Redox-neutral Reaction Research Articles

Beyond Kolbe and Hofer-Moest: Electrochemical Synthesis of Carboxylic Anhydrides from Carboxylic Acids.

Herein we report a conceptually new non‐decarboxylative electrolysis of carboxylic acids to obtain their corresponding anhydrides as highly valuable reagents in organic synthesis. All carbon atoms of the starting material are preserved in the product in an overall redox‐neutral reaction. In a broad substrate scope of carboxylic acids the anhydrides are generated with high selectivity, which demonstrates the versatility of the developed method. Beneficially, no dehydrating reagents are required in comparison to conventional methods and the synthesis is based on uncritical starting materials using graphite and stainless steel as very inexpensive and eco‐friendly electrode materials.

Near-infrared light photocatalysis enabled by a ruthenium complex-integrated metal–organic framework via two-photon absorption

SummaryPhotocatalysis under UV/visible light irradiation has emerged as one of the green methodologies for solar energy utilization and organic synthesis. These photocatalytic processes are typically initiated by one-photon-absorbing metal complexes or organic dyes. Nevertheless, the intrinsic restrictions of UV/visible light irradiation, such as shallow penetration in reaction solutions, competing absorption by substrates, and limited coverage of the solar spectrum, call for the development of innovative photocatalysts functioning under longer wavelength irradiation. Herein, we report a ruthenium complex containing a metal-organic framework, MOF-Ru1, which can drive diverse organic reactions under 740 nm light irradiation following the two-photon absorption (TPA) process. Various organic transformations such as energy transfer, reductive, oxidative, and redox neutral reactions were realized using this heterogeneous hybrid photocatalyst. Overall, MOF-Ru1 represents an intriguing TPA photocatalyst active under near-infrared light irradiation, paving a way for the efficient utilization of low-energy light and convenient photocatalyst recycling because of phase separation.

Visible‐light‐promoted Radical Cyclization/Arylation Cascade for the Construction of α,α‐Difluoro‐γ‐Lactam‐Fused Quinoxalin‐2(1H)‐Ones

Comprehensive SummaryA visible‐light‐induced tandem radical intramolecular cyclization/arylation of quinoxalin‐2(1H)‐ones with bromodifluoroacetamides is described. This protocol allows efficient access to a variety of valuable α,α‐difluoro‐γ‐lactam‐fused quinoxalin‐2(1H)‐ones in moderate to good yields under metal‐free, mild and redox neutral reaction conditions. This strategy is tolerant of various functional groups and a broad range of substrates. The mechanism experiments suggested an involvement of 5‐exo‐trig cyclization and a radical process in this transformation.

Rhodium(iii)-catalyzed successive C(sp2)–H and C(sp2)–C(sp2) bond activation of aryl oximes: synthetic and mechanistic studies

A rhodium(iii)-catalyzed redox-neutral reaction of aryl oximes and internal alkynes to generate novel N-(2-cyanoaryl) indanone imines.

Synthesis of Functionalized Quinazolinones via Acid‐Catalyzed Redox Neutral Reaction

AbstractAn intramolecular 1,5‐hydride transfer reaction is observed during the synthesis of quinazolinones from anthranilamide and aliphatic dialdehyde under a mild acidic condition at room temperature. The hydride is being transferred from a dihydroquinazolinone moiety to a distal imine functional group. We proposed the hydride transfer mechanism based on the product obtained in a deuterated solvent. The influence of steric and electronic effects, and length of the dialdehyde towards the hydride transfer reaction, have been investigated. NMR and mass spectrometry are used to characterize the synthesized quinazolinones. This simple method is suitable for the preparation of a diverse array of multivalent quinazolinones.

Quantum Dot Photocatalysts for Organic Transformations.

Quantum dots (QDs) with tunable photo-optical properties and colloidal nature are ideal for a wide range of photocatalytic reactions. In particular, QD photocatalysts for organic transformations can provide new and effective synthetic routes to high value-added molecules under mild conditions. In this Perspective, we discuss the advances of employing QDs for visible-light-driven organic transformations categorized into net reductive reactions, net oxidative reactions, and redox neutral reactions. We then provide our outlook for potential future directions in the field: nanostructure engineering to improve charge separation efficiencies, ligand shell engineering to optimize overall catalyst performance, in situ comprehensive studies to delineate underlying reaction mechanisms, and laboratory automation with the assistance of modern computing techniques to revolutionize the reaction optimization process.

Efficient Redox-Neutral Photocatalytic Formate to Carbon Monoxide Conversion Enabled by Long-Range Hot Electron Transfer from Mn-Doped Quantum Dots.

