Recent advances in heterogeneous catalytic hydrogenation and dehydrogenation of N-heterocycles

The selective hydrogenation of quinolines to 1,2,3,4-tetrahydroquinolines(py-THQ) and its derivatives has attracted a considerable amount of attention as they show great versatility in many pharmaceuticals, agrochemicals, and fine chemicals. Over the past few decades, great breakthroughs have been achieved in the controlled synthesis of efficient heterogeneous catalysts used for the selective hydrogenation of functionalized quinoline compounds, which allow one to correlate the structure-property relationships. In this review, we will summarize the recent significant progress achieved in this field covering the synthetic strategies, microstructural and chemical features, catalytic performance, and internal relationships. State-of-the-art noble metal-based single(Pd, Pt, Ru, Rh, Ir and Au) and bi/multi-metallic catalysts(RuCu, AuPd, and PdNi) are first introduced, followed by a summary of earth-abundant metal-based catalysts(Co, Fe, Ni, and Cu). Finally, the dehydrogenation of N-heterocycles is introduced to form a reversible hydrogenation/dehydrogenation system for H2 storage, which can be employed in a liquid organic hydrogen system. Furthermore, the reaction mechanism and future research direction in these areas are also discussed. This review will deepen our understanding of the catalytic transformation of N-heterocycles and provide guidance for researchers on the rational design of catalysts.

N-Heterocycles Extended π-Conjugation Enables Ultrahigh Capacity,Long-Lived,and Fast-Charging Organic Cathodes for Aqueous Zinc Batteries

The aqueous zinc-organic battery is a promising candidate for large-scale energy storage.However,the rational design of advanced organic cathodes with high capacity,long lifespan,and high rate capability remains a big challenge.Herein,we propose that extending theπ-conjugation by N-heterocycles can provide more active sites,lead to insolubility,and facilitate charge transfer,thus boosting the overall electrochemical performance of organic electrodes.Based on this concept,a novel organic compound,dipyrido[3ʹ,2ʹ:5,6;2″,3″:7,8]quinoxalino[2,3-i]dipyrido[3,2-a:2ʹ,3ʹ-c]phenazine-10,21-dione(DQDPD),has been rationally designed and evaluated as the cathode for aqueous zinc batteries.Excitingly,DQDPD shows a record high capacity(509 mAh g^(−1) at 0.1 A g^(−1),corresponding to a record-breaking energy density of 348 Wh kg^(−1)),excellent cycling stability(92%capacity retention after 7500 cycles at 10 A g^(−1)),and fast-charging capability(161 mAh g^(−1) at 20 A g^(−1)).Our work offers new ideas in the molecular engineering of organic electrodes for high-performance rechargeable batteries.

Recent Advances in Domino Synthesis of Fused Polycyclic N-Heterocycles Based on Intramolecular Alkyne Hydroamination under Copper Catalysis

Fused polycyclic N-heterocycles are very important scaffolds in biomedicinal chemistry and materials science.Intramolecular alkyne hydroamination is a powerful method for the construction of N-heterocycles.In the last two decades,copper-catalyzed domino reactions based on intramolecular alkyne hydroamination has emerged as a robust strategy for assembling various fused polycyclic N-heterocycles.Great progress has been achieved in this area.This short review covers the advances made in copper-catalyzed domino synthesis of fused polycyclic N-heterocycles based on the strategy from 2008 to 2023,and will hopefully serve as an inspiration towards the exploration of new copper-catalyzed versions of the transformation.The domino transformations are introduced and discussed from five aspects according to the different key processes involved in these reactions.

A sustainable thermochemical conversion of animal biomass to N-heterocycles

The production of high-valued organonitrogen chemicals,especially N-heterocycles,requires artificial N_(2)fixation accompanied by the consumption of fossil resources.To avoid the use of these energy-and resource-intensive processes,we develop a sustainable strategy to convert nitrogen-rich animal biomass into N-heterocycles through a thermochemical conversion process(TCP)under atmospheric pressure.A high percentage of N-heterocycles(87.51%)were obtained after the TCP of bovine skin due to the abundance of nitrogen-containing amino acids(e.g.,glycine,proline,and L-hydroxyproline).Animal biomass with more diverse amino acid composition(e.g.,muscles)yielded higher concentrations of amines/amides and nitriles after TCP.In addition,by introducing catalysts(KOH for pyrrole and Al_(2)O_(3)for cyclo-Gly-Pro)to TCP,the production quantities of pyrrole and cyclo-Gly-Pro increased to 30.79 mg g^(-1)and 38.88 mg g^(-1),respectively.This approach can be used to convert the significant animal biomass waste generated annually from animal culls into valued organonitrogen chemicals while circumventing NH3-dependent and petro-chemical-dependent synthesis routes.

