achieved to access diverse alkylated arenes in one step. The reaction enables the activation of alkyl halides in the absence of sacrificial anodes, achieving the formation of C(sp2)-C(sp3) bonds under mild electrolytic conditions. The utility of this protocol is reflected in high site selectivity, broad substrate scope, and scalable.

Catalytic thiolation-depolymerization-like decomposition of oxyphenylene-type super engineering plastics via selective carbon–oxygen main chain cleavages

As the effective use of carbon resources has become a pressing societal issue, the importance of chemical recycling of plastics has increased. The catalytic chemical decomposition for plastics is a promising approach for creating valuable products under efficient and mild conditions. Although several commodity and engineering plastics have been applied, the decompositions of stable resins composed of strong main chains such as polyamides, thermoset resins, and super engineering plastics are underdeveloped. Especially, super engineering plastics that have high heat resistance, chemical resistance, and low solubility are nearly unexplored. In addition, many super engineering plastics are composed of robust aromatic ethers, which are difficult to cleave. Herein, we report the catalytic depolymerization-like chemical decomposition of oxyphenylene-based super engineering plastics such as polyetheretherketone and polysulfone using thiols via selective carbon–oxygen main chain cleavage to form electron-deficient arenes with sulfur functional groups and bisphenols. The catalyst combination of a bulky phosphazene base P4-tBu with inorganic bases such as tripotassium phosphate enabled smooth decomposition. This method could be utilized with carbon- or glass fiber-enforced polyetheretherketone materials and a consumer resin. The sulfur functional groups in one product could be transformed to amino and sulfonium groups and fluorine by using suitable catalysts.

1,7-Hydride transfer-involved dearomatization of quinolines to access C3-spiro hydroquinolines

1,7-Hydride transfer-involved dearomatization of quinolines toward C3-spiro hydroquinoline derivatives has been developed. This method offers a protocol to achieve the dearomatization of electron-deficient arenes via the redox-neutral hydride transfer process. A series of C3-spiro hydroquinolines can be provided in moderate to excellent yields (up to 98%) with good diastereoselectivities. Significant advantages such as high step- and atom-economy, as well as redox-neutral and mild conditions, make it an appealing alternative to achieve the dearomatization of quinolines.

Dicationic Acridinium/Carbene Hybrids as Strongly Oxidizing Photocatalysts.

A new design concept for organic, strongly oxidizing photocatalysts is described based upon dicationic acridinium/carbene hybrids. A highly modular synthesis of such hybrids is presented, and the dications are utilized as novel, tailor-made photoredox catalysts in the direct oxidative C-N coupling. Under optimized conditions, benzene and even electron-deficient arenes can be oxidized and coupled with a range of N-heterocycles in high to excellent yields with a single low-energy photon per catalytic turnover, while commonly used acridinium photocatalysts are not able to perform the challenging oxidation step. In contrast to traditional photocatalysts, the hybrid photocatalysts reported here feature a reversible two-electron redox system with regular or inverted redox potentials for the two-electron transfer. The different oxidation states could be isolated and structurally characterized supported by NMR, EPR, and X-ray analysis. Mechanistic experiments employing time-resolved emission and transient absorption spectroscopy unambiguously reveal the outstanding excited-state potential of our best-performing catalyst (+2.5 V vs SCE), and they provide evidence for mechanistic key steps and intermediates.

Transition-Metal-Free, Reductive Csp2-Csp3 Bond Constructions via Electrochemically Induced Alkyl Radicals.

Construction of the Csp2-Csp3 bond without the aid of transition metal catalysts has been achieved by coupling the electrogenerated alkyl radicals with electron deficient (hetero)arenes in an undivided cell. Simultaneous cathodic reduction of both unactivated alkyl halides and cyanobenzenes under high potential enables radical-radical cross-coupling to deliver alkylarenes in the absence of transition metals. Depending on the coupling partner, the electrogenerated alkyl radicals can also proceed the Minisci-type reaction with N-heteroarenes without redox agents.

15NRORC: An Azine Labeling Protocol.

A practical method for the synthesis of 15N-labeled azines with a high degree of isotopic enrichment is described. Activation of azine heterocycles with an electron-deficient arene allows for the facile substitution of the nitrogen atom with a specifically designed 15N-labeled reagent that undergoes a canonical ANRORC-type mechanism. A wide range of azines can be converted to their corresponding 15N isotopologs using this method, and it also allows for dearomative access to reduced heterocyclic congeners. A short dearomative formal synthesis of 15N-solifenacin is accomplished as well to demonstrate a practical application of this method for generating labeled pharmaceuticals.

Palladium-Catalyzed Electrooxidative Double C-H Arylation.