Energetic hot electrons generated in Mn-doped quantum dots (QDs) via exciton-to-hot-electron upconversion possess long-range transfer capability. The long-range hot electron transfer allowed for superior efficiency in various photocatalytic reduction reactions compared to conventional QDs, which solely rely on the transfer of band edge electrons. Here we show that the synergistic action of the interfacial hole transfer to the initial reactant and subsequent long-range hot electron transfer to an intermediate species enables highly efficient redox-neutral photocatalytic reactions, thereby extending the benefits of Mn-doped QDs beyond reduction reactions. The photocatalytic conversion of formate (HCOO-) to carbon monoxide (CO), which is an important route to obtain a key component of syngas from an abundant source, is an exemplary redox-neutral reaction that exhibits a drastic enhancement of catalytic efficiency by Mn-doped QDs. Mn-doped QDs increased the formate to CO conversion rate by 2 orders of magnitude compared to conventional QDs with high selectivity. Spectroscopic study of charge transfer processes and the computational study of reaction intermediates revealed the critical role of long-range hot electron transfer to an intermediate species lacking binding affinity to the QD surface for efficient CO production. Specifically, we find that the formate radical (HCOO)•, formed after the initial hole transfer from the QD to HCOO-, undergoes isomerization to the (HOCO)• radical that subsequently is reduced to yield CO and OH-. Long-range hot electron transfer is particularly effective for reducing the nonbinding (HOCO)• radical, resulting in the large enhancement of CO production by overcoming the limitation of interfacial electron transfer.

Nickel-Catalyzed Reductive Asymmetric Aryl-Acylation and Aryl-Carbamoylation of Unactivated Alkenes

Nickel-Catalyzed Reductive Asymmetric Aryl-Acylation and Aryl-Carbamoylation of Unactivated Alkenes

Catalysis of Redox-Neutral Reactions By Electron Exchange between Electrodes and Organic Compounds

To most chemists the term ‘electrocatalysis’ is known as the facilitation of a heterogeneous electron transfer via a chemical interaction between the electrode and a substrate [1]. The opposite case, the utilization of a heterogeneous electron exchange to catalyze a chemical reaction (‘electrochemical catalysis’), is a much less known but yet a very powerful approach in electrosynthesis [2]. Here, the injection (or removal) of an electron into (or from) a substrate triggers a redox-neutral reaction (e.g. a molecular rearrangement) that may otherwise require harsh conditions and/or the use of reagents. Such processes involve the electrogeneration of an ionic or radical ionic species, which after a coupled chemical step either undergoes a backward electron exchange with the electrode (ECEb mechanism) or triggers a chain process in the bulk solution. Under these circumstances, sub-stoichiometric amounts of charge are sufficient to achieve a full conversion and conceptionally, the electrons and holes can be understood as being catalysts.In this contribution, the concept of electrochemical catalysis will be illustrated using the Newman-Kwart rearrangement (NKR) of O-aryl thiocarbamates 2 to the corresponding S-aryl compounds 3 as an example (see scheme below) [3]. Generally, the NKR represents the key-reaction in the three-step synthesis of thiophenols 4 from phenols 1 and proceeds between 200 and 300 °C [3]. Electrochemical catalysis, however, allows for operation at room temperature and provides a complementary reactivity with respect to the arene substitution [3,4]. The results of batch and flow electrolysis will be presented, along with a detailed mechanistic analysis based on cyclic voltammetry studies, control experiments, and quantum chemical calculations.

Tandem photoelectrochemical and photoredox catalysis for efficient and selective aryl halides functionalization by solar energy

Tandem photoelectrochemical and photoredox catalysis for efficient and selective aryl halides functionalization by solar energy

Dual Ni/photoredox-catalyzed asymmetric cross-coupling to access chiral benzylic boronic esters

The flourishing Ni/photoredox-catalyzed asymmetric couplings typically rely on redox-neutral reactions. In this work, we report a reductive cross-coupling of aryl iodides and α-chloroboranes under a dual catalytic regime to further enrich the metallaphotoredox chemistry. This approach proceeds under mild conditions (visible light, ambient temperature, no strong base) to access the versatile benzylic boronic esters with good functional group tolerance and excellent enantioselectivities.

Ruthenium catalyzed α-methylation of sulfones with methanol as a sustainable C1 source

Methylation of sulfones bearing an α-CH bond can be easily achieved via a one-step, Ru(ii) catalyzed redox neutral reaction using methanol as a sustainable C1 building block.

Mechanistic Studies on TiO2 Photoelectrochemical Radical Cation [2 + 2] Cycloadditions

In addition to electrochemical and photochemical approaches, the photoelectrochemical method using semiconductors as photoelectrodes is a third type of approach in the field of synthetic organic chemistry that enables precise control of single electron transfer (SET) reactions. Herein, we report mechanistic studies on TiO2 photoelectrochemical redox neutral reactions, where both reductive and oxidative SET are involved, using radical cation [2 + 2] cycloadditions as models. In the presence of platinum nanoparticles or molecular oxygen as electron sink or electron acceptor, respectively, the mechanistic details for the photoelectrochemical reactions can be investigated because the excited electron at the conduction band of TiO2 is removed.