Sustainable production of value-added N-heterocycles from biomass-derived carbohydrates via spontaneous self-engineering

Synthetic N-heterocyclic compounds,such as quinoxalines,have shown a crucial role in pharmaceutical as well as food and dye industries.However,the traditional synthesis toward N-heterocycles relies on multistep energy and costintensive non-sustainable processes.Here,we report a facile approach that allows one-step conversion of biomass-derived carbohydrates to valuable quinoxalines in the presence of aryl-1,2-diamines in water without any harmful metal catalysts/organic solvents via spontaneously engineering involved cascade reactions under hydrothermal conditions.Aryl-1,2-diamines are revealed as the key to propel this transformation through boosting carbohydrate fragmentation into small 1,2-dicarbonyl intermediates and subsequently trapping them for constituting stable quinoxaline scaffolds therefore avoiding a myriad of undesired side reactions.The tunability of product selectivity can be also achievable by adjusting the basicity of the reaction environment.Both batch and continuous-flow integrated processes were verified for production of quinoxalines in an exceptionally eco-benign manner(E-factor<1),showing superior sustainability and economic viability.

Using Methanol as a Formaldehyde Surrogate for Sustainable Synthesis of N-Heterocycles via Manganese-Catalyzed Dehydrogenative Cyclization

The development of an efficient and sustainable synthetic route for formaldehyde production from renewable feedstock,especially in combination with a subsequent transformation to straightforwardly construct valuable chemicals,is highly desirable.Herein,we report a novel manganese-catalyzed dehydrogenative cyclization of methanol as a formaldehyde surrogate with a variety of dinucleophiles for facile synthesis of N-heterocycles.The in situ generated formaldehyde via catalytic methanol dehydrogenation can be selectively trapped by diverse dinucleophiles to avoid several possible side reactions.The utilty of this transformation is further highlighted by its successful appliation to the synthesis of 13C-labeled N-heterocycles using 13CH_(3)OH as a readily accessible 13C-isotope reagent.

Acceptorless dehydrogenative amination of alkenes for the synthesis of N-heterocycles

Catalytic amination of alkenes is one of the most attractive reactions for the construction of complex heterocycles with nitrogen centers. Herein, we present that synergistic photoredox and cobaloxime catalysis allows for highly efficient and mild dehydrogenative reactions between various NH nucleophiles and di-, tri-, and tetrasubstituted alkenes in the absence of external oxidants, thus enabling access to an array of N-heterocycles. Notably, both Z-and E-alkene-containing N-heterocycles are accessible. Mechanistic studies indicated that the Z-cinnamyl derivatives could be generated by photocatalytic E to Z alkene isomerization through an energy transfer process. Moreover, we find that sluggish energy transfer could inhibit the E to Z alkene isomerization process, thus offering the cinnamyl derivatives with E-selectivity. Our results highlight the benefits of the reactions using dual photoredox and cobaloxime catalysis to lead to diverse N-heterocycles.

Catalytic Enantioselective Construction of Chiral Benzo-Fused N-Heterocycles through Friedel-Crafts-Type Electrophilic Chlorination

Chiral benzo-fused N-heterocycles are frequently found in natural and synthetic products.However,their synthesis usually suffers from different limitations such as difficulty in accessing appropriate starting materials and unsatisfactory stereoselectivities.In this work,an unprecedented chiral sulfide-catalyzed enantioselective Friedel-Crafts-type electrophilic chlorination is shown to construct various 3,4-functionalized tetrahydroquinolines with excellent enantio-and diastereoselectivities from readily available aniline derivatives.Interestingly,employing N-allyl 1-naphthanilides as substrates,divergent reactions via chlorocarbocyclization and dearomatization occurred to afford two chiral polycyclic benzo-fused N-heterocycles.The system that we developed extends the scope of asymmetric chlorination to general substrateswithout the need of a N-H group,and significantly promotes the synthesis of enantioenriched benzo-fused N-heterocycles.