The electrochemical transition metal-catalyzed cross-dehydrogenative reaction has emerged as a promising platform to achieve a sustainable and atom-economic organic synthesis that avoids hazardous oxidants and minimizes undesired byproducts and circuitous functional group operations. However, a poor mechanistic understanding still prevents the widespread adoption of this strategy. In this regard, we herein present an electrochemical palladium-catalyzed oxidative coupling strategy to access biaryls in the absence of a stoichiometric chemical oxidant. The robust palladaelectrocatalysis considerably suppresses the occurrence of homocoupling and oxygenation, being compatible even with electron-deficient arenes. Late-stage functionalization and Boscalid precursor synthesis further highlighted the practical importance of our electrolysis. Remarkably, mechanistic studies including the evaluation of the reaction order of each component by variable time normalization analysis (VTNA) and initial rate analysis, H/D exchange experiment, kinetic isotope effect, and stoichiometric organometallic experiments provided strong support for the involvement of transmetalation between two organopalladium complexes in the turnover limiting step. Therefore, matching the concentrations or lifetimes of two distinct organopalladium intermediates is revealed to be a pivot to the success of electrooxidative catalysis. Moreover, the presence of cationic copper(II) seems to contribute to the stabilization of the palladium(0) catalyst instead of playing a role in the oxidation of the catalyst.

Electron-Poor Acridones and Acridiniums as Super Photooxidants in Molecular Photoelectrochemistry by Unusual Mechanisms.

Electron-deficient acridones and in situ generated acridinium salts are reported as potent, closed-shell photooxidants that undergo surprising mechanisms. When bridging acyclic triarylamine catalysts with a carbonyl group (acridones), this completely diverts their behavior away from open-shell, radical cationic, 'beyond diffusion' photocatalysis to closed-shell, neutral, diffusion-controlled photocatalysis. Brønsted acid activation of acridones dramatically increases excited state oxidation power (by +0.8 V). Upon reduction of protonated acridones, they transform to electron-deficient acridinium salts as even more potent photooxidants (*E1/2 =+2.56-3.05 V vs SCE). These oxidize even electron-deficient arenes where conventional acridinium salt photooxidants have thusfar been limited to electron-rich arenes. Surprisingly, upon photoexcitation these electron-deficient acridinium salts appear to undergo two electron reductive quenching to form acridinide anions, spectroscopically-detected as their protonated forms. This new behaviour is partly enabled by a catalyst preassembly with the arene, and contrasts to conventional SET reductive quenching of acridinium salts. Critically, this study illustrates how redox active chromophoric molecules initially considered photocatalysts can transform during the reaction to catalytically active species with completely different redox and spectroscopic properties.

Nucleophilic Carbenes Derived from Dichloromethane.

Nickel PyBox catalysts promote nucleophilic cyclopropanation reactions using CH2 Cl2 as a methylene source and Mn as a stoichiometric reductant. The substrate scope includes a broad range of alkenes bearing electron-withdrawing substituents, including esters, amides, ketones, nitriles, sulfones, phosphonate esters, trifluoromethyl groups, and electron-deficient arenes. Enantioselective cyclopropanations of α,β-unsaturated esters have been developed using chiral PyBox ligands. Mechanistic studies suggest the intermediacy of a (PyBox)Ni=CH2 species, which adds to the alkene by a stepwise [2+2]-cycloaddition/C-C reductive elimination mechanism. DFT models provide a rationale for the nucleophilic character of the nickel carbene and the sense of enantioinduction.

Electrocatalyzed direct arene alkenylations without directing groups for selective late-stage drug diversification

Electrooxidation has emerged as an increasingly viable platform in molecular syntheses that can avoid stoichiometric chemical redox agents. Despite major progress in electrochemical C−H activations, these arene functionalizations generally require directing groups to enable the C−H activation. The installation and removal of these directing groups call for additional synthesis steps, which jeopardizes the inherent efficacy of the electrochemical C−H activation approach, leading to undesired waste with reduced step and atom economy. In sharp contrast, herein we present palladium-electrochemical C−H olefinations of simple arenes devoid of exogenous directing groups. The robust electrocatalysis protocol proved amenable to a wide range of both electron-rich and electron-deficient arenes under exceedingly mild reaction conditions, avoiding chemical oxidants. This study points to an interesting approach of two electrochemical transformations for the success of outstanding levels of position-selectivities in direct olefinations of electron-rich anisoles. A physical organic parameter-based machine learning model was developed to predict position-selectivity in electrochemical C−H olefinations. Furthermore, late-stage functionalizations set the stage for the direct C−H olefinations of structurally complex pharmaceutically relevant compounds, thereby avoiding protection and directing group manipulations.

Pd(II) and Rh(I) Catalytic Precursors for Arene Alkenylation: Comparative Evaluation of Reactivity and Mechanism Based on Experimental and Computational Studies.