Understanding the Difference between Electrochemical and Photochemical Single Electron Transfer: Investigation of Radical Cation [2 + 2] Cycloadditions

Chemical synthesis by electrocatalysis and photocatalysis has been developed as a new energy conversion system and it can realize sustainable production processes for various products. Electron transfer is driven by electrical energy and solar energy under ambient temperature and pressure. In the case of electrocatalysis, voltage and current are tunable, and it can realize easy control of reaction conditions. In photocatalysis with semiconductor nanoparticles, one particle can work as both oxidant and reductant, and it would be beneficial toward redox neutral reactions. To understand mechanistic details of both electrocatalysis and photocatalysis is important to develop new processes with high efficiency. We reported oxidative single electron transfer (SET) triggered radical cation cycloaddition reactions in lithium perchlorate (LiClO4)/nitromethane (CH3NO2) by electrolysis and TiO2 semiconductor photocatalysis. These reactions start by substrate activation to form radical cation species, which is derived from anodic oxidation (in electrolysis) or hole oxidation (in photocatalysis). In this research, the [2+2] cycloaddition reactions in LiClO4/CH3NO2 solution were used as model reactions to study mechanistic details of three different SET catalysis, including electrocatalysis TiO2 photocatalysis with and without Pt loading. TiO2 and Pt loaded TiO2 (Pt-TiO2) were selected as photocatalyst in this work. Commercially available TiO2 nanoparticles (P25, 20–40 nm) were used. Pt-TiO2 was synthesized from the TiO2 (P25) and H2PtCl6 as a Pt precursor. H2PtCl6 was reduced by NaBH4 in the presence of TiO2 in H2O to give Pt-TiO2. From TEM observations and EDS measurement, Pt nanoparticles were located on the surface of TiO2 with 3.8 wt% of loading ratio and the size was 2.9 nm. Two types of model [2+2] cycloaddition reactions were used in this research. One is reaction between enol ether and olefin, the other is reaction between enyloxy benzene and olefin. All reactions were carried out in 1 mol/L LiClO4/CH3NO2 solution. For electrocatalysis, constant potential (1.2 V, 1.0 F/mol) was used with carbon felt electrodes as both anode and cathode. For photocatalysis, TiO2 or Pt-TiO2 nanoparticles were dispersed in the solution with 10 mg/mL and the solution was irradiated by 15 W UV lamp. From cyclic voltammetry (CV) of substrate, it was indicated these reactions were driven by SET of enol ether or enyloxy benzene. In the case of enol ether model reaction under air, yield of cyclobutane product was similar to electrocatalysis (78%) and TiO2 photocatalysis (79%), however, Pt-TiO2 photocatalysis showed relatively low yield (46%). Previously, it was proposed that Pt can function as an electron trap to alter the mechanism of reductive SET. It could be explained that the reductive SET from Pt was not involved in the reaction, decreasing the yield of the product. In the case of enyloxy benzene model reaction under air, electrocatalysis realized high yield of cyclobutane product (81%), however, TiO2 and Pt-TiO2 photocatalysis showed low yields (53% and 17%, receptively). We found that O2 bubbling to solution improved the yield of the product when TiO2 photocatalysis (80%) was used, in contrast, it was not the case for the reaction using Pt-TiO2 photocatalysis (trace). It was indicated that O2 can work as a mediator or an oxidant and this role is important for the [2+2] cycloaddition between enyloxy benzene and olefin when TiO2 photocatalysis was used, however, it was not observed under Pt-TiO2 condition. One possibility is that, O2 functions as a reductive redox mediator. Specifically, O2 was reduced by excited electron in TiO2 conduction band via single electron reduction and superoxide species were generated. Since these species have high reducing ability, they can reduce cyclobutane intermediate radical cation to form cyclobutane product. In the case of Pt-TiO2, excited electron could be trapped by Pt, which altered the reductive SET from one-electron mechanism to two- or four-electron pathways that produced H2O2 or H2O from O2. Since these species cannot reduce the radical cation, cyclobutane product was not formed. In addition, H2O2 can change to OH radical species that have high oxidative potential and they potentially decomposed substrate and/or product. In conclusion, we demonstrated the mechanistic differences among electrocatalysis and TiO2 in the presence or absence of Pt by using SET triggered [2+2] cycloaddition reactions as models. Pt-TiO2 might decrease the reduction ability of TiO2. O2 bubbling can increase yield of product in enyloxy benzene reaction because superoxide species might be generated by excited electron in TiO2 and they function as a redox mediator to reduce radical cation intermediate. This O2 mediated system cannot be realized when Pt-TiO2 was used, probably because Pt can reduce O2 into H2O2 or H2O. Figure 1

Pd-Catalyzed Redox-Neutral C-N Coupling Reaction of Iminoquinones with Electron-Deficient Alkenes without External Oxidants: Access of Tertiary (E)-Enamines and Application to the Synthesis of Indoles and Quinolin-4-ones.

