2022

Abstract:

The use of spectroscopy to characterize electrocatalytic processes is vital to the understanding and continuing the development of new catalysts for clean energy transformations. Electron paramagnetic resonance spectroscopy (EPR), which allows for the study of unpaired electron spins, shows great fundamental promise for the study of electrocatalysts, but was previously hindered by design limitations. Recently, several groups have demonstrated that these limitations can be overcome, providing valuable understandings of electrocatalyst function that other techniques are less suitable for. In this review, we summarize these findings across a range of experimental approaches and systems and describe the importance of EPR to each of these studies. By providing outlines for how these studies were able to overcome experimental design challenges, we hope to provide insight into potentially interested users.

Abstract:

Aryl borates lie at the heart of carbon–carbon bond couplings, and they are widely applied to the synthesis of functional materials, pharmaceutical compounds, and natural products. Currently, synthetic methods for aryl borates are mostly limited to metal-catalyzed routes, and nonmetallic strategies remain comparatively underdeveloped. Herein, we report a mild, scalable, visible-light-induced cross-coupling between aryl dibenzothiophenium triflate salts and bis(catecholato)-diboron for the construction of C–B bonds in the absence of base, transition metal–ligand complex, or photoredox catalyst. Mechanistic studies reveal that this transformation is achieved through an electron donor–acceptor (EDA) complex activation in the absence of a catalyst. The mild reaction conditions allow the preparation of aromatic borates in good yields with excellent functional group tolerance. This photochemical protocol was also successfully applied to the late-stage modification of natural products and the synthesis of a drug intermediate, greatly demonstrating broadened utility.

Abstract:

Mo-based catalysts constitute a significant portion of active non-noble H2 evolution reaction (HER) catalysts, but the role of Mo in conferring this activity remains debated. In this study, we utilize electrochemical, physical, functional, and computational approaches on a range of Mo-based catalysts to derive a unified explanation for Mo HER catalyst function. Across all catalysts studied, the formation of Mo3+ at cathodic potentials close to the thermodynamic HER onset drives activity, and activity between catalysts is therefore heavily determined by the ease of reduction from Mo4+ to Mo3+. As such, surface oxidation is detrimental to HER activity as it makes Mo3+ formation less facile. This theory provides a cohesive explanation for the origin of activity in Mo-based HER catalysts, emphasizing the specific role of Mo atoms in forming hydrides and carrying out the HER from Mo3+, with implications for future Mo catalyst design.

Abstract:

Divergent synthesis of medium-sized rings with controllable ring sizes represents a longstanding challenge in organic synthesis. Herein, we developed a transition-metal-catalyzed switchable divergent cycloaddition of para-quinone methides and vinylethylene carbonates by controlling the steric hindrance of substituent. Different from reported alkoxide-triggered annulations, this process undergoes a regiodivergent allylation of para-quinone methides followed by 1,6-addition reaction, providing a new route to selectively synthesize seven- to ten-membered nitrogen-containing heterocycles in high yields with excellent regioselectivities. This protocol features a broad substrate scope, wide functional group tolerance as well as operational simplicity. The reaction mechanism was investigated by conducting a series of control experiments as well as DFT calculations and the origins of the regioselectivities of the cycloaddition process were rationalized.

Abstract:

