Reductive Coupling Reaction Research Articles

Reductive Coupling of N-Heteroarenes and 1,2-Dicarbonyls for Direct Access to γ-Amino Acids, Esters, and Ketones Using a Heterogeneous Single-Atom Iridium Catalyst.

Despite their significant importance, the challenges in direct and diverse synthesis of N-heterocyclic γ-amino acids/esters/ketones hamper exploration of their applications. Herein, by developing a multifunctional heterogeneous iridium single-atom catalyst composed of silica-confined iridium species and a boron-doped ZrO2 support (Ir-SAs@B-ZrO2/SiO2), we describe its utility in establishing a new reductive coupling reaction of N-heteroarenes and 1,2-dicarbonyls for selective and diverse construction of the as-described compounds in a straightforward manner. The striking features, including good substrate and functionality tolerance, high step and atom economy, exceptional catalyst reusability, and diversified product post-transformations, highlight the practicality of the developed chemistry. Mechanistic studies reveal that the synergy between the active Ir sites and acidic support favors a chemoselective reduction of the more inert N-heteroarenes and affords requisite enamine intermediates. In this work, the concept on precise transformation of reductive intermediates will open a door to further develop useful tandem reactions by rational catalyst design.

Nickel‐Catalyzed Reductive Protocol to Access Silacyclobutanes with Unprecedented Functional Group Tolerance

AbstractWhile significant progress has been made in the area of transition metal‐catalyzed ring‐opening and formal cycloaddition reactions of 1,1‐disubstituted silacyclobutanes (SCBs), synthesizing these SCBs—particularly those bearing additional functional groups—continues to present synthetic challenges. In this context, we present a novel Ni‐catalyzed reductive coupling reaction that combines 1‐chloro‐substituted silacyclobutanes with aryl or vinyl halides and pseudohalides, thereby obviating the need for organometallic reagents. This method facilitates the generation of 1,1‐disubstituted silacyclobutanes with a remarkable tolerance for various functional groups. This approach serves as a complementary and more step‐economical alternative to the commonly used yet moisture‐ and air‐sensitive nucleophilic substitution reactions involving Grignard or lithium reagents. Our initial mechanistic studies indicate that this reaction is initiated by oxidative cleavage of the Si−Cl bond in 1‐chlorosilacyclobutanes, which represents a distinct mechanism from the previously documented reductive coupling processes involving carbon electrophiles and chlorosilanes.

Nickel-Catalyzed Reductive Protocol to Access Silacyclobutanes with Unprecedented Functional Group Tolerance.

While significant progress has been made in the area of transition metal-catalyzed ring-opening and formal cycloaddition reactions of 1,1-disubstituted silacyclobutanes (SCBs), synthesizing these SCBs-particularly those bearing additional functional groups-continues to present synthetic challenges. In this context, we present a novel Ni-catalyzed reductive coupling reaction that combines 1-chloro-substituted silacyclobutanes with aryl or vinyl halides and pseudohalides, thereby obviating the need for organometallic reagents. This method facilitates the generation of 1,1-disubstituted silacyclobutanes with a remarkable tolerance for various functional groups. This approach serves as a complementary and more step-economical alternative to the commonly used yet moisture- and air-sensitive nucleophilic substitution reactions involving Grignard or lithium reagents. Our initial mechanistic studies indicate that this reaction is initiated by oxidative cleavage of the Si-Cl bond in 1-chlorosilacyclobutanes, which represents a distinct mechanism from the previously documented reductive coupling processes involving carbon electrophiles and chlorosilanes.