A novel and efficient reductive N-alkenylation of iminoquinones with electron-deficient olefins has been successfully developed by Pd(II)-catalyzed redox-neutral reactions, which provides a synthesis of tertiary (E)-enamines. We further demonstrate that the tertiary enamines can be converted to multifarious N-heterocyclic compounds, indoles, and quinolones in good yields.

Microfluidic electrochemistry for single-electron transfer redox-neutral reactions.

Electrochemistry offers opportunities to promote single-electron transfer (SET) redox-neutral chemistries similar to those recently discovered using visible-light photocatalysis but without the use of an expensive photocatalyst. Herein, we introduce a microfluidic redox-neutral electrochemistry (μRN-eChem) platform that has broad applicability to SET chemistry, including radical-radical cross-coupling, Minisci-type reactions, and nickel-catalyzed C(sp2)-O cross-coupling. The cathode and anode simultaneously generate the corresponding reactive intermediates, and selective transformation is facilitated by the rapid molecular diffusion across a microfluidic channel that outpaces the decomposition of the intermediates. μRN-eChem was shown to enable a two-step gram-scale electrosynthesis of a nematic liquid crystal compound, demonstrating its practicality.

Electrochemically Catalyzed Newman-Kwart Rearrangement: Mechanism, Structure-Reactivity Relationship, and Parallels to Photoredox Catalysis.

The facilitation of redox-neutral reactions by electrochemical injection of holes and electrons, also known as "electrochemical catalysis", is a little explored approach that has the potential to expand the scope of electrosynthesis immensely. To systematically improve existing protocols and to pave the way toward new developments, a better understanding of the underlying principles is crucial. In this context, we have studied the Newman-Kwart rearrangement of O-arylthiocarbamates to the corresponding S-aryl derivatives, the key step in the synthesis of thiophenols from the corresponding phenols. This transformation is a particularly useful example because the conventional method requires temperatures up to 300°C, whereas electrochemical catalysis facilitates the reaction at room temperature. A combined experimental-quantum chemical approach revealed several reaction channels and rendered an explanation for the relationship between the structure and reactivity. Furthermore, it is shown how rapid cyclic voltammetry measurements can serve as a tool to predict the feasibility for specific substrates. The study also revealed distinct parallels to photoredox-catalyzed reactions, in which back-electron transfer and chain propagation are competing pathways.

Modular Synthesis of Diarylalkanes by Nickel-Catalyzed 1,1-Diarylation of Unactivated Terminal Alkenes

A nickel-catalyzed 1,1-diarylation of electronically unbiased alkenes has been developed, providing straightforward access to diarylalkanes from readily available materials. Importantly, both the e...

Catalytic Sulfone Upgrading Reaction with Alcohols via Ru(II)

Sulfones and sulfonamides with an α-CH bond can be easily alkylated by aliphatic alcohols to add the carbon skeleton of the alcohol via a one-step, Ru(II)-catalyzed redox neutral reaction. The reac...

Chromium(III)-Catalyzed C(sp2)-H Alkynylation, Allylation, and Naphthalenation of Secondary Amides with Trimethylaluminum as Base.

Among base metals used for C-H activation reactions, chromium(III) is rather unexplored despite its natural abundance and low toxicity. We report herein chromium(III)-catalyzed C(sp2)-H functionalization of an ortho-position of aromatic and α,β-unsaturated secondary amides using readily available AlMe3 as a base and using bromoalkynes, allyl bromide, and 1,4-dihydro-1,4-epoxynaphthalene as electrophiles. This redox-neutral reaction taking place at 70-90 °C, requires as low as 1-2 mol % of CrCl3 or Cr(acac)3 as a catalyst without any added ligand, and tolerates functional groups such as aryl iodide, boronate, and thiophene groups. Stoichiometric and kinetics studies as well as kinetic isotope effects suggest that the catalytic cycle consists of a series of thermally stable but reactive intermediates bearing two molecules of the amide substrate on one chromium atom and also that one of these chromate(III) complexes takes part in the alkynylation, allylation, and naphthalenation reactions. The proposed mechanism accounts for the effective suppression of methyl group delivery from AlMe3 for ortho-C-H methylation.