Hydrodeoxygenation of 2,5-dimethyltetrahydrofuran over bifunctional Pt–Cs2.5H0.5PW12O40 catalyst in the gas phase: enhancing effect of gold

2,5-Dimethyltetrahydrofuran (DMTHF) is deoxygenated to n-hexane with >99% selectivity at mild conditions (90 °C, 1 bar H₂ pressure, fixed-bed reactor) in the presence of the bifunctional metal-acid catalyst Pt–CsPW comprising Pt and Cs_2.5H_0.5PW₁₂O₄₀ (CsPW), an acidic Cs salt of Keggin-type heteropoly acid H₃PW₁₂O₄₀. Addition of gold to the Pt–CsPW catalyst increases the turnover rate at Pt sites more than twofold, whereas the Au alone without Pt is not active. The enhancement of catalyst activity is attributed to PtAu alloying, which is supported by STEM-EDX and XRD analysis.

Addition of gold to the Pt–CsPW catalyst has an enhancing effect on the HDO of DMTHF, with a twofold increase of turnover rate at Pt sites.

Biomass-derived furanic compounds are of interest as a renewable feedstock, which can be processed into a range of value-added chemicals and green fuels via catalytic hydroconversion.^1–8 Hydrodeoxygenation (HDO) of furanic compounds using bifunctional metal–acid catalysis has been demonstrated to be an effective strategy to produce green fuels under mild conditions^3,4,6,8–12 and references therein. The HDO over bifunctional metal-acid catalysts is much more efficient compared to the reaction over monofunctional metal catalysts.^11,12 Previously, we have reported HDO of a wide range of oxygenates in the gas phase to produce alkanes in the presence of bifunctional catalysts comprising Pt, Ru, Ni and Cu as metal components and Keggin-type heteropoly acids, with their activity decreasing in the order Pt > Ru > Ni > Cu.^13,14 Pt–CsPW comprising Pt and strongly acidic heteropoly salt Cs_2.5H_0.5PW₁₂O₄₀ (CsPW) has been reported to be a highly efficient catalyst for the HDO of 2,5-dimethylfuran (DMF) and 2,5-dimethyltetrahydrofuran (DMTHF) to produce n-hexane with 100% yield at 90–120 °C and ambient pressure.^11,12 The HDO of DMTHF over Pt–CsPW occurs through a sequence of hydrogenolysis, dehydration and hydrogenation steps catalysed by Pt and proton sites of the bifunctional catalyst (Scheme 1). These include the ring opening of DMTHF to form 2-hexanol on Pt sites followed by its dehydration on proton sites of CsPW to hexene, which is finally hydrogenated to n-hexane on Pt sites.¹² It is the facile dehydration of the secondary alcohol intermediate that drives the HDO process forward.^11,12 The rate-limiting step is either the ring hydrogenolysis or 2-hexanol dehydration depending on the ratio of accessible surface metal and acid sites Pt/H⁺.¹² Other platinum group metals such as Pd, Ru and Rh, that have high selectivity to ring hydrogenation rather than ring hydrogenolysis,^2,7 have low activities in HDO of DMF and DMTHF.¹¹Open in a separate windowScheme 1Reaction pathway for hydrodeoxygenation of DMTHF over Pt–CsPW.Bimetallic PtAu and PdAu catalysts have been reported to have an enhanced performance in comparison to monometallic Pt and Pd catalysts,^15–31 for example, in hydrogenation,^16,21,29 hydrodesulphurisation,^27,28 oxidation,^22,24 isomerisation^15,19,30,31 and other reactions.^{17,18,20,25,26} The enhancement of catalyst performance by addition of gold can be attributed to geometric (ensemble) and electronic (ligand) effects of the constituent elements in PtAu and PdAu bimetallic species.^25,26Here we looked at the effect of Au on the performance of Pt–CsPW catalysts in the HDO of DMTHF in the gas phase (see the ESI for experimental details^†). The CsPW heteropoly salt is a well-known solid acid catalyst; it possesses strong proton sites, large surface area and high thermal stability (∼500 °C decomposition temperature).^9,32–34 Supported bimetallic catalysts PtAu/SiO₂ and PtAu/CsPW were prepared by co-impregnation of H₂PtCl₆ and HAuCl₃ onto SiO₂ and CsPW followed by reduction with H₂ at 250 °C (ESI^†). This method gives supported bimetallic PtAu nanoparticles of a random composition together with various Pt and Au nanoparticles.^15,16,31 Information about the catalysts studied is given in

Palladium catalyst immobilized on functionalized microporous organic polymers for C–C coupling reactions

Two microporous organic polymer immobilized palladium (MOP-Pd) catalysts were prepared from benzene and 1,10-phenanthroline by Scholl coupling reaction and Friedel–Crafts reaction, respectively. The structure and composition of the catalyst were characterized by FT-IR, TGA, N₂ sorption, SEM, TEM, ICP-AES and XPS. MOP-Pd catalysts were found to possess high specific surface areas, large pore volume and low skeletal bone density. Moreover, the immobilized catalyst also had advantages, such as readily available raw materials, chemical and thermal stability, and low synthetic cost. The Pd catalyst is an effective heterogeneous catalyst for carbon–carbon (C–C) coupling reactions, such as the Heck reaction and Suzuki–Miyaura reaction, affording good to high yields. In these reactions, the catalyst was easily recovered and reused five times without significant activity loss.

Two microporous organic polymers were prepared from 1,10-phenanthroline by Scholl coupling reaction and Friedel–Crafts reaction, and applied to Heck reaction and Suzuki–Miyaura reaction as heterogeneous catalysts.

Carbon–carbon (C–C) coupling reactions have become one of the most versatile and utilized reactions for the selective construction of C–C bonds for the formation of functionalised aromatics,¹ natural products,² pharmaceuticals,³ polymers⁴ and advanced materials.⁵ Many transition metals have been used as catalysts in these reactions, aided by a great variety of ligands ranging from simple, commercial phosphines to complex custom-made molecules.⁶ Among these transition metals, palladium plays a significant role in various cross-coupling reactions, such as Suzuki,⁷ Heck,⁸ Sonogashira,⁹ Stille,¹⁰ and Ullmann coupling reactions,¹¹ due to their strong electrical and chemical properties.¹² Over the past decades, various homogeneous catalytic systems have been developed for organic transformations,¹³ which often progress smoothly under the inert atmosphere in organic solvents, for example, toluene or tetrahydrofuran in the presence of soluble palladium complexes as catalysts. However, most homogeneous palladium catalysts suffer from drawbacks such as high-cost of phosphine ligands, use of various additives, difficult separation, metal leaching, recovery, recyclability, and the toxicity of phosphine ligands.Heterogeneous catalysis have attracted increasing attention as they have been proven to be useful for different organic reactions owning to their unique properties, such as high reactivity, stability, easy separation, purification and recyclability.¹⁴ Many active heterogeneous palladium catalysts have been developed and widely applied in the C–C coupling reactions.¹⁵ Palladium has been immobilized on various solid supporting materials, such as zeolite,¹⁶ silica,¹⁷ metal organic frameworks,¹⁸ and functionalized graphene oxide.¹⁹ However, a substantial decrease in activity and selectivity of the heterogeneous palladium catalysts is frequently observed because of their long diffusion pathway to catalytic sites and the difference of electron density on active sites. To address these problems, materials with larger interface and more active site are employed to support palladium as heterogeneous catalysts, such as palladium immobilized on hyper-crosslinked polymers were high activity in Suzuki–Miyaura coupling reaction.²⁰Microporous organic polymers (MOPs) consists of purely organic elements have recently emerged as versatile platforms for heterogeneous catalysts thanks to their unique properties, including superior chemical, thermal and hydrothermal stability, synthetic diversity, low skeletal density and high surface area.^20,21 More importantly, the bottom–up approach of MOPs provides an opportunity for the design of polymer frameworks with a range of functionalities into the porous structure to use as catalysts or ligands.²² Recently, Kaskel reported the incorporation of a thermally fragile imidazolium moiety into MOPs resulted in a heterogeneous organocatalyst active in carbene-catalyzed Umpolung reaction.²³ Wang designed photocatalysts with microporous via the copolymerization from pyrene and dibenzothiophene-S,S-dioxide building blocks and tested the effect of the photocatalytic hydrogen evolution.²⁴ Xu described the synthesis of microporous with N-heterocyclic carbenes by an external cross-linking reaction and applied it in Suzuki reaction.²⁵ Zhou demonstrated for the first time that the microporous structure has a positive effect on controlling selectivities in the hydrosilylation of alkynes.²⁶ Recently, we also reported three pyridine-functionalized N-heterocyclic carbene–palladium complexes and its application in Suzuki–Miyaura coupling reactions.²⁷1,10-phenanthroline is an ideal candidate of ligands due to its structural features such as two N-atom placed in juxta position to provide binding sites for metal cations.²⁸ To utilize the unique structure feature, we employed it in the construction of MOPs via Scholl and Friedel–Crafts reaction, respectively. Therefore, this paper presents our recent studies on the synthesis of two heterogeneous palladium catalysts supported on MOPs through a simple and low-cost procedure. These catalysts displayed remarkable catalytic activity in C–C coupling reactions, including Suzuki–Miyaura reaction and Heck coupling reaction. The properties of simple preparation, wide application of this catalyst and good performance in C–C coupling reactions and adaptability with various substrates make it perfect catalytic option for C–C coupling reactions.The microporous network with 1,10-phenanthroline functional groups and incorporation of Pd metal were confirmed by Fourier transform infrared (FT-IR) spectroscopy. The FT-IR spectra of MOPs and MOPs-Pd (Fig. 1) displayed a series of bands around 2800–3100 cm⁻¹, which were assigned to the C–H stretching band and in-of-plane bending vibrations of the aryl rings. The bands around 1550–1750 cm⁻¹ were attributed to the –C N- stretching band. The bands around 1400–1450 and 850–700 cm⁻¹ were corresponded to the benzene and 1,10-phenanthroline skeletal stretching and the C–H out-of-plane bending vibrations of the aryl rings, respectively. The bond around 1495 cm⁻¹ in MOPs-I and MOPs-Pd-I is assigned to in-of-plane bending vibrations of CH₂, which indicated that 1,10-phenanthroline and benzene were linked by CH₂.Open in a separate windowFig. 1FT-IR spectra of MOPs and MOPs-Pd.The X-ray photoelectron spectroscopy (XPS) analysis of the MOPs-Pd is performed to investigate the coordination states of palladium species (Fig. 2). In Fig. 2, the Pd 3d XPS spectra of the MOPs-Pd-I catalysts reveal that Pd is present in the +2 oxidation state rather than in the metallic state. This is corresponding to the binding energy (B.E.) of 337.4 eV and 342.4 eV, which are assigned to be Pd 3d_5/2 and 3d_3/2 of Pd (+2), respectively. Compared with the PdCl₂ (337.9 eV and 343.1 eV), the Pd²⁺ binding energy in the MOPs-Pd-I catalyst shifts negatively by 0.5 eV and 0.7 eV. This can be attributed to the effect of the coordination with 1,10-phenanthroline in microporous networks. The results show that Pd²⁺ can be immobilized successfully on the MOPs by coordinating to 1,10-phenanthroline rather than by physical adsorption of Pd²⁺ on the surface. XPS graphs of MOPs-Pd-II also reveal that Pd²⁺ is immobilized on MOPs materials.Open in a separate windowFig. 2XPS spectra of the MOPs-Pd.The surface area and pore structure of the MOPs and MOPs-Pd were investigated by nitrogen adsorption analyses at 77.3 K. In Fig. 3, the MOPs-Pd exhibits type I adsorption–desorption isotherms, which is similar to the isotherms exhibited by the parent MOPs polymers. The result implies that these microporous organic polymers and metalized polymers consist of both micropores and mesopores. The apparent Brunauer–Emmett–Teller surface areas (S_BET) of MOPs-Pd are smaller than those of the non-metallized parent networks (Open in a separate windowFig. 3N₂ adsorption–desorption isotherms and corresponding pore size distributions of MOPs and MOPs-Pd.Physical properties of MOPs and MOPs-Pd

Enantioselective bromination of axially chiral cyanoarenes in the presence of bifunctional organocatalysts

Enantioselective bromination of axially chiral cyanoarenes bearing high intrinsic rotational barriers via dynamic kinetic resolution using bifunctional organocatalysts is reported. Sequential addition of a brominating reagent in several portions at an optimized temperature was effective in accomplishing high enantioselectivities.

Enantioselective bromination of axially chiral cyanoarenes bearing high intrinsic rotational barriers via dynamic kinetic resolution using bifunctional organocatalysts is reported.

Axially chiral biaryls are privileged structures in pharmaceuticals,¹ asymmetric catalysts,² functional materials,³etc. Thus, the development of efficient methods for their synthesis is desirable to advance research in these scientific fields. Among recent accomplishments on catalytic atroposelective transformations⁴ toward the synthesis of densely substituted axially chiral biaryls, powerful strategies include organocatalytic dynamic kinetic resolution involving ortho-functionalization of existing biaryls via the introduction of additional rotational barriers.⁵ In this method, substrates should in principle have rotational barriers low enough to enable fast rotation about the biaryl axis, leading to their rapid racemization. Therefore, it is difficult to employ biaryl substrates bearing intrinsic rotational barriers, which impede their racemization. In 2015, the Miller group reported an elegant example of this type of dynamic kinetic resolution via bromination of 3-arylquinazolin-4(3H)-ones, the rotational barrier of which is ∼19 kcal mol⁻¹, by slow addition of a brominating agent.^5e Here, we present enantioselective bromination of axially chiral cyanoarenes bearing intrinsic rotational barriers exceeding 18 kcal mol⁻¹ (Scheme 1). To the best of our knowledge, there has been no report of a catalytic asymmetric reaction affording axially chiral cyanoarenes,⁶ despite their prevalence in bioactive agents⁷ and the rich chemistry of cyano compounds as synthetic intermediates.⁸Open in a separate windowScheme 1Enantioselective bromination of axially chiral cyanoarenes using bifunctional organocatalysts. 9 Other catalysts 3d and 3e, bearing a cyclohexanediamine framework, and 3f, bearing a binaphthyl framework, resulted in poor enantioselectivities (10 Using 3a and 3c, lower reaction temperatures were investigated (Fig. 1) were also investigated; NBA (4a) still afforded the best enantioselectivities ( EntryCatalystBrominating reagentSolventTemp. (°C)Yield^b (%)ee (%)13aNBA (4a)CH₂Cl₂25812623bNBA (4a)CH₂Cl₂2587633cNBA (4a)CH₂Cl₂25891843dNBA (4a)CH₂Cl₂2583653eNBA (4a)CH₂Cl₂2585363fNBA (4a)CH₂Cl₂2579373aNBA (4a)CH₂Cl₂−40822083aNBA (4a)CH₂Cl₂−60<1—93cNBA (4a)CH₂Cl₂−408341103cNBA (4a)CH₂Cl₂−60<1—113cNBA (4a)CHCl₃−402154123cNBA (4a)Toluene−4018−10133cNBA (4a)THF−4013−2143cNBA (4a)Et₂O−4046−20153cNBA (4a)EtOAc−4068−4163cNBA (4a)EtOH−40<5—173cDBH (4b)CH₂Cl₂−40791183cNBS (4c)CH₂Cl₂−408220193cNBP (4d)CH₂Cl₂−4079−520^c,d3cNBA (4a)CH₂Cl₂−40854921^c,e3cNBA (4a)CH₂Cl₂−40515922^c,f3cNBA (4a)CH₂Cl₂−40336623^c,g3cNBA (4a)CH₂Cl₂−401771 Open in a separate window^aReactions were run using 1a (0.10 mmol), the brominating reagent (0.30 mmol), and the catalyst (0.010 mmol) in the solvent (10 mL).^bIsolated yields.^cReactions were run using 3c (0.0050 mmol).^dReaction was run for 48 h.^eReaction was run for 24 h.^fReaction was run for 12 h.^gReaction was run for 6 h.Open in a separate windowFig. 1Brominating reagents.Subsequently, to improve the efficiency of dynamic kinetic resolution by retarding the enantiodetermining bromination,^5e4a was added sequentially in five portions (Fig. 2).¹¹ Although the procedure hardly affected the results at −40 °C, the enantioselectivity was greatly improved for reactions carried out at −20 °C and −30 °C. Such effects were smaller at temperatures above −10 °C.Open in a separate windowFig. 2Investigations of temperatures and procedures. Blue bar: reactions were run with 4a added in 1 portion. Red bar: reactions were run with 4a added in 5 portions. Green values represent yields of 2a isolated after silica gel column chromatography. At 0, −10, −20, and −30 °C, reactions were run for 24 h; at −40 °C, reactions were run for 72 h.Next, at −30 °C and −40 °C, respectively, the relationships between enantioselectivity and yield were investigated (Fig. 3). Reactions were carried out using various amounts of 4a. At both temperatures, the enantioselectivity decreased as the yield increased; however, the quantitative reactions also exhibited some enantioselectivity (−30 °C: 99% yield, 50% ee; −40 °C: 99% yield, 47% ee), implying the presence of the characteristics of dynamic kinetic resolution. In addition, although the enantioselectivity was better at −40 °C than −30 °C when the yield was low, the relationship became reversed as the yield increased; hence, the efficiency of dynamic kinetic resolution was revealed to be better at −30 °C than at −40 °C. Furthermore, when 1.5 equiv. of 4a were used at −30 °C affording 2a in 22% yield with 65% ee, the ortho-monobrominated product 1a-Br (Fig. 4) was also obtained with 75% ee (see Scheme S1 in the ESI^† for details). It shows that the bromination at one of the ortho-positions introduces a rotational barrier high enough to set the chiral axis, which is consistent with the rotational barriers calculated at the M06-2X/6-311++G(2d,3p)//B3LYP/6-31+G(d,p) level of theory (Fig. 4).Open in a separate windowFig. 3Relationships between ee and yield. Red line: reactions were run at −30 °C for 24 h with 4a added in 5 portions. Blue line: reactions were run at −40 °C for 72 h with 4a added in 5 portions. Red and blue values represent amounts of 4a used for each reaction.Open in a separate windowFig. 4Rotational barriers of substrate, intermediate, and product calculated at the M06-2X/6-311++G(2d,3p)//B3LYP/6-31+G(d,p) level of theory.Under the conditions of using 3c as the catalyst at −30 °C with 3 equiv. of 4a added sequentially in five portions, other substrates bearing substituted phenols were also investigated (Scheme 2).¹² First, substrates 1b–1e bearing a substituent at the meta-position were investigated. While the electron-deficient substrate 1b resulted in poor enantioselectivity, 1c and 1d bearing aliphatic substituents gave improved enantioselectivities; however, substrate 1e with a methoxy group resulted in low enantioselectivity. In addition, substrates 1f–1i bearing substituents at the para-positions of the biaryl axis were then examined; phenol 2h bearing a methyl group resulted in higher enantioselectivities than phenols 2f and 2g bearing electron-withdrawing groups and 2i bearing a methoxy group. These results suggest that aliphatic substituents might efficiently facilitate the racemization of 1 during bromination, leading to dynamic kinetic resolution with greater enantioselectivity. Utilizing this methodology with the characteristics of dynamic kinetic resolution, the reactions of 1c and 1g were also carried out using a sub-stoichiometric amount of 4a (Scheme 3); higher enantioselectivities were accomplished albeit with lower yields.¹³ The absolute configuration of 2c was determined by X-ray crystallography (see the ESI^† for details), and the configurations of all other products were assigned analogously.Open in a separate windowScheme 2Reactions of substrates with substituted phenols. ^aReaction was run for 72 h.Open in a separate windowScheme 3Reactions with a substoichiometric amount of 4a.In summary, we present enantioselective bromination of axially chiral cyanoarenes bearing high intrinsic rotational barriers via dynamic kinetic resolution using bifunctional organocatalysts. The sequential addition of 4a in several portions at the optimized temperature was effective in improving the enantioselectivity. Although the enantioselectivities are still moderate using the current catalytic system, the guidelines for designing catalytic asymmetric syntheses of axially chiral cyanoarenes were established. Further studies on the additional optimization and application of this methodology to the construction of densely substituted axially chiral biaryls are currently underway.     