Modulating Hydrogen Adsorption by Unconventional p–d Orbital Hybridization over Porous High‐Entropy Alloy Metallene for Efficient Electrosynthesis of Nylon‐6 Precursor

AbstractRenewable electricity driven electrosynthesis of cyclohexanone oxime (C6H11NO) from cyclohexanone (C6H10O) and nitrogen oxide (NOx) is a promising alternative to traditional environment‐unfriendly industrial technologies for green synthesis of C6H11NO. Precisely controlling the reaction pathway of the C6H10O/NOx‐involved electrochemical reductive coupling reaction is crucial for selectively producing C6H11NO, which is yet still challenging. Herein, we report a porous high‐entropy alloy PdCuAgBiIn metallene (HEA‐PdCuAgBiInene) to boost the electrosynthesis of C6H11NO from C6H10O and nitrite, achieving a high Faradaic efficiency (47.6 %) and almost 100 % yield under ambient conditions. In situ Fourier transform infrared spectroscopy and theoretical calculations demonstrate that unconventional orbital hybridization between d‐block metals and p‐block metals could regulate the local electronic structure of active sites and induce electron localization of electron‐rich Pd sites, which tunes the active hydrogen supply, facilitates the generation and enrichment of key intermediates NH2OH* and C6H10O*, and efficiently promotes their C−N coupling to selectively produce C6H11NO.

Sequence-Controlled Electrochemical Immobilization of Catalyst-Photosensitizer Oligomers for Tuning Photoelectrochemical Behaviors.

Immobilizing catalysts and photosensitizers on an electrode surface is crucial in interfacial energy conversion. However, their combination for optimizing catalytic performance is an unpredictable challenge. Herein, we report that catalyst and photosensitizer monomers are selectively grafted one-by-one addition onto the electrode surface by interfacial electrosynthesis to achieve composition and sequence-controlled oligomer photoelectrocatalytic monolayers. This electrosynthesis relies on the oxidative coupling reaction of carbazole and the reductive coupling reaction of vinyl on the catalyst and photosensitizer monomers, and it initiates on self-assembled monolayers and propagates with alternating positive and negative potentials. Each addition and completion of the target monomer can be quantitatively identified and monitored by optical and electrical responses and their linear coefficients as a function of reaction steps. The resulting composition and sequence-controlled monolayers exhibit tuning electrocatalytic behaviors including water splitting and CO2 reduction, indicating an efficient way to optimize the electro- and photocatalytic functions and performance of molecular materials.

The Progress of Reductive Coupling Reaction by Iron Catalysis.

The transition metal catalyzed coupling reaction has revolutionized the strategies for forging the carbon-carbon bonds. In contrast to traditional cross-coupling methods using pre-prepared nucleophilic organometallic reagents, reductive coupling reactions for the C-C bonds formation provide some advantages. Because both coupling partners are reduced in the final products using a stoichiometric amount of a reductant, this approach not only avoids the need to use sensitive organometallic species, but also provides an orthogonal and complementary access to classical coupling reaction. Notably, the reductive coupling reactions feature readily available fragments, promote good step economy, exhibit high functional group tolerance and unique chemoselectivity, which have propelled their increasingly popular in the organic synthesis. In recent years, due to the low price, minimal toxicity, and environmentally benign character, iron-catalyzed carbon-carbon coupling reactions have garnered significant attention from the organic synthetic chemists and pharmacologists, especially the iron-catalyzed reductive coupling. This review aims to provide an insightful overview of recent advances in iron-catalyzed reductive coupling reactions, and to illustrate their possible reaction mechanisms.

Inside Cover Picture

The picture in the background is the old chemistry building of Soochow University, the symbols of S are: 1. for the research field of Prof. Wang Shunyi's group at Soochow University: Organic Sulfur Chemistry; 2. for Soochow University; 3. for Suzhou; 4. for Singapore. We would like to take this opportunity to celebrate the 110th anniversary of the founding of Chemistry and Chemical Engineering in Soochow University, as well as the 30th anniversary of the Suzhou‐Singapore Industrial Park. The cover image portrays the reductive coupling reaction of xanthate esters with sulfur‐containing and selenium‐containing compounds (thio(seleno)sulfonates and disulfides(selenides)) under the nickel‐catalyzed condition. It provides a mild and effective method for the synthesis of unsymmetric sulfides and selenides. More details are discussed in the article by Wang et al. on pages 2453—2458.image

Modulating Hydrogen Adsorption by Unconventional p-d Orbital Hybridization over Porous High-Entropy Alloy Metallene for Efficient Electrosynthesis of Nylon-6 Precursor.