Operationally Simple Enantioselective Silane Reduction of Ketones by the [Ir(OMe)(cod)]2/Azolium Catalytic System

An operationally simple protocol was designed for the enantioselective silane reduction (ESR) of ketones using air- and moisture-stable [Ir(OMe)(cod)]2 (cod = 1,5-cyclooctadiene) (3) as a metal catalyst precursor. This reaction was driven by chiral hydroxyamide-functionalized azolium salt 2. The catalytic ESR reaction could be performed under benchtop conditions at room temperature. Treatment of 2 with 3 in THF yielded the monodentate IrCl(NHC)(cod) (NHC = N-heterocyclic carbene) complex 4 in 93% yield, herein the anionic methoxy ligand of 3 serves as an internal base that deprotonates the azolium ring of 2. The well-defined Ir complex 4 catalyzed the ESR reaction of propiophenone (6) with (EtO)2MeSiH using the pre-mixing reaction procedure. Based on this success, the catalytic ESR reaction was designed and implemented using an in situ-generated NHC/Ir catalyst derived from 2 and 3. Thus, a wide variety of aryl ketones could be reduced to the corresponding optically active alcohols in moderate to excellent stereoselectivities at room temperature without temperature control. Since the high catalytic activity of 3 was observed, we next evaluated several other transition metal catalyst precursors for the catalytic ESR reaction under the influence of 2. This evaluation revealed that Ir(acac)(cod) (acac = acetylacetonate) (28) and [IrCl(cod)]2 (5) can be successfully used as metal catalyst precursors in the ESR reaction.

N-heterocyclic carbene as a promising metal-free electrocatalyst with high efficiency for nitrogen reduction to ammonia

Electrocatalytic nitrogen reduction reaction(NRR)at ambient conditions holds great promise for sustainably synthesizing ammonia(NH3),while developing highly-efficient,long-term stable,and inexpensive catalysts to activate the inert N≡N bond is a key scientific issue.In this work,on the basis of the concept"N-heterocyclic carbenes(NHCs)",we propose a carbon decorated graphitic-carbon nitride(C/g-C3N4)as novel metal-free NRR electrocatalyst by means of density functional theory(DFT)computations.Our results reveal that the introduced C atom in g-C3N4 surface can be regarded as NHCs and catalytic sites for activating N≡N bond,and are stabilized by the g-C3N4 substrate due to sterically disfavored dimerization.Especially,this NHCs-based heterogeneous catalysis can efficiently reduce the activated N2 molecule to NH3 with a low overpotential of 0.05 V via an enzymatic mechanism.Our work is the first report of NHCs-based electrocatalyst for N2 fixation,thus opening an alternative avenue for advancing sustainable NH3 production.

N-Heterocyclic carbene-catalyzed enantioselective(dynamic) kinetic resolutions and desymmetrizations

N-heterocyclic carbene-catalyzed enantioselective kinetic resolutions,dynamic kinetic resolutions,and desymmetrization reactions are systematically reviewed.The content is organized according to the activation modes involved in these transformations.Future advances within this highly active research field are discussed from our perspectives on the topic.

Chemoselective Transfer Hydrogenation of Nitroarenes with Ammonia Borane Catalyzed by Copper N-Heterocyclic Carbene Complexes

Herein,we present a method for the homogeneous hydrogenation of nitroarenes to produce anilines using low catalyst loading(1 mo%)of copper N-heterocyclic carbene complexes as the catalyst and ammonia borane as the source of hydrogen.A wide range of nitroarenes,featuring diverse functional groups,were selectively transformed into their corresponding primary aromatic amines with high yields.This process can be readily scaled up and exhibits compatibility with various sensitive functional groups,including halogen,trifluoromethyl,aminomethyl,alkenyl,cyano,ester,amide,and hydroxyl.Notably,this catalytic methodology finds application in the synthesis of essential drug compounds.Mechanistic investigations suggest that the in-situ-generated Cu-H species may serve as active intermediates,with reduction pathways involving species such as azobenzene,1,2-diphenylhydrazine,nitrosobenzene,and N-phenylhydroxylamine.