A mild one-pot synthesis of 2-iminothiazolines from thioureas and 1-bromo-1-nitroalkenes

A mild method to access functionalized 2-iminothiazolines in a facile and efficient manner has been developed. The reaction started from 1,3-disubstituted thioureas and 1-bromo-1-nitroalkenes in the presence of triethylamine in THF and proceeded smoothly in air to afford 2-iminothiazoline derivatives in moderate to good yields.

A mild method to access functionalized 2-iminothiazolines in a facile and efficient manner has been developed.

Functionalized 2-iminothiazoline has been an important building block in organic chemistry.¹ Its derivatives show significant pharmacological activities such as bactericidal and fungicidal activity.² In addition, they are found in drug applications for treatment of allergies, hypertension, inflammations, bacterial and HIV infections.³ Pifithrin (Pft-α) (Fig. 1), isolated by screening of chemical libraries using 2-iminothiazoline skeleton, is a lead compound for p53 inactivation and has received increasing attention due to its possible applications in therapy of Alzheimer''s disease, Parkinson''s disease, stroke and other pathologies related to various signalling pathways.⁴ Hence, its utility and applicability are widely recognized in organic and biological areas.Open in a separate windowFig. 1Pharmacologically important molecules consisting of 2-iminothiazoline core structure. (a) p53 inactivator; (b) skin whitening agent; (c) anti-inflammatory agent.The classical synthesis of 2-aminothiazole moiety involves the Hantzsch condensation reaction of thioureas and α-haloketones.⁵ Birkinshaw et al. reported the synthesis of N-alkylated imino-thiazolines by replacing thioureas with mono-N-substituted thioureas.⁶ Also, several alternative strategies have been devised, which include synthesis of highly functionalized thiazoles and 2-iminothiazolines by replacing α-haloketone with 2,2-dicyano-3,3-bis(trifluoromethyl)oxirane⁷ and 2-chlorooxirane,⁸ treatment of α-bromoketimines with potassium thiocyanate,⁹ reaction of N-monoalkylated thioureas with 3-bromomethyl-2-cyanocinnamonitrile,¹⁰ cycloadditions followed by elimination of 5-imino-1,2,4-thiazolidin-3-ones with enamines and ester enolate,¹¹ ring transformation of 1-arylmethyl-2-(thiocyanomethyl)aziridines in the presence of TiCl₄ and acyl chloride,¹² reaction of N-propargylaniline with acyl isothiocyanates.¹³ Less general approaches towards the synthesis of these compounds involve the reaction of ketone either with N-alkyl rhodanamine or bisbenzyl formamidine disulfide¹⁴ or the reaction of α-chloroketones with thiosemicarbazide in an acidic medium,¹⁵ condensation of α-haloketones with N-benzoyl-N′-arylthioureas or N,N′-disubstituted thioureas.¹⁶Although some of the methods used for preparing 2-iminothiazolines are convenient and effective, most procedures reported in literatures require arduous preparation of precursor substrates or harsh reaction conditions. Till now, only a few procedures on the one-pot synthesis of 2-iminothiazoline from N,N′-dialkylthiourea and in situ generated α-bromoketones have been reported.¹⁷ Herein, we reported a novel and efficient methodology for the synthesis of 2-imino-5-nitrothiazolines using 1,3-diarylthioureas and 1-bromo-1-nitroalkenes as starting materials.The β-bromo-β-nitrostyrenes, with β-disubstituted styrene structure, showed versatile reactivity as a trifunctional synthon. Previous literatures showed their activity as Michael acceptors and [3 + 2] and [4 + 2] cycloaddition partners.¹⁸ In our preliminary experiments, the reaction of 1,3-diphenylthiourea and β-bromo-β-nitrostyrene 1a was studied, while the latter one could easily be prepared according to the reported procedure.^18e We found that when these two reactants were treated with base such as K₂CO₃ in THF at room temperature under atmospheric air, a red crystalline product was obtained ( Entry^aBaseSolventTemperature (°C)Time (h)Yield (%)1K₂CO₃THFrt24622^bK₂CO₃THF7010603Et₃NTHFrt24724^bEt₃NTHF7010655DBUTHFrt24636^bDBUTHF7010587KHCO₃THFrt24558^bKHCO₃THF7010609DIPEATHFrt246810NoneTHFrt242911^cEt₃NTHFrt246412^dEt₃NTHFrt245813^eEt₃NTHFrt241714Et₃NCH₂Cl₂rt244515Et₃NToluenert244216^bEt₃NToluene110540Open in a separate window^aReactions were performed with β-bromo-β-nitrostyrene 1a (0.10 mmol) and 1,3-diphenylthiourea 2a (0.11 mmol) with base (0.02 mmol) in the indicated solvent (2.0 mL) under atmospheric air.^bβ-Bromo-β-nitrostyrene was completely consumed.^cReaction was carried out with 0.04 mmol of base.^dReaction was carried out with 0.01 mmol of base.^eReaction was carried out with 0.1 mmol of base.This structure was later confirmed by single crystal X-ray analysis as shown in Fig. 2. When the reaction temperature was increased to 70 °C, the reaction was completed in shorter time. However, the yield was lower due to an increase of side products (Open in a separate windowFig. 2X-ray crystallography of compound 3a.Several other bases were tested such as K₂CO₃, Et₃N, DBU, KHCO₃, DIPEA, and Et₃N was found to give the best results ( Open in a separate window^aReactions were performed with 1-bromo-1-nitroalkenes 1a–1n (0.10 mmol) and 1,3-diarylthioureas 2 (0.11 mmol) with Et₃N (0.02 mmol) in THF (2.0 mL) at room temperature in the air for 24 hours.A plausible mechanism for this reaction has been proposed as shown in Scheme 1. Initially, a typical Michael addition happens with the β-bromo-β-nitrostyrene 1a,¹⁹ which is initiated by the attack of lone pair of nitrogen atom in 1,3-diphenylthiourea 2a, affording intermediate II. The successive tautomerism of thiourea structure and nucleophilic substitution in intermediate II generates five-membered ring intermediate III. Deprotonation of intermediate III by preceding bromide ion affords intermediate IV which subsequently undergoes aromatization with aid of atmospheric oxygen,²⁰ yielding final product 3a.Open in a separate windowScheme 1Plausible reaction pathway.     

One-pot reductive amination of carbonyl compounds with nitro compounds over a Ni/NiO composite

Easily prepared Ni/NiO acts as a heterogeneous catalyst for the one-pot reductive amination of carbonyl compounds with nitroarenes to afford secondary amines with H₂ as a hydride source. This catalytic system does not require a special technique to avoid air-exposure, in contrast to the common heterogeneous Ni catalysts.

Easy-to-prepare Ni/NiO acts as an efficient heterogeneous catalyst for one-pot reductive amination of carbonyl compounds with nitroarenes.

Amines are among the most important organic compounds for the chemical, materials, pharmaceutical and agrochemical industries.¹ In particular, aromatic and heteroaromatic amines occupy a privileged position in medicinal chemistry,^1c,2 as exemplified in top-selling drugs such as atorvastatin, hydrochlorothiazide, furosemide and acetaminophen.³ The general methods to prepare aryl and heteroaryl amines are the reductive amination of carbonyl compounds,⁴ direct alkylation of amines with alkyl halides,⁵ Buchwald–Hartwig amination⁶ and Ullman-type C–N bond formation.⁷ These amination systems utilize aniline derivatives which are usually prepared in advance by hydrogenation of nitroarenes.⁸ Direct amine synthesis using nitroarenes is attractive because it eliminates the hydrogenation step, which saves time, energy and cost. Among the amination reactions, reductive amination has been actively investigated due to its high atom economy and ease of industrial application (Scheme 1);⁹ however, reductive amination has frequently been accompanied by unwanted side products due to the reduction of carbonyl compounds to alcohols and/or over-alkylation of product amines. One-pot reductive amination with nitro compounds has been achieved by precious metal catalysis.¹⁰ Recently, precious metal alloy nanoparticles were demonstrated to exhibit high catalytic performance for one-pot reductive amination with nitro compounds, even under mild reaction conditions.¹¹ In the context of economic efficiency and a ubiquitous element strategy, the replacement of precious metals with earth-abundant metals has gained much attention. Although some catalytic systems based on Fe,¹² Cu,¹³ Co ¹⁴ and Mo ¹⁵ have been reported using H₂ as a reductant, severe reaction conditions are typically required (Table S1, ESI^†). It is noteworthy that the nitrogen-doped carbon supported cobalt catalysts were reported to be active for one-pot reductive amination using nitroarenes using formic acid or CO/H₂O as a reductant though high temperature was required (Table S2, ESI^†).¹⁶Open in a separate windowScheme 1One-pot reductive amination using nitroarenes.To develop active catalysts for one-pot reductive amination using nitro compounds, we have focused on nickel catalysts, which are known as active catalysts for many transformation reactions.^17,18 The active species is typically metallic nickel, which is easily oxidized in air and becomes covered with NiO.¹⁹ Therefore, special techniques to avoid air-exposure (i.e., pre-reduction in the reaction vessel, glovebox) are required to achieve high catalytic performance for liquid phase reactions. Herein we report an easily prepared Ni/NiO composite as a heterogeneous catalyst for one-pot reductive amination using nitro compounds. This Ni catalyst can be handled under an air atmosphere, even though the supposedly active species, metallic nickel, is oxidized by air-exposure.Ni/NiO was prepared by the partial reduction of NiO with H₂ in the temperature range from 200 to 500 °C (Ni/NiO-X: X = reduction temperature). X-ray diffraction (XRD) patterns of the prepared Ni catalysts after exposure to air are summarized in Fig. 1(A). When NiO is treated in H₂ at 200 °C, the dominant phase produced is still nickel oxide. Metallic nickel was formed by reduction at ≥250 °C, which is consistent with the H₂-temperature programmed reduction (H₂-TPR) profile of NiO in which the H₂ consumption peak begins to increase at around 250 °C.²⁰ The ratio of Ni to NiO, determined by Rietveld analysis, increased with increasing reduction temperature and no peaks attributed to metallic nickel were evident for Ni/NiO-500 (†) and crystallite diameter estimated from (111) diffraction lines using Scherrer''s equation (Table S3, ESI^†). Fig. 1(C) shows an SEM image of Ni/NiO-300, where the particle size was estimated to be 0.5–3 μm, and the layered structure of NiO was maintained after the reduction treatment (see also Fig. S4, ESI^†).Open in a separate windowFig. 1(A) XRD patterns for Ni/NiO-X; (a) Ni/NiO-500, (b) Ni/NiO-400, (c) Ni/NiO-350, (d) Ni/NiO-300, (e) Ni/NiO-250, and (f) Ni/NiO-200 (♦: Ni, ○: NiO), and (B) SEM images of Ni/NiO-300.Specific surface areas and weight ratios of Ni to NiO

Mesoporous PbO nanoparticle-catalyzed synthesis of arylbenzodioxy xanthenedione scaffolds under solvent-free conditions in a ball mill

A protocol for the efficient synthesis of arylbenzodioxy xanthenedione scaffolds was developed via a one-pot multi-component reaction of aromatic aldehydes, 2-hydroxy-1,4-naphthoquinone, and 3,4-methylenedioxy phenol using mesoporous PbO nanoparticles (NPs) as a catalyst under ball milling conditions. The synthesis protocol offers outstanding advantages, including short reaction time (60 min), excellent yields of the products (92–97%), solvent-free conditions, use of mild and reusable PbO NPs as a catalyst, simple purification of the products by recrystallization, and finally, the use of a green process of dry ball milling.

An efficient one-pot multicomponent protocol was developed for the synthesis of arylbenzodioxy xanthenedione scaffolds using mesoporous PbO nanoparticles as reusable catalyst under solvent-free ball milling conditions.