Surface organometallic chemistry (SOMC) has mainly been devoted to the reaction of organometallics with surfaces comprising highly divided and dehydroxylated oxides. The field has been extended to SOMC on metal nanoparticles. However, to the best of our knowledge, SOMC has not been extended to hierarchical fibrous zeolites, although zeolitic materials are a particular class of oxides. Zeolite catalysis is important in hydrocarbon industrial chemistry. However, having an optimum balance between the activity and selectivity of the zeolitic catalysts remains a major challenge in the field. The main difficultly is the plethora of surface sites, only some of which are catalytically active. Given that the acido–basic properties and porosity of zeolites are especially important to the refining and petrochemical industries, we decided to explore this rather unexplored area. Here, three novel well-defined single-site materials [(Np)3M@ZSM-5, M = Ti, Zr, and Hf] supported on a hierarchical mesoporous H-ZSM-5 material (1) are reported. They are prepared using the concepts and tools of SOMC. They are further converted to their corresponding metal hydride [(H)nM@ZSM-5, M = Ti, Zr, and Hf, (n = 1–2)] materials (5–7) through controlled hydrogenolysis of [(≡Si–O−)M(Np)3, M = Ti, Zr, and Hf] materials (2–4) under H2 (1 atm) at 150 °C for 16 h. All these surface catalysts are characterized by various spectroscopic techniques including Fourier transform infrared spectroscopy, elemental analysis, solid-state NMR spectroscopy, powder X-ray diffraction, Brunauer–Emmett–Teller surface area measurements, and scanning electron microscopy and high-resolution transmission electron microscopy analyses and are supported by density functional theory calculations. The catalytic activity of these well-defined single-site novel materials will be tested for the catalytic applications in petrochemistry for refinery processes such as hydrocracking of distillates from crude oil or intermediate refinery process streams to useful petroleum value-added products for the society.

Abstract:

The advent and development of photoredox/nickel synergistic catalysis have enabled the use of various alkyl radical precursors in the cross-coupling arylation, yet none has addressed the challenge of regiodivergent synthesis. Herein, we disclose a visible light nickel-catalyzed protocol for the deaminative cross-coupling of redox-active imines with various electrophiles that allow for the rapid construction of C(sp3) enriched arene architectures in a regiodivergent manner. Key to the success of this protocol is the combination of a readily available organic photocatalyst and a Lewis acid additive. As an additional approach to alkylarenes, we also showcase that the nature of electrophiles dictates the regiochemical outcome.

Abstract:

A decarboxylative cyanation of amino acids under paired electrochemical reaction conditions has been developed. 4-CN-pyridine was found to be a new and effective cyanation reagent under catalyst-free conditions. Mechanistic studies support a nucleophilic reaction pathway, and the cyanation protocol can be applied to diverse substrates including N,N-dialkyl aniline and indole derivatives.

Abstract:

Herein, we report a reductive cross-coupling reaction of α-oxy halides, simply generated from aldehydes, with a series of C(sp2)- and C(sp)-electrophiles. A wide range of aryl and heteroatom aryl halides, vinyl bromides, alkynyl bromides, and acyl chlorides react with unhindered and hindered aldehyde-derived α-oxy halides by providing protected alcohols as well as α-hydroxy ketones. Noteworthy, the reductive couplings are achieved not only through thermal catalysis with the use of metal reductants but also by photocatalysis, electrochemistry, and mechanochemistry. The unrestricted interchange of the four strategies indicates their underlying mechanistic similarities. The generation of NiI intermediate is proposed to be the key point for ketyl radical formation via a single-electron transfer (SET) event, which was rationalized by an array of control experiments and density functional theory (DFT) calculations.

Abstract:

The aza-ortho-quinone methide (aza-o-QM) chemistry has overwhelmingly progressed in the past few decades. This review aims to integrate various transition metal-catalyzed and organocatalytic strategies in taming aza-o-QM intermediates, including the aza-ortho-vinylidene quinone methide (aza-o-VQM), aza-ortho-alkynyl quinone methide (aza-o-AQM), aza-para-quinone methide (aza-p-QM), and indole-based aza-o-QM analog. These transient species are often utilized for the direct and enantioselective synthesis of complex (hetero)polycyclic or fused-ring molecular scaffolds such as tetrahydroquinoline and indoline, among others, which are abundant in many natural products, bioactive compounds, and pharmaceuticals.

Abstract:

The nickel-catalyzed three-component reductive carbonylation of alkyl halides, aryl halides, and ethyl chloroformate is described. Ethyl chloroformate is utilized as a safe and readily available source of CO (carbon monoxide) in this multi-component protocol, providing an efficient and practical alternative for the synthesis of aryl-alkyl ketones. The reaction exhibits a wide substrate scope and good functional group compatibility. Experimental and DFT mechanistic studies highlight the complexity of the cross-electrophile coupling and provide insight into the sequence of the three consecutive oxidative additions of aryl halide, chloroformate, and alkyl halide.