Renewable electricity driven electrosynthesis of cyclohexanone oxime (C6H11NO) from cyclohexanone (C6H10O) and nitrogen oxide (NOx) is a promising alternative to traditional environment-unfriendly industrial technologies for green synthesis of C6H11NO. Precisely controlling the reaction pathway of the C6H10O/NOx-involved electrochemical reductive coupling reaction is crucial for selectively producing C6H11NO, which is yet still challenging. Herein, we report a porous high-entropy alloy PdCuAgBiIn metallene (HEA-PdCuAgBiInene) to boost the electrosynthesis of C6H11NO from C6H10O and nitrite, achieving a high Faradaic efficiency (47.6 %) and almost 100 % yield under ambient conditions. In situ Fourier transform infrared spectroscopy and theoretical calculations demonstrate that unconventional orbital hybridization between d-block metals and p-block metals could regulate the local electronic structure of active sites and induce electron localization of electron-rich Pd sites, which tunes the active hydrogen supply, facilitates the generation and enrichment of key intermediates NH2OH* and C6H10O*, and efficiently promotes their C-N coupling to selectively produce C6H11NO.

CO2-Promoted and Copper-Catalyzed Dehydroxylative Coupling of Benzylic Alcohols by the NaBH4/I2 System.

An efficient and CO2-promoted dehydroxylative coupling of benzylic alcohols catalyzed by ligand-free cuprous chloride has been achieved. The discovered catalytic reductive coupling reaction is a newly C-C bond-forming transformation of alcohols. Mechanistic insight is gained through control reactions.

Visible Light Catalyzed Reductive Cross‐Coupling of α‐CF3‐alkyl Bromide and Alkynyl Bromide†

Comprehensive SummaryTraditional reduction coupling reactions of two bromides typically rely on transition metal catalysis. Here, we introduce the development of a visible‐light catalytic direct reduction coupling reaction between α‐CF3‐alkyl bromides and alkynyl bromides to access valuable organic frameworks. Our research confirms the excellent compatibility of this reaction with various functional groups, which could be used to modify the substrate with biologically active molecular fragments. Mechanistic investigations, including control experiments, fluorescence quenching studies, and light‐switching experiments, have provided insights into the reaction mechanism. This study paves the way for the application of visible‐light catalysis in diverse synthetic transformations, offering a sustainable and efficient approach to organic synthesis.

Nickel(II)‐Catalyzed Reductive Coupling of Xanthate Esters with Sulfur‐Containing and Selenium‐Containing Compounds: Synthesis of Unsymmetric Sulfides and Selenides

Comprehensive SummaryUnsymmetric sulfides and selenides have great applications in the pharmaceutical field. Herein, we describe the reductive coupling reaction of xanthate esters with sulfur‐containing and selenium‐containing compounds (thio(seleno)sulfonates and disulfides(selenides)) under the nickel‐catalyzed condition. It provides a mild and effective method for the synthesis of unsymmetric sulfides and selenides which has the advantages of mild reaction conditions, high yields and a wide range of substrates.

Hydrogen‐Bond‐Mediated Formation of C−N or C=N Bond during Photocatalytic Reductive Coupling Reaction over CdS Nanosheets

AbstractReductive amination of carbonyl compounds and nitro compounds represents a straightforward way to attain imines or secondary amines, but it is difficult to control the product selectivity. Herein, we report the selective formation of C−N or C=N bond readily manipulated through a solvent‐induced hydrogen bond bridge, facilitating the swift photocatalytic reductive coupling process. The reductive‐coupling of nitro compounds with carbonyl compounds using formic acid and sodium formate as the hydrogen donors over CdS nanosheets selectively generates imines with C=N bonds in acetonitrile solvent; while taking methanol as solvent, the C=N bonds are readily hydrogenated to the C−N bonds via hydrogen‐bonding activation. Experimental and theoretical study reveals that the building of the hydrogen‐bond bridge between the hydroxyl groups in methanol and the N atoms of the C=N motifs in imines facilitates the transfer of hydrogen atoms from CdS surface to the N atoms in imines upon illumination, resulting in the rapid hydrogenation of the C=N bonds to give rise to the secondary amines with C−N bonds. Our method provides a simple way to control product selectivity by altering the solvents in photocatalytic organic transformations.