Recently, the ball milling technique has received great attention as an environmentally benign strategy in the context of green organic synthesis.^1a The process of “ball milling” has been developed by adding mechanical grinding to the mixer or shaker mills. The ball milling generates a mechanochemical energy, which promotes the rupture and formation of the chemical bonds in organic transformations.^1b Subsequently, detailed literature^1c and books on this novel matter have been published.^2a,b Several typical examples include carbon–carbon and carbon–heteroatom bond formation,^2c organocatalytic reactions,^2d oxidation by using solid oxidants,^2e dehydrogenative coupling, asymmetric, and peptide or polymeric material synthesis, which have been reported under ball milling conditions.^2e Hence, the organic reactions using ball milling activation carried out under neat reaction environments, exhibit major advantages,^2f including short reaction time, lower energy consumption, quantitatively high yields and superior safety with the prospective for more improvement than the additional solvent-free conditions and clear-cut work-up.^3–5On the other hand, the organic transformations using metal and metal oxide nanoparticles⁶ are attracting enormous interest due to the unique and interesting properties of the NPs.^7,8,9a Particularly, PbO NPs^9b provide higher selectivity in some organic reactions^9c and find applications in various organic reactions, like Paal–Knorr reaction,¹⁰ synthesis of diethyl carbonate,¹¹ phthalazinediones,¹² disproportionation of methyl phenyl carbonate to synthesize diphenyl carbonate,¹³ the capping agent in organic synthesis, and selective conversion of methanol to propylene.¹⁴ In addition, the PbO NPs are also used in many industrial materials.^15,16However, till date, PbO NPs have not been explored in MCRs leading to biologically important scaffolds. Among others, the xanthene scaffolds¹⁷ are one of the important heterocyclic compounds¹⁸ and are extensively used as dyes, fluorescent ingredients for visual imaging of the bio-molecules, and in optical device technology because of their valuable chemical properties.¹⁹ The xanthene molecules have conjointly been expressed for their antibacterial activity,²⁰ photodynamic medical care, anti-inflammatory drug impact, and antiviral activity. Because of their various applications, the synthesis of these compounds has received a great deal of attention.²¹ Similarly, vitamin K nucleus^22,23 shows a broad spectrum of biological properties, like anti-inflammatory, antiviral, antiproliferative, antifungal, antibiotic, and antipyretic.^24a As a consequence, a variety of strategies^24b have been demonstrated in the literature for the synthesis of xanthenes and their keto derivatives, like rhodomyrtosone-B,^25a rhodomyrtosone-I,^25b and BF-6 ^25c as well as their connected bioactive moieties. Few biologically active xanthene scaffolds are shown in (Fig. 1).Open in a separate windowFig. 1Some biologically important xanthenes and their keto derivatives.Due to the significance of these compounds, the synthesis of xanthenes and their keto derivatives using green protocols is highly desirable. Reported studies reveal that these scaffolds are synthesized by three-component condensations using p-TSA²⁶ and scolecite²⁷ as catalysts. However, these methods suffer from the use of toxic acidic catalysts like p-TSA, long reaction times (3 h), harsh refluxing²⁶ or microwave reaction conditions,²⁷ and tedious work-up procedures. The previously reported methods for the synthesis of xanthenediones are shown in Scheme 1.Open in a separate windowScheme 1Previous protocol for the synthesis of xanthenedione derivatives.Herein, we report an economical and facile multicomponent protocol, using ball milling, for the synthesis of 7-aryl-6H-benzo[H][1,3]dioxolo[4,5-b]xanthene-5,6(7H)-dione using PbO NPs as a heterogeneous catalyst (Scheme 2). The PbO NPs are non-corrosive, inexpensive, and easily accessible.Open in a separate windowScheme 2General reaction scheme of PbO NP-catalyzed synthesis of the xanthenedione scaffolds under ball milling conditions.In our protocol,²⁸ the PbO NPs were initially prepared by mixing sodium dodecyl sulphate (2.5 mmol) and sodium hydroxide (10 mL, 0.1 N) with an aqueous methanolic solution of lead nitrate (2 mmol) under magnetic stirring at 30 °C by continuing the reaction for 2 h. Then, the obtained white polycrystalline product was filtered, washed with H₂O, and dried at 120 °C, followed by calcination at 650 °C for 2 h. During this step, the white PbO NPs turned pale yellow in colour. Eventually, the synthesized PbO was then characterized by spectroscopic and analytical techniques.The powder X-ray diffraction (XRD) pattern revealed the crystalline nature of the PbO NPs as the diffraction peaks corresponding to (131), (311), (222), (022), (210), (200), (002), and (111) crystal planes were identified (Fig. 2). The XRD outline of the synthesized PbO NPs was further established for the formation of space group Pca2₁ ²⁹ with a single orthorhombic structure (JCPDS card number 76-1796). The sharp diffraction peaks indicated good crystallinity, and the average particle size of the PbO NPs was estimated to be 69 nm, as calculated using the Debye–Scherer equation.Open in a separate windowFig. 2The powder XRD pattern of PbO NPs.The surface morphology of the PbO NPs was analyzed by scanning electron microscopy (SEM), and the SEM image revealed the discrete and spongy appearance of the PbO NPs (Fig. 3).Open in a separate windowFig. 3The SEM image of PbO NPs.Moreover, the elemental composition obtained from energy dispersive X-ray (EDX) analysis confirmed that the material contains Pb and O elements, and no other impurity was present (Fig. 4).Open in a separate windowFig. 4The EDAX spectrum of crystalline PbO NPs.The transmission electron microscopy (TEM) image shown in Fig. 5 indicated the formation of orthorhombic crystallites of PbO with several hexagon-shaped particles. The dark spot in the TEM micrograph further confirmed the synthesis of PbO NPs, as the selected area diffraction pattern associated with such spots reveals the occurrence of the PbO NPs in total agreement with the X-ray diffraction data (Fig. 6). The average size of the PbO nanocrystals by TEM was approximated to be around 20 nm.Open in a separate windowFig. 5The TEM image of nanocrystalline PbO NPs.Open in a separate windowFig. 6The SAED image of nanocrystalline PbO NPs.The Fourier transform infrared (FT-IR) spectrum (ESI, S6^†) of the PbO NPs displayed peaks at 575, 641, and 848 cm⁻¹, which corresponds to the Pb–O vibrations. Furthermore, the absorption band at ∼3315 cm⁻¹ was due to the presence of the hydroxyl group (–OH) in the NPs.The N₂ adsorption–desorption isotherms of the PbO nanoparticles shown in Fig. 7 was consistent with type IV adsorption–desorption isotherms with H1 hysteresis corresponding to the cylindrical mesoporous structure. Moreover, the surface area, pore-volume, and BJH pore diameter were found to be 32.0 m² g⁻¹, 0.023 cm³ g⁻¹, and 30.9 Å, respectively.Open in a separate windowFig. 7BET surface area and pore size of nanocrystalline PbO catalyst.The catalytic activity of the synthesized PbO NPs was tested in a one-pot multicomponent synthesis of arylbenzodioxoloyl xanthenedione derivative under ball milling condition according to the reaction scheme 2a, with 3,4-dimethoxybenzaldehyde (166.2 mg, 1.0 mmol), 3,4-methylenedioxyphenol (138.0 mg, 1.0 mmol), and 2-hydroxy-1,4-naphthoquinone (174.0 mg, 1.0 mmol) as reactants. The reaction conditions, the ball milling parameters (speed, time, and ball to solids ratio), and the PbO nanocatalyst amount were first optimized to produce the highest yield using experimental design as shown in EntryConditionsRotation (rpm)Catalyst (mol%)Time (min)Yield (%)^a1Ball milling4000050212Ball milling4001050483Ball milling4001560544Ball milling4002070595Ball milling5001050626Ball milling5001550657Ball milling5002060678Ball milling6001070719Ball milling60015507710Ball milling60020608211Ball milling60005709012Ball milling600105091 13 Ball milling ^b 600 15 60 97 14Ball milling60020709715No ball milling^c—1560—Open in a separate window^aIsolated yield; model reaction: 3,4-dimethoxybenzaldehyde (166.2 mg, 1.0 mmol), 3,4-methylenedioxyphenol (138.1 mg, 1.0 mmol), 2-hydroxy-1,4-naphthoquinone (174.1 mg, 1.0 mmol) under ball milling.^bOptimized reaction conditions.^cThe reaction was performed under stirring condition in a RB flask.Next, by utilizing the general experimental procedure (ESI^† for detail experimental procedure; S2) and the aforementioned optimized conditions (29 we also investigated the possible scopes of the reactants as revealed in 26 These data are available in S4 (see ESI^† for the spectroscopic data). The aromatic aldehydes comprising both electron-withdrawing (e.g., nitro group) and electron-donating (e.g., –OMe, –OH, –Cl, –Me, and –Br) groups participated proficiently in the reaction without including any electronic effects. The aromatic aldehyde with electron-donating groups (e.g., –OMe, –OH, –Cl, –Me, and –Br) increased the product yield, while in the case of aryl aldehyde having an electron-withdrawing group (e.g., –NO₂), both the product yield as well as the reaction rate decreased. These findings are depicted in †Scope of the PbO NP-catalyzed synthesis of arylbenzodioxoloyl xanthenedione derivatives

Boron nitride nanochannels encapsulating a water/heavy water layer for energy applications

Water interaction and transport through nanochannels of two-dimensional (2D) nanomaterials hold great promises in several applications including separation, energy harvesting and drug delivery. However, the fundamental underpinning of the electronic phenomena at the interface of such systems is poorly understood. Inspired by recent experiments, herein, we focus on water/heavy water in boron nitride (BN) nanochannels – as a model system – and report a series of ab initio based density functional theory (DFT) calculations on correlating the stability of adsorption and interfacial properties, decoding various synergies in the complex interfacial interactions of water encapsulated in BN nanocapillaries. We provide a comparison of phonon vibrational modes of water and heavy water (D₂O) captured in bilayer BN (BLBN) to compare their mobility and group speed as a key factor for separation mechanisms. This finding, combined with the fundamental insights into the nature of the interfacial properties, provides key hypotheses for the design of nanochannels.

Single layer water (SLW) on BN layer and encapsulated between bilayer BN (BLBN) as nanochannel.

Hexagonal boron nitride (h-BN) is a synthetic material, similar to graphene in structure and layered form,^1,2 but with alternating B and N atoms. Among others properties, h-BN is considered for its hydrophobicity, remarkable chemical and thermodynamic stability (air stable up to 1000 °C),³ and exceptional mechanical⁴ and optical properties.⁵ Thin BN sheets have been fabricated by high-energy electron beam irradiation,⁶ ultrasonication,⁷ Lewis acid–base,⁸ hydrolysis of lithium based materials,⁹ liquid alloys of alkali metals at room temperature¹⁰ and chemical vapor deposition² methods.Nanochannels by design is an appealing idea due to their potential applications in filtration and separation as well as molecular sieving.^11,12 Recently, Agrawal et al.¹³ revealed the water phase transition encapsulated within carbon nanotubes of different radius. Specifically, fabricating artificial capillaries for molecular transport led to emergence of nanofluidics.¹⁴ Shultz et al.¹⁵ studied the local water structure by investigation of local and long-range response of hydrogen-bond network of water with surface. Water is polar due to the high electronegativity of oxygen atom and two weakly electropositive hydrogen atoms besides the buckled structure.¹⁶ Graphene-based materials such as graphene oxide (GO) membranes can have nanometer pores and tunable sieving of ions,¹² indicating low frictional water flow. Sun et al.¹⁷ studied on electro/magneto modulated ion transport through GO membranes. While several experimental works demonstrate promising applications of nanochannels, the fundamental subatomic and electronic phenomena at the heart of such nanochannels are poorly understood.Herein, we present a comprehensive ab initio study to decode the complex interfacial interactions of water and heavy water encapsulated in bilayer BN (BLBN) as a model system. Our findings demonstrated that 2D BN can be used as nanochannels with tunable interlayer distance that is determined by in/out-plane hydrogen bonds of water layers. To discover the mechanism for separating water and heavy water, we further investigate phonon spectrum for water layers between BLBN and for heavy water, deuterium oxide D₂O. This nanometer-scale BN capillaries is a flagship architecture in fabricating atomically channels for nanofluidic technology.¹⁸BN nanosheet could be a good candidate for water cleaning and purification as experimentally has been reported by Lei, et al.¹⁹ Moreover, Hao et al. in their paper²⁰ reported the properties of atomic layer deposition (ALD) boron nitride nanotube, which is relevant for water purification. Li et al.²¹ reported that porous boron nitride nanosheets show an excellent performance for water purification.More recently Falin et al.²² synthesized single crystalline of mono/few layer BN nanosheets. They experimentally measured the Young''s modulus of high quality 1–9 layer BN.²¹ Mechanical properties of BN nanosheets placed them among the strongest insulating materials, indicating the fracture strength of 70.5 ± 5.5 GPa.²¹To obtain fundamental insights on the interfacial interactions, a series of DFT calculations were performed on single layer water (SLW) molecules and double layer water (DLW) molecules settled on BN layers and encapsulated in BLBN (see Methods). We first examined the molecular models of SLW settled on BN layers with and without external field. Fig. 1a and b show SLW/BN, including (H₂O)₁₆, representing 16 water molecules and the substrate containing 120 B, N atoms. In order to take into account the effect of structural boundary conditions and compare the interfacial properties of SLW and DLW on BN surface, we employed the energy minimized structures for the SLW and DLW on BN layer (Fig. 1d and e), containing 32H₂O molecules. The electrical dipole moment (Open in a separate windowFig. 1Optimized single layer water (SLW)/BN and its electronic band structure for different external electric field, (a) E = 0 V Å⁻¹, (b) Total density of states (DOS) and (c) projected DOS for SLW/BN. Optimized double layer water (DLW)/BN and its electronic band structure for different external electric field, (d) E = 0, (e) E = 0.1 V Å⁻¹, (f) total DOS for nanochannels of (a) and (b).DFT results of interfacial properties of optimized SLW and DLW on BN

Palladium supported on triazolyl-functionalized hypercrosslinked polymers as a recyclable catalyst for Suzuki–Miyaura coupling reactions

A novel hypercrosslinked polymers-palladium (HCPs-Pd) catalyst was successfully prepared via the external cross-linking reactions of substituted 1,2,3-triazoles with benzene and formaldehyde dimethyl acetal. The preparation of HCPs-Pd has the advantages of low cost, mild conditions, simple procedure, easy separation and high yield. The catalyst structure and composition were characterized by N₂ sorption, TGA, FT-IR, SEM, EDX, TEM, XPS and ICP-AES. The HCPs were found to possess high specific surface area, large micropore volume, chemical and thermal stability, low skeletal bone density and good dispersion for palladium chloride. The catalytic performance of HCPs-Pd was evaluated in Suzuki–Miyaura coupling reactions. The results show that HCPs-Pd is a highly active catalyst for the Suzuki–Miyaura coupling reaction in H₂O/EtOH solvent with TON numbers up to 1.66 × 10⁴. The yield of biaryls reached 99%. In this reaction, the catalyst was easily recovered and reused six times without a significant decrease in activity.

A novel hypercrosslinked polymer-palladium catalyst was prepared via external cross-linking reactions and applied in Suzuki–Miyaura reactions as a recyclable catalyst, resulting in TON numbers up to 1.66 × 10⁴ and yields reaching 99%.

Heterogeneous catalysts are an attractive and versatile tool in industrial and academic research laboratories because of their unique properties,¹ which include high reactivity, stability, easy separation, purification and good recyclability.² Currently, heterogeneous catalysis represents an important field of research in green chemistry³ that receives frequent attention and witnessed constant development in recent years. However, heterogeneous catalysts normally have inferior catalytic efficiency compared to homogeneous systems because of their long diffusion pathways to catalytic sites and the difference in electron density on active sites.⁴ In addition, most recovered heterogeneous catalysts suffer from the sintering and leaching of metals, the loss of surface area and degradation after several reactions under typical reaction conditions.⁵ These drawbacks could be overcome by using appropriate catalyst supports that provide a large reaction surface with a proper porous structure.⁶Hypercrosslinked polymers (HCPs), a type of microporous organic polymer (MOP), are good support materials for noble metals to form heterogeneous catalysts.^6a,7 HCPs have a large number of permanent pores formed by extensive chemical crosslinking. Compared to other MOPs prepared by noble metal-based catalysts such as Pd, Pt and Ru, the preparation of HCPs is mainly based on acid-catalysed Friedel–Crafts alkylation reactions,⁸ which provide quick cross-linking to form strong linkages. These linkages lead to highly crosslinked networks with predominant porosity,⁹ resulting in extremely rigid networks that are difficult to collapse.¹⁰ Regarding the synthetic methodology, HCPs are mainly prepared by three methods.^6a The first method involves post-crosslinked polymer precursors.¹¹ The Davankov resins, which are the first examples of HCPs, were prepared by Davankov in the 1970s via post-crosslinking with external crosslinking agents.¹² The second method is the one-step polycondensation of functional monomers.¹³ Recently, the design and synthesis of hypercrosslinked polystyrene and their applications have undergone rapid development. For example, Yang designed microporous polytriphenylamine networks via the oxidative polymerization of triphenylamine and DCX crosslinkers.¹⁴ The third method is external cross-linking reaction.¹⁵ Tan developed the knitting strategy using formaldehyde dimethyl acetal as an external crosslinker to combine with rigid aromatic building blocks through the Friedel–Crafts reaction.¹⁶ Recently, our group synthesized three HCPs based on pyridine-functionalized N-heterocyclic carbene via an external cross-linking reaction and applied them in Suzuki–Miyaura coupling reactions.¹⁷ We then prepared HCPs using the readily available raw material, phenanthroline, and used it to catalyse the Heck reaction with good effect.¹⁸ HCPs have been widely used in catalysis, gas storage and separation, and drug release because of the following merits:¹⁹ (i) large surface areas and pores; (ii) superior chemical and thermal stability; and (iii) low cost and simple and versatile synthetic approach.1,2,3-Triazoles are one of the most important classes of N-heterocyclic compounds; they have been widely applied in pharmaceutical drugs,²⁰ bioconjugation,²¹ catalysts,²² materials²³ and synthetic organic chemistry.²³ Due to the large dipole moment in the 1,2,3-triazole unit, many reports have found that 1,2,3-triazoles can coordinate with metals.²⁴ This property gives 1,2,3-triazoles an important role in the field of catalysis, especially heterogeneous catalysis.²⁵In this paper, we report the preparation of hypercrosslinked polymers-palladium (HCPs-Pd) catalysts based on substituted 1,2,3-triazoles via external cross-linking reaction (Fig. 1) along with the utilization of the HCPs-Pd in Suzuki–Miyaura coupling reactions as a recyclable catalyst with high TON number. HCPs-Pd is simply prepared with low cost, mild conditions and easy separation. The catalyst possesses recyclability, high activity and excellent yield, making it useful for Suzuki–Miyaura coupling reactions.Open in a separate windowFig. 1The structures of HCPs and HCPs-Pd.The surface area and pore structure of the HCPs and HCPs-Pd were investigated by nitrogen adsorption analyses at 77.3 K. The nitrogen adsorption and desorption isotherms of the HCPs exhibit type I adsorption–desorption isotherms (Fig. 2), similar to the isotherms of HCPs-Pd. The isotherms show steep nitrogen gas adsorption at low relative pressure (P/P₀ < 0.05), which reflects abundant micropores in the polymers. Meanwhile, a slight hysteresis loop indicates the presence of some mesopores, and a sharp rise at high pressure (P/P₀ = 0.9–1.0) implies a spot of macropores in these materials. The apparent Brunauer–Emmett–Teller surface area (S_BET) of the HCPs (794 m² g⁻¹) is larger than that of HCPs-Pd (731 m² g⁻¹), which can be attributed to the partial filling of the pores in HCPs-Pd with metal (Fig. 2). The similar pore sizes of the HCPs and HCPs-Pd implies that the immobilization of palladium on the ESI^† did not change the pore-size distribution. The presence of some mesopores and macropores in HCPs-Pd is also essential because they could enable the heterogeneous catalysts upon soaking in a certain solvent. As a result, the catalytically active sites would better contact the substrates. The content of Pd in HCPs-Pd was detected by ICP analysis (Open in a separate windowFig. 2N₂ adsorption–desorption isotherms and the corresponding pore size distributions of HCPs and HCPs-Pd.Physical properties of HCPs and HCPs-Pd

Sodium borohydride-nickel chloride hexahydrate in EtOH/PEG-400 as an efficient and recyclable catalytic system for the reduction of alkenes

An efficient, safe and one-pot convenient catalytic system has been developed for the reduction of alkenes using NaBH₄–NiCl₂·6H₂O in EtOH/PEG-400 under mild conditions. In this catalytic system, a variety of alkenes (including trisubstituted alkene α-pinene) were well reduced and the Ni catalyst could be recycled.

An efficient, safe and one-pot convenient catalytic system has been developed for the reduction of alkenes using NaBH₄–NiCl₂·6H₂O in EtOH/PEG-400 under mild conditions.