Abstract:

Activation of aryl chlorides in cross-coupling reactions is a long-standing challenge in organic synthesis that is of great interest to industry. Ultrasmall (<3 nm), atomically precise nanoclusters (NCs) are considered one of the most promising catalysts due to their high surface area and unsaturated active sites. Herein, we introduce a copper nanocluster-based catalyst, [Cu61(StBu)26S6Cl6H14] (Cu61NC) that enables C–N bond-forming reactions of aryl chlorides under visible-light irradiation at room temperature. A range of N-heterocyclic nucleophiles and electronically and sterically diverse aryl/hetero chlorides react in this new Cu61NC-catalyzed process to afford the C–N coupling products in good yields. Mechanistic studies indicate that a single-electron-transfer (SET) process between the photoexcited Cu61NC complex and aryl halide enables the C–N-arylation reaction.

12. Nickel catalyzed multicomponent stereodivergent synthesis of olefins via aryl alkylation of alkynes enabled by electrochemistry, photocatalysis and photo-electrochemistry

Chen Zhu, Huifeng Yue, Magnus Rueping

Nat Commun 2022, 13, 3240

Abstract:

Trisubstituted alkenes are important organic synthons and have broad applications in the synthesis of many pharmaceuticals and materials. The stereoselective synthesis of such compounds has long been a research focus for organic researchers. Herein, we report a three-component, reductive cascade, cross-coupling reaction for the arylalkylation of alkynes. A wide range of trisubstituted alkenes are obtained in good to high yields with excellent chemo- and stereoselectivity by switching between electrochemistry and photocatalysis. The E isomer of the product is obtained exclusively when the reaction is conducted with electricity and nickel, while the Z isomer is generated with high stereoselectivity when photo- and nickel dual catalysts are used. Moreover, photo-assisted electrochemically enabled nickel catalyzed protocol is demonstrated to selectively deliver Z-trisubstituted alkenes without the addition of photocatalysts.

11. Air-loaded Gas Vesicle Nanoparticles Promote Cell Growth in Three-dimensional Bioprinted Tissue Constructs

Salwa Alshehri, Ram Karan, Sarah Ghalayini, Kowther Kahin, Zainab Khan, Dominik Renn, Sam Mathew, Magnus Rueping, Charlotte AE Hauser

Int J Bioprint, 2022, 8, 489

Abstract:

Three-dimensional (3D) bioprinting has emerged as a promising method for the engineering of tissues and organs. Still, it faces challenges in its widespread use due to issues with the development of bioink materials and the nutrient diffusion barrier inherent to these scaffold materials. Herein, we introduce a method to promote oxygen diffusion throughout the printed constructs using genetically encoded gas vesicles derived from haloarchaea. These hollow nanostructures are composed of a protein shell that allows gases to permeate freely while excluding the water flow. After printing cells with gas vesicles of various concentrations, the cells were observed to have increased activity and proliferation. These results suggest that air-filled gas vesicles can help overcome the diffusion barrier throughout the 3D bioprinted constructs by increasing oxygen availability to cells within the center of the construct. The biodegradable nature of the gas vesicle proteins combined with our promising results encourage their potential use as oxygen-promoting materials in biological samples.

10. Mechanistic insights into photochemical nickel-catalyzed cross-couplings enabled by energy transfer

Rajesh Kancherla, Krishnamoorthy Muralirajan, Bholanath Maity, Safakath Karuthedath, Gadde Sathish Kumar, Frédéric Laquai, Luigi Cavallo, Magnus Rueping

Nat Commun 2022, 13, 2737

Abstract:

Various methods that use a photocatalyst for electron transfer between an organic substrate and a transition metal catalyst have been established. While triplet sensitization of organic substrates via energy transfer from photocatalysts has been demonstrated, the sensitization of transition metal catalysts is still in its infancy. Here, we describe a protocol for the selective alkylation of α-oxy C(sp3)–H bonds by the direct coupling of ethers and toluene with alkyl bromides by excited-state nickel catalysis. DFT and TD-DFT calculations point to a mechanism involving a Dexter triplet-triplet EnT from the *Ir(III) photosensitizer to the organometallic Ni(II) catalyst. The formation of the Ni(II) triplet state was further supported by nanosecond transient absorption spectroscopy, and the energy transfer rate constant was determined by time-resolved photoluminescence studies. The crucial C–H functionalization step via hydrogen atom transfer (HAT) is mediated by the bromine radical generated by the homolytic cleavage of the Ni–Br bond of the excited-state Ni(II) catalyst. The scope of the reaction was explored using a variety of alkyl halides, including secondary halides that reacted efficiently to enable secondary–secondary carbon bond formation. Furthermore, the study highlights that for photochemical/metal-catalyzed reactions next to SET pathways also energy transfer processes need to be considered. Our combined experimental, computational studies, and detailed spectroscopic measurements provide an insight into the photophysics and mechanism of photosensitised nickel excited state catalysis and will guide the further development of this exciting field of catalysis

9. Mo3+ hydride as the common origin of H2 evolution and selective NADH regeneration in molybdenum sulfide electrocatalysts

Jeremy A Bau, Abdul-Hamid Emwas, Pavlo Nikolaienko, Areej A Aljarb, Vincent Tung, Magnus Rueping

Nat Catal 2022, 5, 397- 404. https://doi.org/10.1038/s41929-022-00781-8

Abstract:

Hydride transfers are key to a number of economically and environmentally important reactions, including H2 evolution and NADH regeneration. The electrochemical generation of hydrides can therefore drive the electrification of chemical reactions to improve their sustainability for a green economy. Catalysts containing molybdenum have recently been recognized as among the most promising non-precious catalysts for H2 evolution, but the mechanism by which molybdenum confers this activity remains debated. Here we show the presence of trapped Mo3+ hydride in amorphous molybdenum sulfide (a-MoSx) during the hydrogen evolution reaction and extend its catalytic role to the selective hydrogenation of the biologically important energy carrier NAD to its active 1,4-NADH form. Furthermore, this reactivity applies to other HER-active molybdenum sulfides. Our results demonstrate a direct role for molybdenum in heterogeneous H2 evolution. This mechanistic finding also reveals that molybdenum sulfides have potential as economic electrocatalysts for NADH regeneration in biocatalysis.

Abstract:

The addition of a B–H bond to an unsaturated bond (polarized or unpolarized) is a powerful and atom-economic tool for the synthesis of organoboranes. In recent years, s-block organometallics have appeared as alternative catalysts to transition-metal complexes, which traditionally catalyze the hydroboration of unsaturated bonds. Because of the recent and rapid development in the field of hydroboration of unsaturated bonds catalyzed by alkali (Li, Na, K) and alkaline earth (Mg, Ca, Sr, Ba) metals, we provide a detailed and updated comprehensive review that covers the synthesis, reactivity, and application of s-block metal catalysts in the hydroboration of polarized as well as unsaturated carbon–carbon bonds. Moreover, we describe the main reaction mechanisms, providing valuable insight into the reactivity of the s-block metal catalysts. Finally, we compare these s-block metal complexes with other redox-neutral catalytic systems based on p-block metals including aluminum complexes and f-block metal complexes of lanthanides and early actinides. In this review, we aim to provide a comprehensive, authoritative, and critical assessment of the state of the art within this highly interesting research area.

Abstract:

In the biosynthesis sterols an enzyme-catalyzed demethylation is achieved via a stepwise oxidative transformation of alcohols to olefins. The overall demethylation proceeds through two sequential monooxygenation reactions and a subsequent dehydroformylative saturation. To mimic the desaturation processes observed in nature, we have successfully integrated photoredox proton-coupled electron transfer (PCET) and cobaloxime chemistry for the acceptorless dehydrogenation of alcohols. The state-of-the-art remote and precise desaturation of ketones proceeds efficiently through the activation of cyclic alcohols using bond-dissociation free energy (BDFE) as thermodynamic driving force. The resulting transient alkoxyl radical allows C-C bond scission to generate the carbon-centered radical remote to the carbonyl moiety. This key intermediate is subsequently combined with cobaloxime photochemistry to furnish the alkene. Moreover, the mild protocol can be extended to desaturation of linear alcohols as well as aromatic hydrocarbons. Application to bioactive molecules and natural product derivatives is also presented.