Hydrogen-Bond-Mediated Formation of C-N or C=N Bond during Photocatalytic Reductive Coupling Reaction over CdS Nanosheets.

Reductive amination of carbonyl compounds and nitro compounds represents a straightforward way to attain imines or secondary amines, but it is difficult to control the product selectivity. Herein, we report the selective formation of C-N or C=N bond readily manipulated through a solvent-induced hydrogen bond bridge, facilitating the swift photocatalytic reductive coupling process. The reductive-coupling of nitro compounds with carbonyl compounds using formic acid and sodium formate as the hydrogen donors over CdS nanosheets selectively generates imines with C=N bonds in acetonitrile solvent; while taking methanol as solvent, the C=N bonds are readily hydrogenated to the C-N bonds via hydrogen-bonding activation. Experimental and theoretical study reveals that the building of the hydrogen-bond bridge between the hydroxyl groups in methanol and the N atoms of the C=N motifs in imines facilitates the transfer of hydrogen atoms from CdS surface to the N atoms in imines upon illumination, resulting in the rapid hydrogenation of the C=N bonds to give rise to the secondary amines with C-N bonds. Our method provides a simple way to control product selectivity by altering the solvents in photocatalytic organic transformations.

Regioselective and Enantioselective Nickel-Catalyzed Intermolecular Reductive Coupling of Aliphatic Alkenes with Imines.

Unactivated aliphatic alkenes are particularly desirable as starting materials because they are readily accessible in large quantities, but the enantioselective intermolecular reductive coupling of unactivated alkenes with imines is challenging. In this paper, we report a method for nickel-catalyzed intermolecular reductive coupling reactions between aliphatic alkenes and imines to yield chiral amines with excellent enantioselectivities and good linear selectivities. The reaction conditions are compatible with a broad range of aliphatic alkenes, including those derived from bioactive molecules. The success of this method can be attributed to the use of newly developed monodentate chiral spiro phosphine ligands.

Carbonized cellulose microspheres loaded with Pd NPs as catalyst in p-nitrophenol reduction and Suzuki-Miyaura coupling reaction

Catalytic reduction of p-nitrophenol is usually carried out using transition metal nanoparticles such as gold, palladium, silver, and copper, especially palladium nanoparticles (Pd NPs), which are characterized by fast reaction rate, high turnover frequency, good selectivity, and high yield. However, the aggregation and precipitation of the metals lead to the decomposition of the catalyst, which results in a significant reduction of the catalytic activity. Therefore, the preparation of homogeneous stabilized palladium nanoparticles catalysts has been widely studied. Stabilized palladium nanoparticles mainly use synthetic polymers. Cellulose microspheres, as a natural polymer material with low-cost and porous fiber network structure, are excellent carriers for stabilizing metal nanoparticles. Cellulose microspheres impregnated with palladium metal nanoparticles were carbonized to have a larger specific surface area and highly dispersed palladium nanoparticles, which exhibited excellent catalytic activity in the catalytic reduction of p-nitrophenol. In this work, the cellulose carbon-based microspheres palladium (Pd@CCM) catalysts were designed and characterized by SEM, TEM, EDS, XRD, FTIR, XPS, TGA, BET, and so on. Furthermore, the catalytic performance of Pd@CCM catalysts was investigated via p-nitrophenol reduction, which showed high catalytic activity. This catalyst also exhibited excellent catalytic performance in the Suzuki-Miyaura coupling reaction. Linking aromatic monomer and benzene through Suzuki-Miyaura coupling was presented as an effective route to obtaining biaryls, and the synthesis method is low-cost and simple. In addition, Pd@CCM showed desirable recyclability while maintaining its catalytic activity even after five recycles. This work is highly suggestive of the design and application of the heterogeneous catalyst.