The reduction of alkenes is an important transformation in organic synthesis, widely used particularly in petrochemical, pharmaceutical, and fine chemical processes. Traditionally, direct hydrogenation,^1–4 catalytic hydrogen transfer ^5–7and hydride reduction methods^8–10 have been employed for the reduction of alkenes. Among the reported methods, the utility of sodium borohydride for the reduction of simple alkenes first described by Brown in 1962 is well known.¹¹ In recent years, several related catalytic systems on modification of Brown''s approach have been developed. These catalytic systems include NaBH₄/NiCl₂·6H₂O/moist alumina in hexane,¹² InCl₃–NaBH₄ reagent system,¹³ NaBH₄/RuCl₃ under aqueous conditions,¹⁴ NaBH₄/CH₃COOH in the presence of Pd/C¹⁵ and NaBH₄-RANEY® nickel system in water.¹⁶ Nevertheless, most of these systems require costly transition metal catalyst, long reaction time and a large excess of NaBH₄. In addition to this, little has been done to recycle the catalyst for the reduction of alkenes using NaBH₄. Thus, a very simple, efficient and recyclable system for the reduction of alkenes by NaBH₄ would be highly desirable.In the reduction of alkenes by NaBH₄, the in situ generated metal nanoparticles (NPs) from the combination of appropriate metal salts and NaBH₄ catalyze the reduction of alkene.¹⁵ In general, metal NPs tend to agglomerate during the catalytic processes and therefore need to be protected by stabilizers.¹⁷ Castro et al. ever noticed the aggregation of NPs after just one time in the reduction of alkenes by NaBH₄ without use of a stabilizer.¹⁸ Immobilized nanoparticles (NPs) on insoluble solid supports were generally used for this process in the past literature.^12,15,16 One significant example was that Takashi Morimoto and coworkers reached 90% yield of ethylbenzene within 3 h using NiCl₂·6H₂O on moist alumina reducted by NaBH₄ in hexane at 30 °C.¹² Unfortunately, heterogeneous catalysts of NPS on solid supports are often more inert than corresponding soluble NPs catalysts.¹⁹ In view of the above, we wanted to explore the use of soluble NPs generated in situ for this process. PEG-400 is known to be an excellent dispersion agent and stabilizer for soluble metal NPs.^20,21 Abdul Rahman Mohamed et al. found that iron metal NPs formed in an ethanol-PEG-400 solution displayed a more uniform distribution.²² In this work, we introduce NaBH₄/NiCl₂·6H₂O in EtOH/PEG-400 to the reduction of alkenes, to the best of our knowledge, the system is novel for the reaction. The novel system was expected to show the following advantages (Scheme 1): (a) NaBH₄ not only reduces Ni²⁺ to soluble Ni (0) NPs in situ, but also serves as hydrogen donation for the reduction of alkenes with ethanol; (b) the in situ generated soluble Ni (0) NPs catalyst stabilized by PEG-400 is stable, efficient and recyclable for the reduction of alkenes.Open in a separate windowScheme 1Reduction of alkenes using NaBH₄–NiCl₂·6H₂O in EtOH/PEG-400 system.We first chose the reduction of styrene as model reaction (12,15,23,24 This is possibly because the hydrogen source for the reduction can be sufficiently derived from the B–H of NaBH₄ and the O–H of ethanol in our catalytic system (ideally 1 molar of NaBH₄ can reduce 4 molar of alkenes with ethanol), as recently reported by Bai et al. for the semihydrogenation of alkynes with NaBH₄ in methanol.²⁵ The activity of the in situ generated Ni (0) NPs catalyst in EtOH/PEG-400 (3/2 ratio) had also been compared with the commercial RANEY® nickel catalyst. The results revealed that the in situ generated Ni (0) NPs exhibited a higher activity for the reduction of styrene (entries 4, 20). Thus, we can conclude that the EtOH/PEG-400 using NiCl₂·6H₂O–NaBH₄ is a very simple and efficient system for the reduction of styrene.Optimization of reaction conditions for the reduction of styrene^a

Photocatalytic cascade reactions and dye degradation over CdS–metal–organic framework hybrids

Two bifunctional CdS–MOF composites have been designed and fabricated. The hybrids exhibited synergistic photocatalytic performance toward two cascade reactions under visible light integrating photooxidation activity of CdS and Lewis acids/bases of the MOF. The composite further promoted the photodegradation of dyes benefiting from effective electron transfer between the MOF and CdS.

Two bifunctional CdS–MOF composites have been successfully fabricated and exhibited synergistic photocatalytic performance toward two-step cascade reactions and dye photodegradation.

Cascade reactions are usually required for the synthesis of pharmaceuticals, pesticides and various fine chemicals,¹ especially for heterocyclic compounds.^1b Typically, benzylidene malononitrile, an essential intermediate for pharmaceutical production,^1f is normally prepared through a two-step reaction involving first oxidation of benzyl alcohol and then a Knoevenagel condensation of benzaldehyde with malononitrile.^2d Generally, the first step is mainly concentrated on the precious metal catalysts, and usually requires organic solvent, high temperatures, or high O₂ pressures, which largely limits its large-scale application.² The second Knoevenagel reaction is traditionally catalyzed by weak bases under homogeneous conditions, which is not favourable for recovery and recycling of catalysts.^2c Therefore, it is of great importance to develop a low-cost, stable and environmentally-friendly multifunctional catalyst.Solar energy, as an abundant natural resource, has attracted significant interest in photocatalytic water splitting, CO₂ or organic substrate transformations.^3,4 However, given that natural solar radiation is scattered, intermittent and constantly fluctuating, increasing the conversion rate of solar energy into chemical energy through photosensitive materials remains to be a great challenge.⁵ Significantly, a typical semiconductor material, CdS, displays excellent photocatalytic performance for many chemical reactions under light irradiation, such as photooxidation due to its a narrow band gap energy (2.4 eV) and efficient visible light absorption.⁶ However, the fact that a rapid recombination of photoelectrons and holes in CdS, and easy agglomeration of CdS nanoparticles (NPs) greatly impedes its practical application.^6d,7 Therefore, stable and effective supports should be required to stabilize pure CdS NPs.Metal organic frameworks (MOFs),⁸ featuring ordered porosities and large surface areas, have been widely used to stabilize various guest molecules, including metal nanoparticles, semiconductors and quantum dots.^7,8d,9 Recently, MOF-based composites have attracted intensive attention in photocatalysis field.^5a,9f,10 Unfortunately, most MOFs exhibit a wide bandgap and only absorb ultraviolet light region.^7,11 In addition, pure MOFs generally have a single active site, largely limiting catalytic reaction types.^9d Therefore, photoactive CdS combined with the advantages of MOFs can help construct a synergistic hybrid material.⁷Bearing above idea in mind, we have successfully fabricated a bifunctional CdS/NH₂-MIL-125 photocatalyst based on photosensitive CdS and active NH₂-MIL-125 (Scheme 1). The cooperative effect greatly improved photocatalytic performance of the composite toward the cascade reaction of selective oxidation of benzyl alcohol to benzaldehyde tandemly with a condensation of benzaldehyde with malononitrile. The superior catalytic activity mainly benefits from excellent photooxidation activity of CdS while the outer NH₂-MIL-125 plays multiple roles; it acts as a Lewis base site, accelerates the reaction by O₂ enrichment in air atmosphere, and stabilizes the CdS cores. Furthermore, effective electron transfer between MOF and CdS endows the hybrid outstanding photo-degradation performance toward organic pollutants.Open in a separate windowScheme 1Schematic illustration for the preparation of CdS/MOF hybrid.The crystallographic structure of CdS/NH₂-MIL-125 ^7c,d is analyzed and confirmed using powder X-ray diffraction (PXRD). As shown in Fig. 1a, the as-synthesized NH₂-MIL-125 has identical diffraction patterns as the simulated NH₂-MIL-125, which indicates the successful synthesis of MOF. For the diffraction patterns of CdS/NH₂-MIL-125, except for the typical diffraction peaks of MOF, two additional peaks appear at 2-theta values of 26.5° and 43.9° are assignable to CdS. And the peak intensities are enhanced along with increased CdS loadings. N₂ sorption experiments reveal that the Brunauer–Emmett–Teller (BET) surface areas of NH₂-MIL-125 and 15 wt% CdS/NH₂-MIL-125 are 956 and 613 m² g⁻¹, respectively (Fig. 1b). The decreased surface areas indicate that CdS NPs may be successfully loaded on the MOF, and are well stabilized by the pores. The morphology of 15 wt% CdS/NH₂-MIL-125 is investigated by scanning electron microscopy (SEM). Fig. 1c shows the retained octahedral morphology of MOF with an average diameter of 200–300 nm. In addition, the transmission electron microscopy (TEM) image shows uniform dispersion of CdS particles (average size, 3.7 nm) throughout MOF (Fig. 1d), further demonstrating their successful assembly. The actual contents of CdS in CdS/NH₂-MIL-125 samples have been confirmed by inductively coupled plasma atomic emission spectrometry (ICP-AES). The percentages by weight of CdS are very close to the nominal values (Table S1, ESI^†).Open in a separate windowFig. 1(a) PXRD patterns of simulated NH₂-MIL-125, as-synthesized NH₂-MIL-125, and CdS/NH₂-MIL-125. (b) N₂ sorption isotherms of NH₂-MIL-125 and 15 wt% CdS/NH₂-MIL-125 at 77 K. (c) SEM and (d) TEM images of 15 wt% CdS/NH₂-MIL-125 and (inset in d) the corresponding size distribution of CdS NPs.The cascade reaction between benzyl alcohol and malononitrile to produce benzylidene malononitrile under visible light irradiation has been investigated by CdS/NH₂-MIL-125. The reaction involves two steps including the first photocatalytic oxidation of benzyl alcohol to form benzaldehyde, and the second Knoevenagel reaction of benzaldehyde and malononitrile. As shown in †). These results highlight the important roles of each component in CdS/NH₂-MIL-125 and their excellent synergistic effects toward cascade reaction.Cascade reactions of benzyl alcohol oxidation followed by Knoevenagel condensation^a

Highly dispersed Ni nanoparticles on mesoporous silica nanospheres by melt infiltration for transfer hydrogenation of aryl ketones

Nickel-based catalysts have been applied to the catalytic reactions for transfer hydrogenation of carbonyl compounds. In the present work, highly dispersed nickel particles located at the pores of mesoporous silica spheres (Ni@mSiO₂) were prepared via an optimized melt infiltration route. The nickel nanoparticles of 10 wt% in the Ni@mSiO₂ catalyst could be uniformly loaded with high dispersion of 36.3%, resulting excellent performance for catalytic transfer hydrogenation of aryl ketones.

Nickel-based catalysts have been applied to the catalytic reactions for transfer hydrogenation of aryl ketones.

The reduction of carbonyl compounds has received steady interest as a common transformation in organic synthetic chemistry. Corresponding alcohols are important building blocks for the manufacture of chemicals, pharmaceuticals, and cosmetics.^1,2 The transfer hydrogenation (TH) reaction of ketones has lots of advantages owing to its low cost, simple process, easy handling, and mild conditions.³ Isopropyl alcohol both as a solvent and hydrogen donor provides safe reaction conditions.⁴ Until now, many catalysts have been developed for TH reactions.⁵Among the catalysts for TH reactions, nickel-based catalysts are representative, due to the metallic nickel surface can absorbs hydrogen and easily activates hydrogen in the atomic state.^6–11 In addition, nickel compounds could be the significant catalyst candidate because of the low price, accessibility, and high reactivity.^12,13 Therefore, several works used nickel nanocatalysts for TH reactions.^{14–17,44–51} However, developing the new supported catalyst with the high metal dispersion and narrow particle size distribution is still required, because it can enhance the reactant conversion and improve product yield.¹⁸ Recently, melt infiltration process has been exploited to prepare supported nanocatalysts as a fast and convenient route with no solvent use.^19–21The method which uses highly porous supports with regular porosity and hydrated metal salts with mild melting temperatures, allowed the metal salts to permeate inside the porous support via capillary forces. High performance nanocatalysts based on well-dispersed nanoparticles could be obtained through uniform infiltration of metal precursors and sequential thermal treatment.²² The obtained nanoparticles have narrow size distributions as well as small sizes, enlarging active sites.^23,24Mesoporous silica nanosphere (mSiO₂) as a porous support can be an outstanding platform for the synthesis of metal nanoparticle, owing to the good thermal stability, high surface area, and large pore volume as well as uniform pore structures.^25–29 Herein, we report a new catalyst with highly dispersed Ni nanoparticles at mesoporous silica sphere nanostructures (Ni@mSiO₂) for catalytic TH reactions, which was synthesized through a melt infiltration of hydrated nickel salts and a sequential thermal reduction (Scheme 1). First, mSiO₂ supports could be prepared by a sol–gel method based on a modified Stöber process. More details were described in the ESI.^† The mesopores were formed in the silica nanospheres using the cationic surfactant C₁₆TAB as a self-assembly template. The TEM images show mesoporous silica spheres with an average diameter of 417 ± 20 nm (Fig. 1a and b). Ordered mesoporous channels were generated by removing the long carbon chains of C₁₆TAB by calcination at 500 °C. The corresponding Fourier-transform (FT) pattern showed a ring pattern of polycrystalline (inset of Fig. 1c). The inverse fast Fourier-transform (IFFT) image, calculated by Micrograph TM Gatan software, also demonstrated the existence of hexagonal lattice planes (Fig. 1c).Open in a separate windowScheme 1A brief synthetic scheme of Ni@mSiO₂ nanocatalyst.Open in a separate windowFig. 1(a and b) TEM images, (c) FT pattern for (b) (inset of c) and IFFT image, (d) HRTEM image, (e) N₂ adsorption/desorption isotherms, and (f) pore size distribution diagrams of mSiO₂. The bars represent 1 mm (a), 100 nm (b), and 20 nm (d).The brightest of the rings originated from a two-dimensional hexagonal (p6mm) structure with d100 spacing. The interplanar spacing computed from the brightest FFT diffraction ring was approximately 3 nm, corresponding to the pore sizes shown in the TEM image (Fig. 1d).N₂ sorption experiments for the mSiO₂ nanosphere exhibited type IV adsorption–desorption hysteresis with H4 type hysteresis loop (Fig. 1e). The Brunauer–Emmett–Teller (BET) surface area and pore volume of the mSiO₂ nanosphere were 1501 m² g⁻¹ and 0.70 cm³ g⁻¹, respectively. The average pore size was estimated to be approximately 2 nm from the adsorption/desorption branches of N₂ isotherms by using the Barrett–Joyner-Halenda (BJH) method (Fig. 1f). Scheme 1 illustrated the simple procedure for the synthesis of the Ni@mSiO₂ nanocatalyst. Based on the small pore size (3 nm) of mSiO₂ nanospheres, very tiny nickel nanoparticles (∼2 nm) could be generated via a melt-infiltration process and thermal treatment under hydrogen flow. Using a 0.55 g_{nickel salt}/g_silica support ratio, the hydrated nickel salt (melting point = 56.7 °C) was successfully incorporated in the mSiO₂ nanosphere during the melt infiltration process, driven by the capillary forces. The Ni-loading content after the final thermal treatment was calculated to be nominally 10 wt% on the basis of Ni converted from the nickel nitrate salt. First, the hydrated nickel salt was melt-infiltrated into the mesoporous silica pores of the mSiO₂ nanospheres by physical mixing at room temperature with subsequent aging at 60 °C for 24 h in a tumbling oven. Then, tiny nickel nanoparticles were generated by thermal reduction of the confined hydrated Ni salt in the small pores at 500 °C under hydrogen flow.The low-resolution TEM images of the Ni@mSiO₂ nanostructure show Ni nanoparticles as black dots (Fig. 2a and b). The high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) image showed bright dots of a very small size (average 2.0 nm), which indicates uniform incorporation of the Ni nanoparticles in the porous silica (Fig. 2c and S1 in the ESI^†). In the elemental mapping of silica (green color) and nickel (red color), high dispersion of nickel nanoparticles was observed (Fig. 2d). HRTEM analysis showed lattices of a single Ni nanoparticles in the mSiO₂ pores (Fig. 2e). The inner particle size was observed to be around 2 nm. The Fourier-transform pattern represented a single crystal of metallic nickel with a distance of 0.2 nm between neighboring fringes, which corresponded to the (111) planes of face centered-cubic nickel (Fig. 2e).Open in a separate windowFig. 2(a and b) TEM and (c) HAADF TEM images, (d) scanning TEM image with elemental mapping and (e) HRTEM images, and (f) XRD spectrum of Ni@mSiO₂ nanostructure. The bars represent 200 nm (a), 20 nm (b–d), and 2 nm (e).The X-ray diffraction (XRD) spectrum of Ni@mSiO₂ nanocatalyst has a broad peak at 2θ = 44.5°, which is assigned to the reflections of the (111) plane in the fcc-nickel phase (Fig. 2f, JCPDS No. 04-0850). The average crystal size of the nickel particle was estimated to be 1.8 nm, from the broadness of the (111) peak using the Debye–Scherrer equation, which is well-matched with that observed in the TEM images. The other intense peak around 23° of the Ni@mSiO₂ nanocatalyst indicates the presence of amorphous silica.Using a H₂ chemisorption experiment, the active nickel surface area and average nickel particle size of the Ni@mSiO₂ nanocatalyst could be analyzed, and measured 242 m² g⁻¹ and 2.78 nm, respectively. The obtained Ni dispersion was very high, and was calculated to be 36.3%.The XPS spectrum analysis was carried out to probe the chemical states of Ni@mSiO₂ (Fig. S2^†). The Ni 2p peak of Ni@mSiO₂ showed NiO and Ni peak. The four peaks at 853.9, 855.6, 860.7, and 863.5 eV are assigned to NiO, and the other peak at 852.1 eV is assigned metallic Ni peak. The metallic Ni surface of the small nanoparticles (∼2 nm) was easily oxidized under an ambient condition.N₂ sorption experiments for the Ni@mSiO₂ nanocatalyst showed a type IV isotherm with type H4 hysteresis (Fig. 3a). The BET surface area was calculated to be 636 m² g⁻¹. The total pore volume was found to be 0.3 cm³ g⁻¹, which is about 43% of the initial mSiO₂ nanosphere (0.7 cm³ g⁻¹). The significant decrease in pore volume was attributed to inner nickel nanoparticle occupancy. Applying the BJH method, small pore sizes were obtained by the adsorption/desorption branches (Fig. 3b). Because of the occupancy of tiny nickel particles in the pristine silica pores, the pore size of the Ni@mSiO₂ nanocatalyst was also slightly decreased, and was observed to be 1.8 nm.Open in a separate windowFig. 3(a) N₂ adsorption/desorption isotherms and (b) pore size distribution diagrams of Ni@mSiO₂ nanocatalyst.The Ni@mSiO₂ nanocatalyst was applied to the hydrogen-transfer reaction of acetophenone. Acetophenone is an ideal substrate in the hydrogen transfer reaction, and is generally used as a hydrogen acceptor.³⁰ Among the various products of acetophenone reduction, only 1-phenylethanol resulted from the catalyzed reaction. The metallic Ni on the catalyst surface is the active species and the reaction was promoted by base.¹⁷ The dihydride species referred in this catalyst system to make alcohol from the transfer of the two hydrogen atoms of the donor to the surface of the metal.³¹ However, small amount of various byproduct including hemiacetals and condensation products which is occurred between ketone and alcohol were produced due to basic conditions.³² For optimization, the reaction parameters, such as amount of catalyst and base, temperature, and time, are adjusted. The TH reaction results of acetophenone are summarized in EntryCat. (mol%)Temp. (°C)Time (min)Base (eq.)Conv.^b (%)Yield^b (%)TON1111045110095952111060176737331100602100999941100601100929251100600.562595961906011009696718045158555581806017268689180751100979710180901676565110.58075110096192120.25807511095380130.1807516260603140.05100602806262Open in a separate window^aRxn. condition: acetophenone (2 mmol), i-PrOH (solvent, 10 mL), base (NaOH).^bDetermined by GC-MS spectroscopy.^cnickel-aluminium alloy purchased from Lancaster (10034177) was applied.First, we studied the effect of the base and determined the amount of base required (Entries 3–6, 33,34 Although no reaction was observed without bases, a small amount of base was sufficient to trigger the reaction (Entry 5, 6,15,35 The optimized conditions were applied to extend the scope.To verify the general applicability of Ni@mSiO₂, various aromatic ketones were tested (†).^36–43Catalytic transfer hydrogenation reactions of various aromatic carbonyl compounds with Ni@mSiO₂^a

Synthesis of CHF2-substituted 3-azabicyclo[3.1.0]hexanes by photochemical decomposition of CHF2-pyrazolines

A practical synthesis of CHF₂-substituted 3-azabicyclo[3.1.0]hexanes was developed for the first time. The key step was photochemical decomposition of CHF₂-substituted pyrazolines. This protocol has the advantages of simple operation, and mild conditions, as well as excellent functional group tolerance, giving the desired products in moderate to excellent yields.