Recent advances in the synthesis and application of N-heterocyclic carbene-based molecular cages

N-Heterocyclic carbene(NHC)-based cages have emerged as a prominent and dynamic research area within the research field of chemistry. Leveraging the distinctive electronic and steric properties of NHC ligands, the design, synthesis, and application of these corresponding cages have garnered substantial scholarly interest. In recent years, we have witnessed the successful fabrication of diverse NHC-based cages through a range of synthetic methodologies, which hold significant potential for applications in molecular recognition and catalysis. In this review, we delve into the foundational synthetic strategies that underlie the creation of NHC-based cages, employing approaches encompassing metal–NHC chelation, coordination assembly,and covalent bonding. Additionally, we compile the diverse applications of these cages within catalytic processes and molecular recognition. Lastly, we shed light on the current limitations of synthesis and outline future trends in the development of NHCbased cages.

Enantioselective Alkylation of Aldehydes with Organoborons Enabled by Nickel/N-Heterocyclic Carbene Catalysis

Transition-metal-catalyzed asymmetric alkylation of aldehydes represents a straightforward strategy for the synthesis of chiral secondary alcohols.However,efficient methods using organoborons as coupling reagents are rare.Herein,we report a highly enantioselective nickel-catalyzed alkylation reaction of aldehydes,using readily available alkylborons as nucleophiles.A wide variety of chiral secondary alcohols were prepared from commercially available aldehydes with high yields.The key to the excellent enantioselectivity and chemoselectivity was the employment of a bulky C2-symmetric chiral NHC ligand.This protocol features excellent enantiocontrol,mild conditions,and good functional group compatibility.

Vanadium(V) Complexes Containing Unsymmetrical N-Heterocyclic Carbene Ligands: Highly Efficient Synthesis and Catalytic Behavior towards Ethylene/Propylene Copolymerization

The highly efficient method has been developed for the synthesis of NHC·VOCl_(3) containing symmetrical or unsymmetrical Nheterocyclic carbene(NHC) ligands by the transmetallation reaction of NHC·AgCl with VOCl_(3).The total isolated yield of VOCl_(3)[1,3-(2,4,6-Me_(3)C_(6)H_(2))_(2)(NCH=)_(2)C:](V4') reached 86% by transmetallation reaction,which is much higher than that(48%) by direct coordination method.This methodology has also been used to synthesize the novel vanadium complexes containing unsymmetrical NHC ligands of VOCl_(3)[PhCH_(2)NCH=CHNR)C:](V5',R=2,4,6-Me_(3)C_(6)H_(2);V6',R=2,4-Me_(2)-6-Ph-C_(6)H_(2);V7',R=2,6-^(i)Pr_(2)-C_(6)H_(3)) with high yield,which could not be obtained by direct coordination method.The catalytic activity and copolymerization ability would be improved by introducing unsymmetrical NHC ligands due to their less steric bulky effect.The vanadium complex V5' containing unsymmetrical NHC ligand exhibits higher catalytic activity(3.7×10^(5)g_(copolymer)·mol^(-1) of V·h^(-1)) than that of V4' containing symmetrical NHC ligand.Moreover,the higher propylene incorporation ratio(45.6 mol%) in the copolymers of ethylene with propylene could be obtained by using V5' than that(39.9%) by using V4'.The results would provide a highly efficient strategy for the synthesis of early transition metal complexes containing versitile NHC ligands,affording the catalyst with both high catalytic activity and copolymerization ability for the synthesis of high performance polyolefin elastomers.

Highly active binuclear Cu(Ⅱ) catalyst bearing an unsymmetrical bipyridine-pyrazole-amine ligand for the azide-alkyne cycloaddition reaction

Ligands containing NH groups often show special characteristics.In this paper,a well-defined dinuclear Cu（II） complex bearing an unsymmetrical bipyridine-pyrazole-amine ligand was synthesized by the condensation of N–H to release H2O.Using sodium L-ascorbate as a reductant,the binuclear complex showed excellent activity in 1,3-dipolar cycloaddition reactions between alkynes and azides to obtain 1,4-disubstituted triazoles in 95%–99% isolated yields.