We combine experimental and computational investigations to compare and understand catalytic arene alkenylation using the Pd(II) and Rh(I) precursors Pd(OAc)2 and [(η2-C2H4)2Rh(μ-OAc)]2 with arene, olefin, and Cu(II) carboxylate at elevated temperatures (>120 °C). Under specific conditions, previous computational and experimental efforts have identified heterotrimetallic cyclic PdCu2(η2-C2H4)3(μ-OPiv)6 and [(η2-C2H4)2Rh(μ-OPiv)2]2(μ-Cu) (OPiv = pivalate) species as likely active catalysts for these processes. Further studies of catalyst speciation suggest a complicated equilibrium between Cu(II)-containing complexes containing one Rh or Pd atom with complexes containing two Rh or Pd atoms. At 120 °C, Rh catalysis produces styrene >20-fold more rapidly than Pd. Also, at 120 °C, Rh is ∼98% selective for styrene formation, while Pd is ∼82% selective. Our studies indicate that Pd catalysis has a higher predilection toward olefin functionalization to form undesired vinyl ester, while Rh catalysis is more selective for arene/olefin coupling. However, at elevated temperatures, Pd converts vinyl ester and arene to vinyl arene, which is proposed to occur through low-valent Pd(0) clusters that are formed in situ. Regardless of arene functionality, the regioselectivity for alkenylation of mono-substituted arenes with the Rh catalyst gives an approximate 2:1 meta/para ratio with minimal ortho C-H activation. In contrast, Pd selectivity is significantly influenced by arene electronics, with electron-rich arenes giving an approximate 1:2:2 ortho/meta/para ratio, while the electron-deficient (α,α,α)-trifluorotoluene gives a 3:1 meta/para ratio with minimal ortho functionalization. Kinetic intermolecular arene ethenylation competition experiments find that Rh reacts most rapidly with benzene, and the rate of mono-substituted arene alkenylation does not correlate with arene electronics. In contrast, with Pd catalysis, electron-rich arenes react more rapidly than benzene, while electron-deficient arenes react less rapidly than benzene. These experimental findings, in combination with computational results, are consistent with the arene C-H activation step for Pd catalysis involving significant η1-arenium character due to Pd-mediated electrophilic aromatic substitution character. In contrast, the mechanism for Rh catalysis is not sensitive to arene-substituent electronics, which we propose indicates less electrophilic aromatic substitution character for the Rh-mediated arene C-H activation.

Para-Selective, Direct C(sp2)-H Alkylation of Electron-Deficient Arenes by the Electroreduction Process.

Direct para-selective C(sp2)-H alkylation of electron-deficient arenes based on the electroreduction-enabled radical addition of alkyl bromides has been developed under mild conditions. In the absence of any metals and redox agents, the simple electrolysis system tolerates a variety of primary, secondary, and tertiary alkyl bromides and behaves as an important complement to the directed alkylation of the C(sp2)-H bond and the classic Friedel-Crafts alkylation. This electroreduction process provides a more straightforward, environmentally benign, and effective alkylation method for electron-deficient arenes.

Cooperative Friedel-Crafts Alkylation of Electron-Deficient Arenes via Catalyst Activation with Hexafluoroisopropanol.

A Friedel-Crafts alkylation of electron-deficient arenes with aldehydes through ''catalyst activation'' is presented. Through hydrogen bonding interactions, the solvent 1,1,1,3,3,3, -hexafluoroisopropanol (HFIP) interacted with the added Brønsted acid catalyst pTSA•H2 O, increasing its acidity. This activated catalyst enabled the Friedel-Crafts alkylation of electron-neutral as well as electron-deficient arenes. Strongly electron withdrawing arenes including arenes with multiple halogen atoms, NO2 , CHO, CO2 R, and CN, groups acted as efficient nucleophiles in this reaction. DFT studies reveal multiple roles of solvent HFIP viz; increasing the Brønsted acidity of the catalyst pTSA•H2 O, and stabilization of the transition states through a concerted pathway enabling the challenging reaction.

Enantioselective transition-metal catalysis via an anion-binding approach.

Asymmetric transition-metal catalysis represents a powerful strategy for accessing enantiomerically enriched molecules1-3. The classical strategy for inducing enantioselectivity with transition-metal catalysts relies on direct complexation of chiral ligands to produce a sterically constrained reactive metal site that allows formation of the major product enantiomer while effectively inhibiting the pathway to the minor enantiomer through steric repulsion4. The chiral-ligand strategy has proven applicable to a wide variety of highly enantioselective transition-metal-catalysed reactions, but important scenarios exist that impose limits to its successful adaptation. Here, we report a new approach for inducing enantioselectivity in transition-metal-catalysed reactions that relies on neutral hydrogen-bond donors (HBDs)5,6 that bind anions of cationic transition-metal complexes to achieve enantiocontrol and rate enhancement through ion pairing together with other non-covalent interactions7-9. A cooperative anion-binding effect of a chiral bis-thiourea HBD is demonstrated to lead to high enantioselectivity (up to 99% enantiomeric excess) in intramolecular ruthenium-catalysed propargylic substitution reactions10. Experimental and computational mechanistic studies show the attractive interactions between electron-deficient arene components of the HBD and the metal complex that underlie enantioinduction and the acceleration effect.

Electrochemical deoxygenative arylation of aldehydes and ketones.

The construction of diaryl alkanes from aromatic aldehydes or ketones with electron-deficient arenes is achieved in the presence of trivalent phosphine under electrochemical conditions. Reductive coupling between electron-deficient arenes and the carbonyl groups of aldehydes or ketones occurs at the cathode to yield diaryl alcohols. At the anode, the trivalent phosphine reagent may undergo single-electron oxidation to generate its radical cation, which reacts with the diaryl alcohols to form dehydroxylated products.