A general and efficient method has been developed to synthesize CHF₂-substituted 3-azabicyclo[3.1.0]hexane derivatives via photochemical decomposition of CHF₂-pyrazolines.

The 3-azabicyclo[3.1.0]hexyl ring system as a conformationally constrained bicyclic isostere for the piperidine motif displays diverse biological activities and great potential in the pharmaceutical industry.¹ Representative examples of this type of application are potent μ opioid receptor antagonist 1 for the treatment of pruritus,² the ketohexokinase (KHK) inhibitor 2 for the treatment of non-alcoholic fatty liver disease (NAFLD),³ muscarinic receptor antagonist 3 (ref. 4) and T-type calcium channel inhibitor 4 (ref. 5) (Fig. 1). In this context, considerable effort has been devoted to developing general and efficient methods for the synthesis of the 3-azabicyclo[3.1.0]hexane scaffolds (Scheme 1). The elegant early studies focused on the intramolecular cyclopropanation, such as metal-catalyzed oxidative cyclization of 1,6-enynes⁶ and cyclopropanation of N-allylamino acid dimethylamides using Ti(ii) reagents.⁷ Furthermore, the intermolecular cyclization of 3-pyrrolines and metal carbenoids was also a useful tool to construct this core structure.⁸ Although these known procedures had their merits, they were also associated with some drawbacks. For example, requiring long routes for the starting materials preparation and/or using expensive metal catalytic systems. In the last few years, [3 + 2] cycloaddition process has been the most popular method to construct this cyclopropane ring of 3-azabicyclo[3.1.0]hexanes. The coupling of maleimides and hydrazines has been reported by Lunn''s group.⁹ And Jiang and co-workers have disclosed a method of palladium-catalyzed cyclopropanation of maleimides and N-tosylhydrazones.¹⁰ To match the increasing scientific and practical demands, it is still of continued interest and great importance to explore new and straightforward methods to access these highly rigid cyclopropanes with more simple operation.Open in a separate windowFig. 1Representative bioactive compounds with a 3-azabicyclo[3.1.0]hexane core structure.Open in a separate windowScheme 1Construction of 3-azabicyclo[3.1.0]hexane scaffolds.On the other hand, decoration of organic molecules with fluorinated groups often affects their physicochemical and biological properties such as metabolic stability and lipophilicity,¹¹ so organofluorine compounds are widespread in pharmaceuticals, agrochemicals, and advanced functional materials. Among all fluorine-containing groups, difluoromethyl group can develop special effects on molecules: it can be used as a bioisostere of a carbinol moiety and as a more lipophilic hydrogen bond donor.¹² However, protocols for the synthesis of difluoromethylated azabicyclo[3.1.0]hexanes remain to be underexplored. In line with previous work from our group dealing with the preparation of difluoromethyl-substituted pyrazolines using in situ generated difluoromethyl diazomethane,¹³ we report herein the development of a simple and efficient method to synthesize CHF₂-substituted 3-azabicyclo[3.1.0]hexane derivatives from commercially available maleimides.Following our previously established protocol,¹⁴ we initially examined the thermal decomposition of pyrazoline A′, and the desired 3′a was observed in 51% yield, but 3′a was obtained only in 27% yield based on 1-benzyl-1H-pyrrole-2,5-dione 2a (see Scheme S1 and S2^†). Considering the low yield and the tedious operation, we tried to develop a one-pot cascade approach (see Table S1^†). Accidentally, we discovered that photochemical process was more effective than thermal decomposition. As we all know, photochemistry is considered as one of the simplest manifolds of chemical reactivity and photochemical reactions are the key for the synthesis of many reactive intermediates.¹⁵ Accordingly, this phenomenon attracted our attention. On the other hand, considering the quantitative formation of the isomeric Δ²-pyrazoline B′ in the [3 + 2] cycloaddition process, we decided to prevent the formation of the byproduct B′ by taking the simplest higher homologue – CF₂H(CH₃)CNH₂ (Scheme 2).Open in a separate windowScheme 2Synthesis of 3-benzyl-6-difluoromethyl-3-azabicyclo[3.1.0]hexane-2,4-dione.Initial tests were done on CF₂H(CH₃)CHN₂I generated in situ and 1-benzyl-1H-pyrrole-2,5-dione 2a as the model substrates.¹⁶ To our delight, both trans (3a₁) and cis (3a₂) products were isolated separately and the yields of 3a₁ and 3a₂ were 39% and 12%, respectively (†), and an example of which was shown for 3a₁ in Fig. 2. The bridgehead protons were correlated through space to the nearby difluromethyl protons, indicating they were on the same convex side of the bicyclic system. Encouraged by this result, we further optimized the reaction conditions, and the results were showed in Entry1 (equiv.) t-BuONO (equiv.)AcOH (equiv.)SolventLamp power (W)Time (h)Yield^b (%)dr^c3a₁3a₂12.02.40.4Toluene50024391278 : 2223.03.60.6Toluene50024511478 : 2234.04.80.8Toluene50024441476 : 2443.03.60.6THF50024291369 : 3153.03.60.6DMSO50024n.d.n.d.—63.03.60.6Et₂O50024521479 : 2173.03.60.6(i-Pr)₂O50024361275 : 2583.03.60.6i-PrOMe50024511478 : 2293.03.60.6MeCN50024561480 : 20103.03.60.6MeCN40024501676 : 24113.03.60.6MeCN60024581579 : 21123.03.60.6MeCN80024611679 : 21133.03.60.6MeCN1000^d24641680 : 20143.03.60.6MeCN100020631680 : 20153.03.60.6MeCN100028661680 : 20163.03.60.6MeCN100032641779 : 21Open in a separate window^aReaction conditions: a solution of 1-methyl-2,2-difluoroethanamine 1 in CHCl₃ and t-BuONO and HOAc were added in turn. After 10 min heating, the obtained yellow solution was cooled down to a room temperature by external water bath. Then 2a was added into the reaction mixture and stirred at 45 °C. After removing CHCl₃, the residue was dissolved in 5 mL solvent and transferred into a quartz tube which was irradiated with a high-pressure mercury lamp (250–720 nm).^bIsolated yield by chromatography on silicagel.^cDiastereomeric ratio of 3a₁ and 3a₂ was based on column chromatography.^dThis is the maximum power of this lamp.Open in a separate windowFig. 2NOESY of 3a₁ (irradiate hydrogen nuclei of 6-difluoromethyl).With the optimized reaction conditions in hand, the generality of maleimides in this cyclopropanation reaction was examined, and the results were summarized in Open in a separate window^aReaction conditions: a solution of 1-methyl-2,2-difluoroethanamine 1 (0.1 M, 3.0 eq.) in CHCl₃ and t-BuONO (3.6 eq.) and HOAc (0.6 eq.) were added in turn. After 10 min heating, the obtained yellow solution was cooled down to a room temperature by external water bath, and 2 (1.0 eq.) was added immediately. The reaction mixture was stirred at 45 °C for 12 h. After removing CHCl₃, the residue was dissolved by acetonitrile (5 mL) and transferred into a quartz tube which was irradiated with a 1000 W high-pressure mercury lamp for 28 h.^bIsolated yield.^cDiastereomeric ratio of trans and cis products was based on column chromatography.^dIsolated yield combined trans and cis products.^eDiastereomeric ratio was based on ¹H NMR.We further explored its application for the synthesis of the 3-azabicyclo[3.1.0]hexane scaffold. To our satisfaction, the representative reduction of the carbonyl groups in 3a₁ with LiAlH₄ in diethyl ether smoothly gave the pyrrolidine 4a₁ in nearly quantitative yield (Scheme 3).¹⁴ It is worth mentioning that no cyclopropane ring cleavage was observed during this reaction.Open in a separate windowScheme 3Synthesis of 3-azabicyclo[3.1.0]hexane 4a₁.Based on the experimental results and the previous literature,¹⁷ a plausible mechanistic pathway is depicted in Scheme 4 with 2a as a model substrate. Mechanistically, [3 + 2] cycloaddition is carried out with CF₂H(CH₃)CHN₂ and 2a to generate pyrazoline A. Subsequently the photodenitrogenation of pyrazoline occurs by the stepwise cleavage of the two C–N N–C bonds to give a 1,3-biradical. Finally, the 1,3-biradical recombines to give cyclopropane diastereoisomers 3a₁ and 3a₂.Open in a separate windowScheme 4Proposed mechanism.In summary, we have developed a general and efficient method for the synthesis of CHF₂-substituted 3-azabicyclo[3.1.0]hexane derivatives via photochemical process of commercially available maleimides and in situ generated CF₂H(CH₃)CHN₂. It is worth mentioning that both of the diastereoisomers could be easily isolated by silica gel chromatography. This protocol has the advantages of simple operation, mild conditions as well as excellent functional group tolerance. We believe that this method will expand the synthetic arsenal in the field of medicinal chemistry, agrochemistry and organic synthesis.     

Enantioselective conjugate hydrosilylation of α,β-unsaturated ketones

Enantioselective conjugate hydrosilylation of β,β-disubstituted α,β-unsaturated ketones was realized. In the presence of a chiral picolinamide–sulfonate Lewis base catalyst, the reactions provided various chiral ketones bearing a chiral center at the β-position in up to quantitative yields with moderate enantioselectivities.

Enantioselective conjugate hydrosilylation of β,β-disubstituted α,β-unsaturated ketones was realized.

Chiral ketones are important intermediates for the synthesis of natural products or chiral drugs, and some themselves are useful chiral drugs.¹ Asymmetric conjugate reduction of α,β-unsaturated carbonyl compounds is an attractive and challenging transformation for the construction of chiral ketones. During the past few decades, many groups have devoted considerable efforts to this area and made great improvement, for instance, transition metal catalyzed asymmetric hydrogenation of α,β-unsaturated carbonyl compounds, including palladium,² iridium,³ copper,⁴ ruthenium,⁵ rhodium⁶ and cobalt.⁷ Besides, some organocatalyzed asymmetric conjugate transfer hydrogenations using Hantzsch ester⁸ or pinacolborane⁹ as the hydride source have also been reported. However, very few examples about chiral Lewis base catalyzed conjugate hydrosilylation of α,β-unsaturated carbonyl compounds have been reported and only chiral phosphine oxide Lewis base catalysts were used in these reactions (Scheme 1).¹⁰ Therefore, exploration of the application of other kinds of chiral Lewis base catalysts in this reaction is still highly desirable.Open in a separate windowScheme 1Enantioselective conjugate hydrosilylation of α,β-unsaturated ketones by chiral Lewis base catalysts.Recently, we developed a kind of easily accessible chiral picolinamide–sulfonate Lewis base catalysts and used them in asymmetric hydrosilylation of α-acyloxy-β-enamino esters,¹¹ one of them exhibiting excellent reactivity, diastereoselectivity and enantioselectivity. Herein we present the enantioselective conjugate hydrosilylation of β,β-disubstituted α,β-unsaturated ketones using this kind of Lewis base as catalysts, leading to various chiral ketones bearing a chiral center at β-position (Fig. 1).Open in a separate windowFig. 1Three typical chiral drugs containing chiral ketone moiety.First, various chiral Lewis base catalysts 2 were screened in the enantioselective hydrosilylation of (E)-1,3-diphenylbut-2-en-1-one 1a in acetonitrile at 0 °C. As shown in Fig. 2, l-piperazine-2-carboxylic acid derived N-formamide 2a,^12aR-(+)-tert-butylsulfinamide derived catalyst 2b^12b and picolinamide 2c^12c were found to be totally inactive for the reaction. Meanwhile picolinamide–tosylate catalyst 2d was highly active to afford the product with excellent yield in moderate ee value. Afterwards, several picolinamide–tosylate catalysts 2f–2h bearing electron-withdrawing group in 4-position of pyridine were employed in the reaction and 4-bromo picolinamide 2f delivered a slightly higher ee value. 5-Methoxy picolinamide 2i gave the product with the same ee value as that of 2d but in much lower yield. Lower enantioselectivities were observed with 4-phenyl picolinamide 2j and 3-methyl picolinamide 2k. When (R)-1-(2-aminonaphthalen-1-yl)naphthalen-2-ol derived catalyst 2l was used, no product was observed. When (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol derived catalyst 2m gave the product in both poor yield and ee value. Moreover, two picolinamide–sulfonamide catalysts 2n and 2o were also used in the reaction and almost racemic products were obtained. Hence, 2f was determined as the optimal catalyst and was used through out our study.Open in a separate windowFig. 2Evaluation of the chiral Lewis base catalysts 2 in conjugate hydrosilylation of (E)-1,3-diphenylbut-2-en-1-one 1a. Unless otherwise specified, the reactions were carried out with 1a (0.1 mmol), trichlorosilane (0.2 mmol) and catalyst 2 (0.02 mmol) in 1 mL of acetonitrile at 0 °C for 24 hours. Isolated yield based on 1a. The ee values were determined by using chiral HPLC.Subsequently, the other reaction conditions were optimized. The results are summarized in Entry^aSolvent T (°C)Time [h]Yield^b [%]ee^c,d [%]1CH₃CN0247751 (R)2CH₃CH₂CN0248450 (R)3C₆H₅CN0248324 (R)4THF0249211 (R)51,4-Dioxane024635 (R)6CHCl₃0249225 (S)7CH₂Cl₂0249638ClCH₂CH₂Cl0249010 (R)9CCl₄0249535 (S)10Toluene0249555 (S)11Xylene024N.R.—12Mesitylene024N.R.—13C₆H₅CF₃0249531 (S)14Toluene−10489764 (S)15Toluene−20609265 (S)16Toluene−4072N.R.—Open in a separate window^aUnless otherwise specified, the reactions were carried out with 1a (0.1 mmol), trichlorosilane (0.2 mmol) and catalyst 2f (0.02 mmol) in 1 mL of solvent.^bIsolated yield based on 1a.^cThe ee values were determined by using chiral HPLC.^dThe absolute configuration of 3a was determined by comparison of the retention times of the two enantiomers on the stationary phase with those in the literatures.With the optimized conditions in hand, the scope and limitations of the reaction were explored. The results are summarized in Fig. 3. In the presence of 20 mol% of chiral Lewis base catalyst 2f and 2 equivalents of trichlorosilane, various α,β-unsaturated ketones were hydrosilylated. We first tested the effect of various 3-aryl groups of 1. 3-(4-Methoxy-phenyl) substrate 3e (Fig. 3) and 3-(naphthalen-2-yl) substrate 3i (Fig. 3) underwent the reaction to give the products with good yields in enantioselectivities close to 3a, while lower ee values were observed with 3b–3d, 3h, 3k and 3l (Fig. 3). No product was obtained with 3-(2-chloro-phenyl) substrate 3f and 3-(naphthalen-1-yl) substrate 3j, perhaps due to the high steric hindrance (Fig. 3). When 3-(2-methoxy-phenyl) substrate 3g was used, by prolonging the reaction time to 60 hours, the product was obtained with good yield but very poor enantioselection (Fig. 3). Trace amount of the product was detected with 3-(pyridin-2-yl) substrate 3m (Fig. 3). Next, some 3-phenyl-but-2-en-1-ones with different 1-aryl groups were also employed in the reaction. The 4-substituted or 3-substituted substrates delivered good yields of the products with similar or slightly lower enantioselectivities (Fig. 3), while much lower ee value was observed with 2-substituted substrate 3s (Fig. 3). For some other 3-alkyl chalcones, moderate to good yields and moderate ee values were obtained (Fig. 3), except for the bulkier tertiary butyl substituted 3w that gave trace amount of the product (Fig. 3). Reaction of 3y with two different 3,3-aryl groups afforded the product with moderate yield in very low enantioselectivity (Fig. 3). Finally, cyclic substrate 3z was subjected in the reaction and provided the product with excellent yield but in poor ee value (Fig. 3).Open in a separate windowFig. 3Substrate scope of the reaction. Unless otherwise specified, the reactions were carried out with 1 (0.1 mmol), trichlorosilane (0.2 mmol) and catalyst 2f (0.02 mmol) in 1 mL of toluene at −10 °C for 48 hours. Isolated yield based on 1. The ee values were determined by using chiral HPLC. The absolute configuration of 3a was determined by comparison of the retention times of the two enantiomers on the stationary phase with the literatures. The absolute configurations of other products were determined in analogy. ^aThe reaction time was 60 hours. ^bThe reaction time was 72 hours.Although detailed structural and mechanistic studies remain to be carried out, based on the absolute configuration of the product 3a, we propose a mechanism shown in Scheme 2. First, the nitrogen atom of the pyridine ring and the carbonyl oxygen atom of catalyst 2f are coordinated to Cl₃SiH to create an activated hydrosilylation species. Substrate 1a may approache the Cl₃SiH-catalyst complex to generate two transition states A and B. In transition state A, the N–H of catalyst 2f activates the carbonyl group of 1a through H-bonding. In addition, there could be π–π stackings between the two aromatic systems of the catalyst and the substrate. Then Si-face conjugate attack of the hydride to 1a generate (S)-product 3a. On the contrary, in transition state B through which (R)-product will be obtained, the carbonyl group of 1a can not be connected with the N–H of catalyst 2f. Thus the fact that (S)-enriched product 3a was obtained is consistent with the suggestion that the hydrosilylation predominantly proceeds through the pathway involving transition state A rather than transition state B.Open in a separate windowScheme 2A plausible reaction mechanism for hydrosilylation of 1a catalyzed by 2f.In conclusion, we have developed a facile, metal-free and mild enantioselective conjugate hydrosilylation of β,β-disubstituted α,β-unsaturated ketones. By using chiral picolinamide–sulfonate Lewis base as catalyst, the reactions provided various optically active ketones bearing a chiral center at β-position with moderate to good yields in moderate enantioselectivities. Comparing with the chiral phosphine oxide Lewis base catalysts, the chiral picolinamide–sulfonate is cheaper and easier accessible. The absolute configuration of one product was determined by comparison of the retention times of the two enantiomers on the stationary phase with those in the literature.     