Synthesis of thiopyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]furo[3,2-d]pyrimidines

Reactions of the 6-hydroxy-thiopyrano[3,4-c]pyridine-5-carbonitrile derivative 1 withα-halo-carbonyl compounds gave the ortho-substituted intermediates 2a-c which were converted into furo[2,3-b]thiopyrano[4,3-d]pyridines 3a-c by fusion of a furan moiety under basic conditions.Further cyclization of 3a-c led to a fusion of a pyrimidine ring,yielding the tetracyclic products 6,7 and 8.In addition,condensation of 6 with various aromatic aldehydes afforded the corresponding imines 9a,b.Mannich reaction of 7 gave products 10a,b.

Direct and Indirect Electro-Oxidative Intramolecular C–H Aminations

The ubiquity of N-heterocycles in marketed drugs makes the development of metal-free methodologies for constructing C–N bonds of considerable importance.As an environmentally friendly method,electro-oxidative intramolecular C–H amination has emerged as a powerful platform for synthesizing nitrogen-containing heterocycles under metal-and external oxidant-free conditions.In this minireview,the main achievements in this direction since 2020 are summarized,with an emphasis on the substrate scope and mechanistic aspects.The reactions are classifi ed into two categories:direct and indirect electro-oxidative intramolecular C–H aminations.

Two Amine-tethered Imidazolium NHC Ni(Ⅱ) Complexes: Synthesis, Structure and Catalytic Activity

Nickel（II） complexes Ni（L1）2 （1） and Ni（L2）2·CH3CN·H2O （2） （L1Cl = 2-（3-benzyl- 2,3-dihydroimidazlo-1-yl）-N-（pyridin-2-yl）acetamide, chloride salt, L2Cl = 2-（3-naphthalene-2- ylmethyl）-2,3-dihydro-imidazlo-1-yl）-N-phenylacetamide, chloride salt） with amide-functionalized imidazolium NHC ligand were synthesized and determined by single-crystal X-ray diffraction. Complex 1 crystallizes in the monoclinic system, space group P21/cwith a = 9.2561（19）, b = 15.138（3）, c = 20.750（4） A, β = 90.216（3）°, V = 2907.3（10） A^3 and Z = 4. Complex 2 crystallizes in the orthorhombic system, space group Pbca with a = 15.5469（16）, b = 15.3521（15）, c = 31.177（3） A, V = 7441.2（13） ？3 and Z = 8. They are stable in the air and formed via intermolecular weak interactions, including C-H···π contacts and C–H···O hydrogen bonds. Complex 1 was applied in Suzuki coupling reaction through the investigation of reaction conditions under the optimal choice conditions： 80 ℃, K3PO4, 3% mol catalysts, 6% mol PPh3 and toluene as solvent system could afford 96% yield in 5 h.

Dialkyl imidazolium acetate ionosilica as efficient and recyclable organocatalyst for cyanosilylation reactions of ketones

We report new heterogeneous organocatalyst based on silica hybrid supported N-heterocyclic carbene(NHC-)species.The organocatalyst is formed from an imidazolium iodide based ionosilica material,followed by iodide/acetate anion exchange.The imidazolium acetate generates the organocatalytic carbene via partial deprotonation of the imidazolium ring in situ.As monitored via EDX,solid state NMR and ion chromatography measurements,the iodide/acetate exchange involving the imidazolium ionosilica material took place only in small extent.Despite the fact that the exchanged material contains only a very small amount of acetate,we observed good catalytic activity and recyclability in cyanosilylation reactions of ketones with trimethylsilyl cyanide.The versatility of the catalyst was highlighted via reaction with several substrates,yielding the corresponding cyanohydrins in good yields.In recycling experiments,the material showed decreasing catalytic activity starting from the third reaction cycle,but high catalytic activity can be regenerated via another acetate treatment.Our work is important as it highlights the possibility to combine carbene chemistry and silica,which are antagonistic at a first glance.We show that imidazolium acetate based ionosilicas are therefore heterogeneous'proto-carbenes',and that there is no need to form strongly basic silica supported NHCs to obtain heterogeneous NHC-organocatalysts.This work therefore opens the route towards heterogeneous and re-usable NHC-organocatalysts from supported ionic liquid imidazolium acetates.