6. Brønsted acid catalyzed enantioselective addition of hydrazones to 3-indolylmethanols

Steffen Mader, Modhu Sudan Maji, Iuliana Atodiresei, Magnus Rueping

Org. Chem. Front., 2022, 9, 4466-4471

Abstract:

The organocatalytic asymmetric addition of hydrazones to indole derivatives in the presence of chiral Brønsted acids is reported. A large variety of substrates are tolerated and the products are obtained in good yields and with excellent enantioselectivities. This metal-free reaction provides a convenient route to enantiopure β-substituted tryptophan derivatives in a concise fashion. We have developed a general metal-free highly enantioselective method which allows the synthesis of artificial tryptophan derivatives. The chiral phosphoric acid 3h enables the addition of donor-substituted hydrazones to 3-indolylmethanols in excellent yields and with excellent enantioselectivity values.

5. Visible-light, excited-state palladium-catalysed reductive alkylation of imines: scope and mechanism

Rajesh Kancherla, Krishnamoorthy Muralirajan, Magnus Rueping

Chem. Sci., 2022, 13, 8583-8589

Abstract:

Palladium catalysis induced by visible-light irradiation is a promising tool for promoting unusual chemical transformations. We describe the development of excited-state palladium-catalyzed reductive alkylation of imines with alkyl bromides. The new methodology shows broad functional group tolerance and can additionally be applied in the direct three-component reaction of aldehydes, anilines, and alkyl bromides to give the alkyl amines under mild reaction conditions. Time-resolved photo-luminescence experiments allowed the determination of the excited-state reaction kinetics and indicate that the reaction is proceeding via the inner-sphere electron transfer mechanism.

4. Advances in allylic and benzylic C–H bond functionalization enabled by metallaphotoredox catalysis

Huifeng Yue, Chen Zhu, Long Huang, Abhishek Dewanji, Magnus Rueping

Chem. Commun., 2022, 58, 171-184

Abstract:

Metallaphoto-catalysis has been established as a robust platform for efficient construction of a range of chemical bonds. Moreover, transformation of native functionalities such as C(sp3)–H bonds to produce functional molecules represents one of the most attractive strategies in organic synthesis. Merging two powerful methodologies, metallaphoto-catalyzed benzylic and allylic C(sp3)–H bond functionalizations provide a series of general and mild approaches for diversification of alkylbenzenes and alkenes. We have highlighted the recent progress seen with metallaphoto-catalyzed functionalization of benzylic and allylic C(sp3)–H bonds. The newly developed approaches have been classified according to the type of transformation, including arylation, acylation, alkylation, carboxylation, alkynylation, sulfonylation and azidation. The illustrated methodologies enable the application of abundant hydrocarbons such as ethylbenzenes and alkenes as coupling partners in transition-metal catalyzed reactions. The transformations of more native functionalities to high-value compounds and the advantages of step and atom economy made these protocols appealing. The mild benzylic and allylic radical generating pathways involving HAT or SET allow the reactions to occur under very mild conditions, proceed with good chemo- and regioselectivity and illustrate good functional group compatibility. In some cases, an excess of C–H substrate is required for the transformations, possibly to boost the rate of bimolecular HAT and compete with radical annihilations. Future studies should focus on a few key challenges. First, the mechanism should be investigated in more detail since different research groups have described slightly different mechanisms for similar transformations. Second, compared to C–C bond formation, C-heteroatom bond formation via benzylic and allylic C(sp3)–H activation remains undeveloped and deserves more attention. Additionally, from the standpoint of practicability, more heterogeneous catalytic modes employing reusable photocatalysts should be developed. Moreover, considering the exclusive advantages of electrocatalysis, a combination of electro- or photoelectrocatalysis with C–H bond activation would be attractive. In addition, more effort should be dedicated to developing other efficient chiral ligands for asymmetric C–H bond functionalization and using benzylic and allylic radicals in more multicomponent reactions.