Sc3N@Ih-C80 based donor–acceptor conjugate: role of thiophene spacer in promoting ultrafast excited state charge separation

Light induced charge separation in a newly synthesized triphenylamine–thiophene-Sc₃N@I_h-C₈₀ donor–acceptor conjugate and its C₆₀ analog, triphenylamine–thiophene-C₆₀ conjugate is reported, and the significance of the thiophene spacer in promoting electron transfer events is unraveled.

Photoinduced charge separation and dark charge recombination occurring within picoseconds is observed in newly synthesized triphenylamine–thiophene-Sc₃N@I_h-C₈₀ and triphenylamine–thiophene-C₆₀ conjugates.

Endohedral metallofullerenes (EMF) are compounds of great interest due to their fascinating structure and unique electronic properties^1–4 which are different from those of empty fullerenes.^5,6 While the early efforts were dedicated to their electronic structure, their chemical functionalization has aroused significant interest in recent years,^7–9 not only to utilize their interesting properties but also to prepare new compounds with potential applications in photovoltaics,^10,11 biomedical^12–15 and materials science applications.^16,17 Due to their higher lowest unoccupied molecular orbital (LUMO) compared to those of empty fullerene cages, EMFs are excellent acceptor materials in organic photovoltaics, capable of increasing the open circuit voltage of the devices.¹⁰ To this end, a few covalent donor–acceptor systems comprising EMFs have been prepared,^8,18–20 which showed the higher stability of the radical-ion pair in comparison with analogous empty fullerenes.^21–31Up until now, several methods have been developed to functionalize EMFs such as Diels–Alder,^7,32,33 Bingel–Hirsch reaction,^34–37 cycloaddition with carbenes or benzynes etc.^38–41 Among these, 1,3-dipolar cycloaddition of azomethine ylides is perhaps the most used to functionalize EMFs,^38–42 although other dipoles as nitrile imines⁴³ have been used as well. On the other hand, nitrile oxides react with alkenes to afford 2-isoxazolines and can be prepared from aldoximes by treatment with a chlorinated agent and a weak base, generally (except for hindered nitrile oxides) prepared in situ to circumvent dimerization.⁴⁴ Cycloadditions of nitrile oxides on fullerenes,⁴⁵ carbon nanotubes^46,47 or graphene⁴⁸ are known but only one example of the cycloaddition of a stable nitrile oxide to Sc₃N@I_h-C₈₀ has been described⁴⁹ in an elegant study showing that the isoxazoline ring is fused to a [5,6]-bond junction in the endohedral cage.Here, we describe the synthesis and photophysical study employing femtosecond transient absorption (fs-TA) spectroscopy, of a donor–acceptor conjugate formed by a triphenylamine moiety as a donor group and Sc₃N@I_h-isoxazoline-C₈₀ as the acceptor, linked by a thiophene spacer (Fig. 1). The analogous C₆₀ derivative was also prepared for comparison. Here we show that the central thiophene ring promotes π-conjugation between the donor and acceptor entities thus facilitating charge separation processes in these conjugates, useful for optoelectronic applications.Open in a separate windowFig. 1Structure of the newly synthesized triphenylamine–thiophene-Sc₃N@I_h-C₈₀ endohedral fullerene conjugate, (3a) and its C₆₀ analog derivative (3b). Scheme 1 shows the synthetic approach for both donor–acceptor conjugates. Reaction of aldehyde 1⁵⁰ with hydroxylamine hydrochloride in ethanol/pyridine afforded oxime 2, as a mixture of Z–E isomers, in 77% yield. Then, 2 was reacted with N-chlorosuccinimide (NCS) and after 30 min a solution of Sc₃N@I_h-C₈₀ in 1,2-dichlorobenzene (o-DCB) and triethylamine was added and stirred for 72 h at room temperature. The progress of the reaction was followed by HPLC, which showed that a new single peak appears as that for Sc₃N@I_h-C₈₀ disappears. After purification by column chromatography, followed by preparative HPLC, conjugate 3a was obtained in 25% yield. A similar procedure was followed to prepare the C₆₀-based compound 3b (see the Experimental section in the ESI for details^†). Compound 3a was characterized by means of MALDI-TOF mass analysis showing the molecular ion peak at 1677.28 amu. The ¹H NMR spectrum contains all the expected signals of the addend. The thiophene H-atoms appear at 7.96 and 7.24 ppm, deshielded compared to those in the oxime due to the presence of the fullerene cage. Note that this signal is broad as a consequence of the hindered rotation. In the ¹³C NMR spectrum, the most relevant signals are those of the sp³ C-atoms of the functionalized fullerene cage at 97.7 and 70.3 ppm. Similar features are observed in the spectrum of the C₆₀-based compound 3b. Finally, the appearance of a broad UV-Vis absorption around 700 nm and the lack of absorption in the 800 nm region, expected for the [6,6]-isomer, confirmed the formation of the [5,6]-isomer; a result that agrees well with the previously described examples of 1,3-dipolar cycloadditions on Sc₃N@I_h-C₈₀.⁴⁹ Interestingly, 3a undergoes a fast retrocycloaddition when refluxed in o-DCB while 3b is stable under these conditions.Open in a separate windowScheme 1Reagents and conditions: (a) hydroxylamine hydrochloride, pyridine; (b) NCS; pyridine (c) Et₃N, Sc₃N@I_h-C₈₀ or C₆₀, r.t.The absorption spectrum of 3a and 3b in dichloromethane together with the parent oxime 2 are shown in Fig. 2a. Oxime 2 exhibits a maximum at 390 nm which is red-shifted to 412 nm and 407 nm in cycloadducts 3a and 3b, respectively, indicating a stronger influence of the Sc₃N@I_h-C₈₀ cage when compared to C₆₀ over the electronic properties of the organic addend. In the case of 3a, a band around 690 nm is observed and the spectrum lacked the typical band around 800 nm ascribed to [6,6]-EMF adducts;⁵¹ again confirming the [5,6]-structure for 3a, as discussed above.Open in a separate windowFig. 2(a) Absorption and (b) fluorescence spectra of 10⁻⁶ M solutions of 2 (red), 3a (black) and 3b (blue) in CH₂Cl₂.The photophysical properties of 3a and 3b were first studied in dichloromethane by steady-state fluorescence spectroscopy with a 407 nm excitation wavelength (λ_ex), which mostly excites the TPA moiety. The model oxime 2 showed strong fluorescence with a maximum at 544 nm. The fluorescence of this chromophore was fully quenched upon connection to the fullerene cages for both 3a and 3b (Fig. 2b). It is possible that photoinduced charge separation is the reason for the observed fluorescence quenching (vide infra).The electrochemical properties of 3a and 3b, oxime 2 and pristine Sc₃N@I_h-C₈₀ and C₆₀ were investigated by cyclic voltammetry (CV) and Osteryoung square wave voltammetry (OSWV) and the results are summarized in Fig. 3a. In the anodic region, the first oxidation potentials of 3a and 3b, attributed to the alkoxy-TPA-thiophenyl moiety, are positively shifted by 80 mV and 110 mV, respectively, compared to that for oxime 2 (isostructural with the organic addend of 3a–b), suggesting the existence of some electronic interactions with the respective fullerene cage. In the cathodic region, the first reduction potential of 3a is positively shifted by 270 mV when compared to that of pristine Sc₃N@I_h-C₈₀. This behavior is similar to what was previously observed for an isoxazoline Sc₃N@I_h-C₈₀ derivative, confirming the strong influence that functionalization has on the electrochemical properties of the EMF cage.⁵² However, the first reduction of 3b and C₆₀ showed similar values (−1.05 V and −1.03 V, respectively) as described in other donor-isoxazolinofullerene derivatives.⁴⁴ This behavior is different from that for C₆₀ derived pyrrolidinofullerenes, where the first reduction is about 120 mV more negative than for pristine C₆₀ as a result of the saturation of one of the double bonds.Redox potentials (in V vs. Fc/Fc⁺) determined by OSWV of the processes observed for 2, 3a–b and reference fullerenes^a

Electrocatalytic carboxylation of halogenated compounds with mesoporous silver electrode materials

Mesoporous silver materials are used as electrocatalysts for halogenated compounds. The mesoporous silver materials have uniform mesoporous size (8 nm), large specific surface area (12 m² g⁻¹), high pore volume (0.07 cm³ g⁻¹), and a good 3D network structure of the metallic silver skeleton. The results show that the prepared materials exhibit high performance in electrocatalytic carboxylation of halogenated compounds to acid (78%).

Mesoporous silver materials are used as electrocatalysts for halogenated compounds and exhibit high performance in electrocatalytic carboxylation of halogenated compounds to carboxylic acid (78%).

The main factor of global warming and the greenhouse effect is the increase of concentration of carbon dioxide (CO₂).^1,2 There are two ways to solve the problem of CO₂ concentration. The first method is to establish a low-carbon economic development model. The second method is to convert CO₂ into useful organic chemicals.^3,4 As human production and life are inseparable from the use of fossil fuels, the problem of CO₂ emissions will still exist. Therefore, today''s society urgently pays attention to how to effectively transform and utilize CO₂; in addition, the conversion of CO₂ into productive products has attracted widespread attention.^5,6 CO₂ conversion is a challenge because of its high chemical and thermodynamic stability. Through electrochemical means, CO₂ can be activated at normal temperature and pressure.⁷ Therefore, from the perspective of environmental protection and technical means, electrocarboxylation is a simple and easy method for CO₂ immobilization. Electrocatalytic carboxylation can be applied to a variety of substrates, such as olefins,⁸ alkynes,⁹ alcohols,¹⁰ aldehydes,¹¹ ketones,¹² epoxides,¹³ imines¹⁴ and organic halides.¹⁵ Halogenated compounds are toxic, carcinogenic and difficult to biodegrade. Electrocarboxylation of halogenated compounds not only immobilizes CO₂ and reduces environmental pollution, but also converts them into useful compounds. More importantly, several of them are fine chemicals with industrial use, and some of them can produce anti-influenza drugs, such as benzoic acid, sodium benzoate, benzyl benzoate etc.¹⁶Silver shows remarkable electrocatalytic activity when it is used for electrocarboxylation of organic halides.¹⁷ In addition, silver nanoparticles have been used in electrocatalytic reactions. In the field of electrocatalysis using silver nanoparticles, researchers have made great efforts. Firstly, a silver nanoparticle-modified electrode was successfully prepared and applied to electrocatalytic reduction of benzyl chloride.¹⁸ At the same time, through the electrochemical detection method, the catalytic activity of the nano silver modified electrode was compared with the silver electrode, and the catalytic activity of the modified electrode after repeated use was discussed. Simonet et al. electrodeposited silver nanoparticles on glassy carbon electrode, and explored a variety of organic halogenated compounds to study the universality of nano silver-modified electrodes in electrocatalytic reduction of organic halides.¹⁹On the other hand, numerous research efforts have been reported to control the morphology of metal nanoporous materials to obtain optimized activity in electrocatalysis. Mesoporous silver material has the advantages of large specific surface area, large pore volume, regular mesoporous structure, good chemical inertia, good ductility, good thermal stability and good conductivity, so it has been widely concerned. These properties are beneficial to heterogeneous catalytic reactions and other applications, such as adsorption/separation, fuel cells and biosensors.²⁰ However, mesoporous silver materials are mainly used to enhance the reproducibility and sensitivity of Raman scattering signals,²¹ and are rarely used in electrocarboxylation. How to improve the yield of electrocarboxylation by using mesoporous silver electrode and expand the application range of mesoporous silver materials is worthy of our efforts.In this study, we used hard template method to synthesize mesoporous silver for electrocatalytic carboxylation of halogenated compounds. Different mesoporous silver materials are obtained by adjusting the amount of silver nitrate solution.The experimental results show that mesoporous silver with different mesoporous pore sizes has different catalytic performance on the electrocatalytic carboxylation of halogenated compounds to acid under mild conditions.A series of mesoporous silver was synthesized by using hydrophobic mesoporous silica KIT-6 as template and silver nitrate as metal precursor (see the ESI^† for details),²² which are named as mesoAg-1, mesoAg-2, mesoAg-3, mesoAg-4 and mesoAg-5. The X-ray diffraction (XRD) patterns (Fig. 1) show that these five materials all have four characteristic peaks at 38.0°, 44.3°, 64.5° and 77.3° respectively, corresponding to the (111), (200), (220) and (311) face centered cubic crystal faces of the standard card PDF # 04-0783 of Ag, which indicates that these materials are metallic silver.Open in a separate windowFig. 1XRD patterns of (a) mesoAg-5, (b) mesoAg-4, (c) mesoAg-3, (d) mesoAg-2 and (e) mesoAg-1.Morphologies of mesoporous silver materials were characterized by scanning electron microscope (SEM) and transmission electron microscope (TEM). As shown in Fig. 2, mesoAg-3 material is composed of many nanoparticles with a diameter of 8 nm, which is close to the pore size of HP-KIT-6 template (Table S1 and Fig. S1^†). This indicates that the mesoporous structure of the template has been well duplicated. The morphologies of mesoporous silver prepared with the same quality template and different quality of silver nitrate solution are different (Fig. 2b and S2^†). The regular arrangement of mesoporous silver can be observed in the SEM images of mesoAg-3 and mesoAg-4. Moreover, the accumulation of silver in mesoAg-3 and mesoAg-4 is less than that of other three materials. In the SEM images of mesoAg-1, mesoAg-2 and mesoAg-5, not only the mesoporous structure of silver but also the accumulation of silver could be observed. It''s probably because in the process of preparing mesoporous silver, adding too much or too little silver nitrate solution will lead to incomplete replication of the mesoporous structure, resulting in larger particle size. If the mass of AgNO₃ solution is too much, it will lead to solution outside the template channel. Due to surface tension, part of the solution that should have been immersed in the channel will also be attracted to the outside of the channel. In addition, during the thermal decomposition process of preparing mesoporous silver, that is, the sample was heated to 573 K under nitrogen flow for 2 hours, the mesoporous structure of silver is only formed in the mesoporous of the template. However, the silver outside the template is easy to grow into large particles, resulting in the formation of massive silver.²² While the mass of AgNO₃ solution is too small, although the solution will exist in the channel, the channel is not completely saturated and the mesoporous structure is not completely replicated. These two conditions lead to the decrease of silver content in the mesoporous template, the formation of silver mesoporous structure is less, which may lead to the decrease of specific surface area and pore volume.Open in a separate windowFig. 2(a) TEM and (b) SEM images for mesoAg-3.N₂ adsorption desorption isotherms and corresponding BJH pore size distribution curves were measured for mesoporous silver materials (Fig. 3 and S3^†). As shown in Fig. 3, both mesoAg-3 and mesoAg-4 have obvious IV adsorption isotherms and H1 hysteresis loops in the specific pressure range of 0.45–0.75, which indicates that both samples have mesoscopic pore structure. H3 hysteresis loops appeared for mesoAg-1, mesoAg-2 and mesoAg-5, indicating that there are mutual accumulations of mesoporous silver in the materials, and the pore structure became irregular. It is consistent with SEM image (Fig. S2^†). Textural parameters of these mesoporous silver materials are summarized in Open in a separate windowFig. 3N₂ adsorption–desorption isotherms for the mesoporous silver materials.Structure parameters for mesoporous Ag

Access to 3,3-disubstituted oxindoles via microwave-assisted Cannizzaro and aldol reactions of formaldehyde with isatins and their imines

3,3-Disubstituted oxindoles are important structure motifs in natural products and pharmaceutical agents. Here we disclose a simple and direct access to this class of molecules by using readily available formaldehyde and isatins (and their imines) as the substrates. The reaction proceeds with the assistance of microwave heating in the presence of a mild base. Formaldehyde behaves as both a reductant (via a Cannizzaro process with isatin) and an electrophile.

The reaction proceeds with the assistance of microwave heating in a mild base. Formaldehyde behaves as both a reductant (via a Cannizzaro process with isatin) and an electrophile.