Catalyst Selection over an Electrochemical Reductive Coupling Reaction toward Direct Electrosynthesis of Oxime from NOx and Aldehyde.

Aqueous electrochemical coupling reactions, which enable the green synthesis of complex organic compounds, will be a crucial tool in synthetic chemistry. However, a lack of informed approaches for screening suitable catalysts is a major obstacle to its development. Here, we propose a pioneering electrochemical reductive coupling reaction toward direct electrosynthesis of oxime from NOx and aldehyde. Through integrating experimental and theoretical methods, we screen out the optimal catalyst, i.e., metal Fe catalyst, that facilitates the enrichment and C-N coupling of key reaction intermediates, all leading to high yields (e.g., ∼99% yield of benzaldoxime) for the direct electrosynthesis of oxime over Fe. With a divided flow reactor, we achieve a high benzaldoxime production of 22.8 g h-1 gcat-1 in ∼94% isolated yield. This work not only paves the way to the industrial mass production of oxime via electrosynthesis but also offers references for the catalyst selection of other electrochemical coupling reactions.

Nano-Cu Derived from a Copper Nitride Precatalyst for Reductive Coupling of Nitroaromatics to Azo Compounds.

The study of structural reconstruction is vital for the understanding of the real active sites in heterogeneous catalysis and guiding the improved catalyst design. Herein, we applied a copper nitride precatalyst in the nitroarene reductive coupling reaction and made a systematic investigation on the dynamic structural evolution behaviors and catalytic performance. This Cu3N precatalyst undergoes a rapid phase transition to nanostructured Cu with rich defective sites, which act as the actual catalytic sites for the coupling process. The nitride-derived defective Cu is very active and selective for azo formation, with 99.6% conversion of nitrobenzene and 97.1% selectivity to azobenzene obtained under mild reaction conditions. Density functional theory calculations suggest that the defective Cu sites play a role for the preferential adsorption of nitrosobenzene intermediates and significantly lowered the activation energy of the key coupling step. This work not only proposes a highly efficient noble-metal-free catalyst for nitroarenes coupling to valuable azo products but also may inspire more scientific interest in the study of the dynamic evolution of metal nitrides in different catalytic reactions.

Low-valent titanium(II) mediated intramolecular and regioselective alkyne/alkoxyallene reductive coupling reactions.

Low-valent titanium(II) complexes turned out to be suitable reagents in the promotion of alkyne/alkoxyallene coupling reactions in an intramolecular fashion. The conditions developed herein led to a broad range of highly functionalized cyclic adducts with excellent regioselectivities toward the central carbon of the alkoxyallene moiety. Good yields (up to 76%) were obtained over 19 examples. One-pot late functionalization by electrophile trapping was also possible and led to excellent diastereoselectivities (up to 95/5 d.r.).

Recent advances in photocatalytic and transition metal-catalyzed synthesis of disulfide compounds.

Disulfide bonds are essential in protein folding, cellular redox balance, materials science, and drug development. Despite existing synthetic methods, the efficient and selective synthesis of unsymmetrical disulfides remains challenging. This review highlights innovative approaches in visible light photocatalysis, including decarboxylation, deoxydisulfidation of alcohols, and direct C-H disulfidation, showcasing broad substrate applicability and functional group tolerance under mild conditions. Additionally, it explores transition metal-catalyzed systems with copper, nickel, palladium, chromium, Iridium, Rhodium molybdenum, and scandium, offering effective strategies for unsymmetrical disulfide bond formation and late-stage functionalization of complex molecules through reductive coupling, selective oxidation, and novel insertion reactions.

Light-driven asymmetric coupling of aromatic aldehydes and aryl iodides using a simple amine reductant

In light of overcoming the sustainability challenge in reduction processes by using a ‘greener’ yet less reactive reductant, a cobalt-catalyzed asymmetric reductive coupling reaction of aromatic aldehydes and aryl iodides has been developed with i-Pr2NEt as the reductant.