3. Metal-free C–Se cross-coupling enabled by photoinduced inter-molecular charge transfer

Chen Zhu, Serik Zhumagazy, Huifeng Yue, Magnus Rueping

Chem. Commun., 2022, 58, 96-99

Abstract:

Metal-free C–Se cross-couplings via the formation of electron-donor–acceptor (EDA) complexes have been developed. The visible-light induced reactions can be applied for the synthesis of a series of unsymmetrical diaryl selenides employing aryl bromides, aryl iodides as well as aryl chlorides under mild reaction conditions. The scale-up was readily achieved. UV-Vis spectroscopy measurements provide insight into the reaction mechanism. A mild and efficient visible-light method for C–Se bond formation has been developed. The new protocol proceeds via a photoinduced intermolecular charge transfer between the EDA complex of aryl halide, selenol, and base. The practicality of this metal-free selenylation methodology is illustrated by the broad substrate scope, the late-stage functionalization of more complex molecules, and the successful gram-scale reaction. UV-Vis absorption spectroscopy measurements reveal that EDA complexes are involved in this process. The catalytic protocol is a general, metal-free, and low-cost alternative to transition-metal-catalyzed C–Se bond cross-coupling reactions and, thus, should find use in applications in which metal impurities are detrimental.

Abstract:

Herein we report the deoxygenated fluorination of readily available carboxylic acids. A series of acyl fluorides have been synthesized using shelf-stable N-trifluoromethylthiophthalimide as a fluorinated reagent for the first time. Scale-up reactions and sequential cross-couplings were performed successfully to demonstrate the practicability of this fluorination protocol. We have developed an efficient deoxygenated fluorination of readily available carboxylic acids. In contrast to previous reports wherein bench-stable N-trifluoromethylthio-phthalimide was always used as a trifluoromethylthiolation reagent, this newly developed protocol employed it as a fluorinated reagent for the first time. A series of aryl and vinyl carboxylic acid could be converted to acyl fluorides with good to high efficiency. Gram-scale reaction and sequential synthesis, including deoxygenated fluorination/decarbonyl-ative alkylation/C–O bond arylation, were realized in good yield. This protocol provides a good alternative for the fluorination of carboxylic acids.

1. Nickel-catalyzed reductive cross-couplings: new opportunities for carbon–carbon bond formations through photochemistry and electrochemistry

Liang Yi, Tengfei Ji, Kun-Quan Chen, Xiang-Yu Chen, Magnus Rueping

CCS Chem. 2022, 4, 9-30

Abstract:

Metal-catalyzed cross-electrophile couplings have become a valuable tool for carbon–carbon bond formation. This minireview provides a comprehensive overview of the recent developments in the topical field of cross-electrophile couplings, provides explanations of the current state-of-the-art, and highlights new opportunities arising in the emerging fields of photoredox catalysis and electrochemistry. Nickel-catalyzed reductive cross-couplings provide an efficient and economical way for the construction of C–C bonds using abundant and stable electrophiles as coupling partners. However, the requirement of a stoichiometric reductant can complicate scale-up and generate excess stoichiometric metal waste. Taking advantage of the development of synthetic techniques especially electro- and photochemistry, cross-electrophile coupling has become more environmentally friendly for selective C–C bond formation without using metal powders. The newly developed environmentally friendly techniques, which enable chemists to create new activation modes, will be one of the future directions in this area. An important step in reductive cross-coupling is to reduce the high-valent nickel intermediate and regenerate the active nickel catalyst. On the basis of the types of reducing agents, three reaction protocols have been used in cross-electrophile couplings: (1) Traditional strategy-stoichiometric metallic reducing agents are employed for the reduction of Ni(II) and Ni(I) species; (2) Photochemistry in which a photoredox catalyst and an organic reductant are used for generation of alkyl radicals and regeneration of the nickel catalyst; (3) Electrochemistry in which direct cathodic reduction is used for the reduction of Ni(II) and Ni(I) species and the generation of organic radicals. The development of photo- and electroreductive cross-coupling is still in its infancy. In the case of nickel-catalyzed reductive cross-couplings, future progress will result from efforts to develop C(sp2)–C(sp2) and C(sp3)–C(sp3) bond formations and more general enantioselective approaches. Importantly, a better understanding of the reaction mechanism, in particular with respect to the photo- and electrochemical reactions, is required to design more stable, efficient, and scalable catalyst systems for these valuable cross-electrophile couplings.