3,3-Disubstituted oxindoles are valuable structure motifs that have widely existed in biologically active natural products, alkaloids and pharmaceutical agents.^1,2 For example, TMC-95A and its analogues are isolated from Apoispora montagnei. They can be used as specific proteasome inhibitors.³ Paratunamide D from paratude or Cinnamodendron axillare (Canellaceae) has shown moderate cytotoxicity against human epidermoid carcinoma KB cells (IC₅₀ = 6 μg mL⁻¹).⁴ Convolutamydine A, which is isolated from the Floridian marine bryozoan Amathia convoluta, has exhibited significant antinociceptive effects.⁵ Maremycin B is another oxindole-containing natural product molecule that has been isolated from the Streptomyces species B 9173.⁶ The above natural products have shown proven biological activities such as antioxidant, antimicrobial or antitumor activities (Fig. 1a).⁷ Therefore, the synthesis of 3-hydroxyoxindole derivatives has long been interesting and attractive.⁸Open in a separate windowFig. 13-Hydroxyoxindole derivatives and their synthesis.3-Hydroxyoxindole derivatives are one class of the most basic functional molecules containing oxindole scaffolds. Traditionally, 3-hydroxyoxindoles are obtained through aldol reactions, Friedel–Crafts reactions, Morita–Baylis–Hillman reactions and Hosomi–Sakurai allylation reactions.⁹ In 2014, Hu and co-workers¹⁰ developed a rhodium(ii)-catalyzed three-component reaction for the synthesis of substituted 3-hydroxy(amino)-3-hydroxymethyloxindoles (Fig. 1b). Nobel metal catalysts and pre-functionalized diazo substrates are needed in this protocol.¹¹Herein, we describe a microwave assisted Cannizzaro/aldol reaction of paraformaldehyde and isatins (or its imine derivatives). Paraformaldehyde behaves as both a reductant¹² (via a Cannizzaro process with isatin) and an electrophile (Fig. 1c). Simple and inexpensive inorganic bases are applied as the only catalysts for this process, with the functionalized 3-hydroxymethyl-oxindole products afforded in good to excellent yields. N-Methyl isatin 1a and paraformaldehyde 2 were selected as the model substrates to evaluate the reaction condition for the synthesis of 3-hydroxy-3-hydroxymethyloxindole 3a ( EntryBaseSolventYield^b (%)1K₂CO₃EtOH (w/o MW)292—EtOHn.d.3K₂CO₃EtOH944Na₂CO₃EtOH465KOAcEtOH786 t-BuOKEtOH657DBUEtOH708Et₃NEtOH299K₂CO₃CH₃CN4710K₂CO₃Toluene5311K₂CO₃DMF49 12 ^c K ₂ CO ₃ EtOH 92 13^dK₂CO₃EtOH34Open in a separate window^aReaction condition: a mixture of 0.1 mmol of 1a, 1.5 mmol of 2, 20 mol% of base and 1.5 mL of solvent was irradiated in a microwave reactor at 120 °C for 15 min.^bYields are of isolated products based on 1a.^cPerformed at 100 °C.^dThe reaction mixture of 2 is 0.1 mmol in 100 °C microwave reactor. n.d. = no detected. DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene.Having established an optimal condition for the reaction, the scope of the isatin derivatives was examined ( Open in a separate window^aReaction condition: a mixture of 0.2 mmol of 1, 3.0 mmol of 2, 20 mol% of base and 1.5 mL of solvent was irradiated in a 100 °C microwave reactor with 15 min and yields are of isolated products based on 1.It is worth to note that the isatin-derived ketimine substrates 4 could also be used as suitable reactants for this microwave assisted Cannizzaro/aldol reaction process ( Open in a separate window^aReaction condition: a mixture of 0.2 mmol of 4, 3.0 mmol of 2, 20 mol% of base and 1.5 mL of solvent was irradiated in a 100 °C microwave reactor with 15 min and yields are of isolated products based on 4.A postulated reaction mechanism is depicted in Fig. 2. The paraformaldehyde can react with the hydroxyl group under basic condition to give the intermediate I, which can be further deprotonated to give the dianion intermediate II. A hydride shift between the intermediate II and isatin substrate 1 leads to the formation of the reduced oxindole intermediate III with the elimination of the formic acid as the byproduct. An aldol reaction between the intermediate III and the formaldehyde gives the desired product 3. To gain more insight into this mechanism, several control experiments were conducted. The 3-hydroxy-1-methylindolin-2-one instead of the isatin with K₂CO₃ as the catalyst gave desired product in 90% yield. Based on this control experiment, we proposed the mechanism is reasonable.Open in a separate windowFig. 2Postulated pathway.In summary, we have developed an efficient Cannizzaro/aldol reaction with the assistance of microwave irradiation. Paraformaldehyde and isatin derivatives are successfully used as the reaction substrates. Functionalized 3-hydroxymethyloxindole derivatives bearing various substituents and substitution patterns are afforded as the reaction products in good to excellent yields. Inexpensive and the readily available K₂CO₃ is applied as the only catalyst in this protocol. Further application of the 3-hydroxymethyloxindole derivatives obtained through this method in synthetic chemistry and investigations into novel microwave assisted transformation are currently in progress in our laboratory.     

DBU mediated one-pot synthesis of triazolo triazines via Dimroth type rearrangement

Herein we report an efficient one-pot synthesis of [1,2,4]triazolo[1,5 a][1,3,5]triazines from commercially available substituted aryl/heteroaryl aldehydes and substituted 2-hydrazinyl-1,3,5-triazines via N-bromosuccinimide (NBS) mediated oxidative C–N bond formation. Isomerisation of [1,2,4]triazolo[4,3-a][1,3,5]triazines to [1,2,4]triazolo[1,5-a][1,3,5]triazines is driven by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) affording both isomers with good to excellent yields (70–96%).

We demonstrate a simple yet efficient one-pot synthesis of two triazolotriazine isomers via DBU mediated Dimroth type rearrangement with excellent yields.

Purines are nitrogen-containing heterocycles and are structural motifs in the nucleobases adenine and guanine of DNA as well as RNA. Purine nucleotides (ATP, GTP, cAMP, cGMP, NAD, FAD) also act as co-factors, substrates, or mediators in the functioning of numerous proteins.¹ Therefore, bioisosteres of purines are widely explored and exploited by pharmaceutical chemists in developing new drug entities. Heterocycles containig the 1,3,5-triazine ring act as bioisosteres of purine, which exist as two isomers, namely [1,2,4]triazolo[4,3-a][1,3,5]triazine and [1,2,4]triazolo[1,5-a][1,3,5]triazine (Fig. 1), which have been extensively studied as adenosine receptor antagonists,^2,3 as well as for other pharmacological activities^1,4,5 (Fig. 2). Literature reports suggest that [1,2,4]triazolo[1,5-a][1,3,5]triazine has been exploited extensively in drug discovery as compared to its corresponding isomer. Further, from the literature it is evident that symmetrical disubstituted triazines,^6–9 especially morpholine^10–12 substituted, have displayed broad pharmacological activities.Open in a separate windowFig. 1Structure of isomers of triazolo–triazine.Open in a separate windowFig. 2Biologically active molecules of [1,2,4]triazolo[4,3-a][1,3,5]triazine (1) and [1,2,4]triazolo[1,5-a][1,3,5]triazine (2, 3, 4).Various synthetic methods have been reported for the C–N bond formation by employing different starting materials^13–15via oxidative cyclisation,¹⁶ high temperature condition^17–19 and/or metal-catalysed reactions.²⁰ However, the current reported protocols were environmentally unfriendly as they suffered from drawbacks such as, multistep, and tedious procedures, use of carcinogenic solvents, high-temperature, expensive and toxic metal-catalysts, and other hazardous reagents.Furthermore, there is very less reported research on these heterocycles, and that can be because of the unavailability of the efficient and cheaper methods. Thus, there is a need to develop new versatile synthetic method for the synthesis of disubstituted triazolotriazine heterocycles of pharmacological interest.In 1970, for the first time Kobe²¹et al. (scheme a) reported the synthesis of [1,2,4]triazolo[4,3-a][1,3,5]triazine utilizing lead tetraacetate in benzene under reflux conditions (Fig. 3). However, no further Isomerization was carried out and resulted low to moderate yield. Deshpande²²et al. reported (scheme b) the reaction of 2-hydrazinyl-1,3,5-triazine with various substituted benzoic acids. The product formed was treated with P₂O₅, refluxed in xylene for 10h to yield [1,2,4]triazolo[4,3-a][1,3,5]triazine. Further, Isomerization of the resulting product was carried out in 2% methanolic-NaOH solution resulting in poor yields. Recently, Stefano²³et al. (scheme c) reported, a multistep protocol by reacting the intermediate with bis(methyl-sulfanyl)methylenecyanamide at 180 °C under N₂ for 3h resulting in low yield due to the formation of several side products. In addition no isomerization studies were carried out, and only the [1,2,4]triazolo[1,5-a][1,3,5]triazine analogs were reported.Open in a separate windowFig. 3Different approaches for the synthesis of triazolo triazines.Herein, we report an economical one-pot synthesis of [1,2,4]triazolo[1,5-a][1,3,5]triazine analogs via Dimroth type rearrangement of [1,2,4]triazolo[4,3-a][1,3,5]triazine derivatives. This one pot novel methodology was carried out by reacting readily available, inexpensive starting materials such as substituted aryl/heteroaryl benzaldehydes and substituted 2-hydrazinyl-1,3,5-triazine in methanol (a mild solvent)²⁴ at room temperature giving excellent yields of the desired product. For cyclization reaction, an eco-friendly reagent NBS²⁵ was used and the resulting product was treated with DBU to yield its corresponding desired isomer. To the best of our knowledge this is the first report for the greener synthesis of symmetric disubstituted triazolotriazine heterocycles via Dimroth type rearrangement. We believe that this simple, yet novel methodology could be further exploited by the researchers in pharmaceutical industries and academics settings in drug discovery.Formation of the Schiff base was initiated reacting 4,4′-(6-hydrazinyl-1,3,5-triazine-2,4-diyl)dimorpholine 1a and unsubstituted benzaldehyde as shown in Entry no.SolventOxidantBaseBase equiv.Time (hour)Yield%1EtOHNBSDBU1.016682DCMNBSDBU1.01603DMFNBSDBU1.01604MeOHNBSDBU1.016725i-PrOHNBSDBU1.016Trace6H₂ONBSDBU1.01607MeOHNBS——1608MeOHNBS2%NaOH1.016Trace9MeOHNBSK₂CO₃1.016010MeOHNBSTEA1.016011MeOHNBSDABCO1.016012MeOHNBSDBU1.528513MeOHNBSDBU2.01.58014MeOHNCSDBU1.525615MeOHNISDBU1.526116MeOHIBDDBU1.526317MeOHKI/I₂DBU1.525318MeOH/H₂ONBSDBU1.5270Open in a separate window^aConditions: 1a (1 mmol), benzaldehyde (1 mmol), solvent, rt, 20 min, then oxidant (1 mmol), 5 min, rt, then DBU, stir at rt till completion of the reaction.Meanwhile, equivalents of DBU were adjusted (entry 12, 13) to attain the highest yield %. Reaction with 1.5 eq. showed drastic improvement in yields in 2 h whereas 2.0 eq. resulted in good yields with less reaction time. Considering the yield factor (entry 12), the oxidant optimization was achieved (entry 14–17). Using N-chlorosuccinimide (NCS) and N-iodosuccinimide (NIS) (entry 14, 15) offered 56% and 61% yield respectively. When the reaction was performed using phenyliodine(iii) diacetate (PIDA) and KI/I₂ (entry 16, 17) it provided 2a in 63% and 53% yields, respectively. Finally, methanol–water and ethanol–water systems in 3 : 1 were used, which gave approximately 70% yield, concluding that entry 12 gives the best result, demanding alcoholic solvents especially methanol as a key factor for Dimroth type rearrangement. Additionally, it was supported by the observation that reaction goes well in methanol, a little worse in ethanol (Fig. 4. The reaction involves a Schiff base formation (II) by 1a and benzaldehydes, the addition of NBS results in oxidative cyclization reaction to produce isomer 1. The addition of DBU in isomer-1 initiates a famous Dimroth type rearrangement, protonation of III results in ring-opening with the formation of unstable intermediate V. It undergoes tautomerism by 1,3 proton shift, bond rotation and proton abstraction by methoxide ion facilitating the intramolecular cyclization to afford the isomer 2. This reaction mechanism is supported by the formation of the Schiff base, isomer-1, and its conversion to isomer-2, which were easily monitored by TLC, isolated, and characterized (ESI^†). In addition to that, a single crystal of compound 2e was obtained, which further supports the Dimorth type of rearrangement (ESI^†).Open in a separate windowFig. 4Plausible mechanism of the reaction pathway.Having in hand the optimized conditions, the substrate scope was further explored by using different aldehydes (Fig. 5). The reaction was carried out using 1a with benzaldehydes having electron-donating groups (2a-f) followed by NBS and DBU additions. The reaction was allowed to stir at room temperature till reaction completion, as monitored by TLC, which would approximately take 2 h. The reaction could smoothly give final products in excellent reaction yields (79 to 96%). Electron withdrawing groups such as chlorobenzaldehydes (2g-i) despite the position of substitution gave excellent yields (93–95%). With the 4-bromo and different fluoro-benzaldehydes, the reaction resulted in 2j (89%) and 2k-m (84–90%) with very good yields. Also, reaction afforded 70% and 77% yields with heterocyclic aldehydes such as 3-pyridinecarboxyaldehyde (2n) and thiophene-2-carbaldehyde (2o), respectively.Open in a separate windowFig. 5Substrate scope for different aldehydes.The gram scale reaction was performed to further validate this synthetic procedure. The reaction was carried out using 1a (1 g) with benzaldehyde (0.38 g) and stirred for 30 min. The NBS (1.26 g, 1 eq.) was added slowly and stirred till new spot appeared on TLC followed by the slow addition of DBU (1.5 eq.) resulted in isomerisation to give 2a in good yields (1.1 g, 84%) (ESI^†).Encouraged from the potency of the reaction to generate in good to excellent yields [1,2,4]triazolo[1,5-a][1,3,5]triazine analogues, we shifted our investigation to isolate [1,2,4]triazolo[4,3-a][1,3,5]triazine derivatives (isomer-1) as described in Fig. 6. Different aldehydes were reacted with hydrazinyl-1,3,5-triazine analogs (1a, 3a, and 4a) and followed by the addition of NBS, stirred at room temperature till the completion of reaction as monitored by TLC. Compound 1a on reaction with 4-bromobenzaldehyde and NBS resulted in 1b with 90% yield. Similarly, 3a with 4-bromobenzaldehydes and thiophene-2-carbaldehyde afforded 3b and 3c with 84% and 83% yields, respectively. The same reaction was carried out with 4a and 4-bromobenzaldehyde bearing an electron-withdrawing group gave 3d with 87% yield. Further, 4a with aldehydes bearing electron-donating groups resulted 4c and 4d, with 88% and 84% yields, respectively (Fig. 7).Open in a separate windowFig. 6Substrate scope for [1,2,4]triazolo[4,3-a][1,3,5]triazine analogues.Open in a separate windowFig. 7Substrate scope for different disubstituted triazinyl-hydrazine and aldehydes.With these promising results, we explored the scope of aldehydes and 2-hydrazinyl-1,3,5-triazine analogs for the synthesis of [1,2,4]triazolo[1,5-a][1,3,5]triazine derivatives. Compound 3a, when reacted with different aldehydes and employing the optimized protocols gave 5a-e with excellent yields (86–92%) in 2–4 h. Similarly compounds 6a, 6b and 6c, synthesized from 4a also afforded excellent yields 88%, 86% and 90% respectively. Further, substituted cinnamaldehydes were also explored and reacted with 1a followed by the addition of NBS and DBU resulted in 7a and 7b in appreciable yields of 84% and 82%, respectively.Finally, we investigated both the isomers (3b and 5d) spectroscopically, to elucidate the change in proton chemical shifts during rearrangement. Interestingly, it was observed that the proton chemical shift for 5d at the 7th position (Fig. 6) was not affected. However, 5th position of 5d suffers a downfield shift due to change in its electronic environment as compared to its corresponding isomer 3b. In general, the proton chemical shifts for the substitution at 5th position and for the aromatic region was found to be more for isomer-2 as compared to isomer-1.     

Simple and efficient synthesis of bicyclic enol-carbamates: access to brabantamides and their analogues

A novel synthetic approach towards the formation of the unusual bicyclic enol-carbamates, as found in brabantamides A–C, is reported. The bicyclic oxazolidinone framework was obtained in very good yield and with high E/Z selectivity from a readily available β-ketoester under mild reaction conditions using Tf₂O and 2-chloropyridine tandem. The major E isomer was used in the synthesis of the brabantamide A analogue.

A simple and short synthesis of bicyclic enol-carbamates with high E/Z selectivity and the synthesis of brabantamide A analogue are presented.

Brabantamides A–C (1–3) (Fig. 1) were first isolated in 2000 from the culture extracts of Pseudomonas fluorescens.¹ They displayed nanomolar inhibitory activity towards lipoprotein-associated phospholipase A₂ (Lp-PLA₂) and therefore they could be used in the treatment of the inflammatory diseases such as atherosclerosis.^1–3 It was found that the sugar moiety is not necessary for the biological activity against Lp-PLA₂. In contrast, deglycosylated brabantamides A and C showed improved inhibitory activity compared to their natural counterparts.³ Moreover, simplified brabantamide analogues with amide functional group and long alkyl side chains showed even higher inhibitory effect.⁴ Brabantamides A–C also exhibit significant activity against Gram-positive bacteria, fungi, and oomycetes.^5,6 A recent study confirmed that the bicyclic scaffold and the long lipophilic side chain are essential for the antibacterial activity.⁷Open in a separate windowFig. 1Structures of brabantamides A–C (1–3). Rha = rhamnose.Surprisingly, only five reports concerning the synthesis of the bicyclic oxazolidinone with an exocyclic double bond have been reported to date.In 2000, Pinto et al. prepared a series of analogues of brabantamide A where the enol-carbamate 5 was first obtained by direct iodocyclization from acetylene derivative 4 and then converted into key ester 6 by carbonylation of the corresponding vinyl iodide in the presence of 2-(trimethylsilyl)ethanol and PdCl₂ (Scheme 1a).⁴ Another synthesis of the related esters 9 has been reported by Snider et al. in 2006, employing Wittig reaction between stabilized ylides and bicyclic oxazolidindione 8 synthesized from l-proline 7 (Scheme 1b).⁸ Shortly after, bicyclic enol-carbamate 10 with an exocyclic methylene group was synthesized in one step from acetylene derivative 4 using gold(i) catalysts (Scheme 1c).⁹ Very recently, Witte et al. reported the synthesis of series of Z-analogues of brabantamides 12 by cyclization of β-ketoamides 11 using CDI (Scheme 1d).⁷ As a part of our ongoing research program aimed at the utilization of trifluoromethanesulfonic anhydride (Tf₂O)/2-halopyridine (2-XPy) tandem in the synthesis of bioactive natural products and their analogues, we envisioned that similar reaction conditions could be effectively used to form the bicyclic oxazolidinone framework as found in brabantamides.Open in a separate windowScheme 1Literature syntheses of bicyclic enol-carbamates and method proposed herein.The combination of Tf₂O/2-XPy was extensively and successfully used in the amide activation^10,11 as well as in generating isocyanate species from N-Boc and N-Cbz protected amines.¹² We anticipated that the N-Boc-protected β-ketoester 13 could react in its enolate form with in situ generated isocyanate ion by intramolecular 5-endo-dig cyclization to give bicyclic enol-cyclocarbamate 14 (Scheme 1e).At the start of our investigation, model β-ketoester 15, prepared from N-Boc-l-proline,⁷ was chosen as the model substrate to identify optimal reaction conditions (12c the initial using of 1.5 equivalents of Tf₂O and 3 equivalents of 2-ClPy led to a full conversion of the substrate 15 in 15 minutes (monitored by TLC) (13 Any variation of the amount of 2-ClPy did not have any positive impact on the reaction ( EntryTf₂OBaseTime (min)16a : 16b^aYield^b (%)11.5—60—–^c21.5Et₃N60—–^c31.5DMAP60—–^c41.5Pyridine60—–^c51.5^d2,6-Lutidine60—–^c61.5^dDBU6090 : 1041^e,f71.52-ClPy1593 : 753^e 8 1.1 2-ClPy 15 85 : 15 80 ^e 91.12-ClPy (1.5 equiv.)4085 : 1575^e101.12-ClPy (5 equiv.)1587 : 1364^e111.12-FPy1589 : 1171^e121.12-BrPy7086 : 1473^e131.12-IPy9086 : 1468^e14Witte''s protocol^gOvernight50 : 5036^eOpen in a separate window^aRatio determined by ¹H NMR of the crude reaction mixture.^bIsolated combined yield.^cTraces of products.^dReactions performed with 1.1 equiv. of Tf₂O did not lead to full conversion of ester 15.^eReactions were performed on 1 mmol of ester 15.^fReaction mixture contained a large amount of unidentified by-products.^gReaction conditions: (1) TMSOTf (2 equiv.), CH₂Cl₂, 0 °C, 1 h. (2) CDI (1.5 equiv.), CH₂Cl₂, 0 °C – rt, overnight.⁷It is noteworthy that the reaction can be performed on a gram scale without affecting the yield and both isomers are easily separable by FCC (see the ESI^†).The ¹H and ¹³C NMR data of the major E isomer 16a were consistent with those published previously.⁸ Possible racemization in the course of the reaction was dismissed based on the comparing specific optical rotation with the published data for 16a ([α]²²_D = −261.1 (c 1.01, MeOH); ref. 8: [α]²²_D = −207 (c 1.0, MeOH)). Most importantly, X-ray crystallographic analysis of 16a (Fig. 2; see the ESI^† for further details)¹⁴ confirmed its absolute configuration on the C-7a carbon atom.Open in a separate windowFig. 2Molecular structure of the enol-carbamate E-16a confirmed by X-ray crystallographic analysis.The minor Z isomer 16b was isolated for the first time as the pure compound and was fully characterized. Its structure was assigned on the basis of its ¹H, ¹³C, COSY, HSQC, and HMBC NMR spectra.A plausible mechanism of the cyclization of β-ketoester 15 was based upon previous works^12a–c and it is depicted in Scheme 2. Isocyanate cation II, as a key intermediate, can be formed directly from iminium triflate I (path A) or through the formation of carbamoyl triflate III with subsequent elimination of triflate ion spontaneously (path B). Ester enolate moiety IV then reacts as O-nucleophile via 5-endo-dig cyclization and leads predominantly to the formation of the enol-carbamate 16a.Open in a separate windowScheme 2Plausible mechanism of the cyclization β-ketoester 15.Next, the optimized conditions were briefly applied in the synthesis of the brabantamide A analogue 21 (Scheme 3). Starting β-ketoester 18 was synthetized in two steps in a 70% yield using both commercially available N-Boc-d-proline 17 and 2-(trimethylsilyl)ethanol. It ought to be mentioned that previously examined hydrolysis of the corresponding methyl ester 16a under acidic as well as basic conditions failed due to the instability of the bicyclic enol-carbamate.^3,8Open in a separate windowScheme 3Synthesis of the brabantamide A analogue 21.Subsequent cyclization of ester 18 using optimized reaction conditions afforded enol-carbamate 19 in 76% yield as a mixture of E and Z isomers in a ratio of 89 : 11. After isolation of the major isomer E-19a, it was treated with TBAF, providing free acid 20 in 89% yield. Finally, an amidation of 20 with tetradecylamine in the presence of EDCI gave amide 21 in moderate 40% yield. Both free acid 20 and amide 21 were fully characterized for the first time and their structures were assigned on the basis of its ¹H, ¹³C, COSY, HSQC, and HMBC NMR spectra. Moreover, their structures were unambiguously confirmed by X-ray crystallographic analysis (Fig. 3; see ESI^† for further details).¹⁴Open in a separate windowFig. 3Molecular structures of acid 20 (top) and amide 21 (bottom) confirmed by X-ray crystallographic analysis.     

Flexible cupric oxide photocathode with enhanced stability for renewable hydrogen energy production from solar water splitting

CuO is a promising but unstable photocathode in solar water splitting. Herein, a flexible CuO photocathode is prepared and its degradation mechanisms and stabilization strategies have been discussed. Briefly, we find alkali environment and low light intensity are the critical factors in the stabilization of the CuO photocathode. For practical usage, a composite semiconductor layer, composed of TiO₂, La₂O₃ and NiO, is deposited on the CuO photocathode, which is proved to be effective for enhancing the stabilization of the CuO photocathode. 100% of the photocurrent density has been retained after 20 minutes of continuous illumination. The optimized stable photocurrent density is measured as 0.3 mA cm⁻² at 0.5 V_RHE.

A composite semiconductor layer, composed of TiO₂, La₂O₃ and NiO, is deposited on a CuO photocathode, and shown to be effective for enhancing the stabilization of the CuO photocathode. 100% of the photocurrent density is retained after 20 min of continuous illumination.

The lack of suitable photocathode materials for water reduction seriously limits the development of solar water splitting.^1,2 Cupric oxide (CuO) is an attractive cathode candidate for photoelectrochemical (PEC) water splitting due to its narrow band gap (1.44–1.68 eV), low cost, and nontoxicity.³ Nonetheless, the enormous potential of the CuO photocathode has not received enough attention probably because the conduction band was considered to be more positive than the potential of the water reduction reaction (0 V versus NHE, Normal Hydrogen Electrode) from the theoretical calculation, and unfavorable for hydrogen production.⁴ More seriously, copper-based oxides, including CuO and Cu₂O, suffer from fast photo-induced corrosion, whose stabilities are far from those of the typical photoanodes, such as WO₃ and α-Fe₂O₃.^5,6 For decades, scientists dreamt of stabilizing the CuO photocathode in aqueous electrolytes at comparatively low potentials, especially at 0 V_RHE (RHE = Reversible Hydrogen Electrode), and there are few successful cases.¹ The direct reason is probably the unsolved degradation mechanism and the complex side effects of CuO photocathode in the water splitting reaction. Herein, we report a facile and highly effective low-cost strategy based on synthesizing flexible CuO photocathode, followed with the analyses of the influence of electrolyte environment, bias potential and light intensity on CuO photocathode stability, at last we designed a multiple overlayer, which takes into consideration of advantages of each individual layer. The optimized CuO shows remarkably enhanced photo-stability with 100% retention of the photocurrent density after 20 min.From the SEM images in Fig. 1a, we can see the pre-clean Cu foil exposed a comparatively smooth morphology. After a fast fire treatment, a dense and brunette oxide layer grew on the metal surface. The oxide layer thickness increases as the fire treatment period extends. The average film thickness is 150 nm after 10 s of the fire treatment confirmed by the cross section SEM images, which is much thinner in comparison with the traditional calcination in a muffle furnace.⁷ The moderate thickness is convenient for the separation of charge carriers, preventing fast recombination.⁸ The metal interlayer serves to transfer electrons, while the oxide layer is responsible for absorbing photons and generating free electrons. Fig. 1b implies the fast fire treatment caused thermal expansion and contraction, produced a rough and wrinkled oxide layer.Open in a separate windowFig. 1SEM images of (a) the Cu foil and (b) the CuO photocathode, respectively; (c) cyclic voltammetry of the CuO photocathode in 1 M NaSO₄ electrolyte (pH 7); (d) dark current density of the CuO photocathode at 0 V_RHE in pH 7 without any photoresponse.It is a common that acidic electrolytes benefit hydrogen evolution reaction, because of high concentrations of protons.⁹ In previous studies, most of the colleagues try their best to improve the performance of CuO photocathode in Na₂SO₄ electrolyte.^10,11 However, the cyclic voltammetry in Fig. 1c demonstrates that Cu⁽²⁺⁾O spontaneously corrupts to Cu⁽⁰⁾ below 0.3 V_RHE (eqn (1)), which is buttressed by our photoelectrochemical test in Fig. 1d, predictably, the CuO photocathode deactivated abruptly in dark (the dark current density reached 93 mA cm⁻² at 0 V_RHE), and totally no photocurrent can be observed under illumination (the dark current density decayed to a stable value of 0.5 mA cm⁻²). After the reaction, the brunette absorbing layer disappeared, recovered a shiny metallic luster.CuO + 2e⁻ + 2H⁺ → Cu + H₂O, E^θ = +0.3 V_RHE1To avoid the fast self-corrosion of the CuO photocathode below 0.3 V_RHE, at the same time for the further combination with the photoanodes, we increased the voltage applied to CuO photocathode to 0.5 V_RHE, and at this time we found a photocurrent spike of 0.8 mA cm⁻² appeared, followed by a continuous decrease to 0.1 mA cm⁻² after 1000 s irradiation in Fig. 2a. The result implies that a slow deactivation process still exists, similar to the phenomenon in Jang''s work.³ In the retardatory deactivation process, the surface Cu⁽²⁺⁾O is reduced to Cu⁽⁰⁾, eqn (1), by the energetic photo-induced electrons. The accumulated Cu layer isolates the inner CuO from the electrolyte, which slows down the current decay. The extreme instability of CuO photocathode forced us to find a new path of using it.Open in a separate windowFig. 2(a) The photoelectrochemical stabilities of the CuO photocathodes in 1 M Na₂SO₄ (pH 7) and 1 M NaOH (pH 13) electrolytes at 0.5 V_RHE, respectively; (b) schematic plot of the band structure and photodeactivation mechanism of the CuO photocathode.After realizing that CuO is extremely sensitive to protons, which causes fast photo-induced inactivation, we tried to raise the pH value and reduce the proton concentration. Adjusting pH value is often an effective means for changing the course of a chemical reaction.^12,13 After substituting NaOH for Na₂SO₄ in the electrolyte, we discovered that the CuO photocathode produced a photocurrent density of 1.2 mA cm⁻² at 0.5 V_RHE in pH 13 without any decay during 1000 s. It is meaningful to find adjusting pH value has an ability to alter the selectivity of the CuO photocathode, which seems the easiest way to stabilize the CuO photocathode. As shown in Fig. 2b, according to the previous studies, the Fermi level of CuO is near to 0.8 V_RHE, while the calculated band gap is 1.6 eV.^3,14 As CuO is a p-type semiconductor, assuming that the energy gap between Fermi level and valence band is 0.3 eV,^15,16 the conduction band and valence band are −0.5 V_RHE and 1.1 V_RHE, respectively. Consequently, in the neutral condition, photo-excited electrons in the conduction band move downward and reduce surface CuO to Cu. As a result, we observed a fast descent of the photocurrent density. As mentioned above, the accumulated Cu layer isolates the inner CuO from the electrolyte, which slows down the current decay. Comparatively, photo-induced electrons selectively reduce water into hydrogen in the basic environment, while the deactivation reaction is somewhat neglected. The least of perfection, in the basic solution the good stability was accompanied by a slow recovery of the dark current.⁴CuO + H₂O + 2e⁻ → Cu + 2OH⁻, E^θ = +0.3 V_RHE2After tuning the light intensity from 100 mW cm⁻² to 20 mW cm⁻², it is really interesting to find the relaxation of dark current disappeared, although the photocurrent density decreased to 0.3 mA cm⁻². It is not difficult to associate this relationship with the shift of Fermi level. We interpret the mechanism in Fig. 3, under the powerful beam, the Fermi level transfers to the potential that is higher than the E^θ(Cu/CuO), in this case, the photo-excited electrons partially reduce surface CuO to Cu (eqn (2)), followed by generating Cu(OH)₂ spontaneously (eqn (3)). Cu(OH)₂ is a weak p-type semiconductor, leading to the relaxation phenomenon. Oppositely, the Fermi level stays below the E^θ(Cu/CuO) under low light intensity, which inspires the photo-electrons to fulfill the water reduction. Consequently, CuO photocathode shows a satisfactory photo-stability at 0.5 V_RHE with 100% retention of the photocurrent density after 20 min.Cu + 2OH⁻ + 2h⁺ → Cu(OH)₂, E^θ = −0.2 V_RHE3Open in a separate windowFig. 3The comparison of the mechanism at pH 13 under high light intensity (100 mW cm⁻²) and low light intensity (20 mW cm⁻²).As known to all, the power of sunlight varies with time in real life, it is really difficult to limit the maximum value from 100 mW cm⁻² to 20 mW cm⁻². Afterwards, we designed a triple-component protective layer of TiO₂/La₂O₃/NiO to neutralize the disadvantage, the thicknesses of TiO₂, La₂O₃ and NiO were 50 nm, 100 nm and 18 nm, respectively. The different film thicknesses were obtained by controlling the dip-coating processes (ESI^†). The multilayer structure not only controls the light intensity within an appropriate range but also has a catalytic influence. The TiO₂ wrapped the CuO surface and reduced the surface roughness in Fig. 4a, while the subsequent La₂O₃/NiO totally covered the substrate, making the surface smooth under the electron microscope (Fig. 4b). The optimized CuO photocathode (Fig. 4c) produced a thoroughly stable photocurrent density of 0.3 mA cm⁻² at 0.5 V_RHE under AM 1.5 G condition for 20 min, meanwhile, the dark current density recovers quickly and keeps steady, shown in Fig. 5a.Open in a separate windowFig. 4The surface SEM images of (a) the CuO/TiO₂ and (b) the CuO/TiO₂/La₂O₃/NiO; (c) schematic plot of the preparation of the CuO/TiO₂/La₂O₃/NiO photocathode.Open in a separate windowFig. 5(a) Photoelectrochemical response and stability of the TiO₂/La₂O₃/NiO coated CuO photocathode; (b) Cu LMM, Ti 2p, La 3d and Ni 2p X-ray photoelectron spectra (XPS) of the TiO₂/La₂O₃/NiO coated CuO photocathode; (c) schematic plot of the band structure and water reduction mechanism of the TiO₂/La₂O₃/NiO coated CuO photocathode; (d) gas evolution from the CuO/TiO₂/La₂O₃/NiO photocathode and the Pt counter electrode, which is compared with the evolution of H₂ (e⁻/2) and O₂ (e⁻/4) expected from the photocurrent. The measurement was performed at constant potential 0.5 V vs. RHE.The high stability of around 100% is found to be the highest reported value in terms of a plain CuO photocathode (Fig. 5b. X-ray induced Auger electron spectroscopy (XAES) was employed in the Cu LMM region to get information of the oxidation state of Cu (Fig. 5b), as the Cu 2p binding energies are almost indistinguishable. The Cu LMM peak at 917.7 eV was assigned to Cu²⁺. The binding energies of Ti 2p_3/2, La 3d_5/2 and Ni 2p_3/2 were 458.7, 834.5 and 835.7 eV, respectively, corresponding to Ti⁽⁴⁺⁾, La⁽³⁺⁾ and Ni⁽²⁺⁾. Furthermore, the XPS spectra before and after reactions in Fig. S1^† indicate the metal oxidation states in Cu⁽²⁺⁾O, Ti⁽⁴⁺⁾O₂, La⁽³⁺⁾₂O₃ and Ni⁽²⁺⁾O did not change after 30 min reaction, which met our expectations. Moreover, the construction of this multi-layer photocathode is depicted in Fig. 5c. Many researchers predicted that the conduction band position of CuO is not negative enough to drive the hydrogen evolution reaction. In fact, we found CuO possesses a conduction band edge near to −0.5 V_RHE, which means the photoelectrocatalytic hydrogen evolution from water by CuO should be thermodynamically favorable. In the present work, the photo-induced electrons in p-CuO were driven by the depletion layer (p-CuO/n-TiO₂ p–n junction) to n-TiO₂, then penetrated the La₂O₃ layer. Herein, La₂O₃ can be considered as a proton insulating layer.¹⁷ After hundreds of attempts, we found that La₂O₃ is one of the materials that effective for the stabilization of copper oxide, and the stability enhanced with the increasing thickness, until a thickness of 100 nm can balance the stability and the activity. Although La₂O₃ has a large theoretical band gap (3.8–5.8 eV), it contains deep levels and trap-states, which reduce the band gap (2.9 eV, fluorescence emission at 416 nm) and the resistivity (∼10 kΩ cm).^18–20 The deep levels and trap-states form intermediate levels in the large band gap, facilitating the charge transportation. Thus, La₂O₃ accepts the photo-induced electrons from TiO₂ and allow them to pass through. Finally, the electrons enter a second depletion layer, as p-NiO equilibrates with the electrolyte, and complete the water reduction. By the way, we have to mention that TiO₂, La₂O₃ and NiO perform their respective duties and are indispensable. The amounts of H₂ and O₂ that evolved were determined by gas chromatography. In Fig. 5d, the theoretical amounts of gases expected from photocurrent generations are compared with the actual generation of the gases. The difference between these two values is represented by the faradaic efficiency. The faradaic efficiency of the hydrogen evolution was determined to be 94% when the system was stabilized and showed a steady state. The rest 6% could be accounted for the inefficient gas collection (gas dissolution and strong adsorption on the electrode surface) and some parasitic electrochemical processes.The stabilities of the CuO photocathodes for PEC water splitting in the literature