Asymmetric synthesis of polysubstituted chiral chromans via an organocatalytic oxa-Michael-nitro-Michael domino reaction

A catalytic asymmetric method for the synthesis of polysubstituted chromans via an oxa-Michael-nitro-Michael reaction has been developed. The squaramide-catalyzed domino reaction of 2-hydroxynitrostyrenes with trans-β-nitroolefins produced chiral chromans with excellent enantioselectivities (up to 99% ee), diastereoselectivities (up to >20 : 1 dr), and moderate to good yields (up to 82%).

A catalytic asymmetric method for the synthesis of polysubstituted chromans via an oxa-Michael-nitro-Michael domino reaction of 2-hydroxynitrostyrenes with trans-β-nitroolefins has been accomplished.

Chromans play an essential role in natural products and pharmaceutical molecules (Fig. 1).¹ Given the biological relevance and diverse applications of this indispensable structural motif, numerous valuable methods for building chiral chromans have been developed.² Rapid, direct, and highly atom-economical asymmetric strategies to construct optically active chromans are the first choice.Open in a separate windowFig. 1Selected biologically active compounds.In the past several years, considerable effort has been made to build chiral chroman derivatives with multichiral centers via asymmetric domino reactions³ catalyzed by aminocatalysts,⁴ thiourea organocatalysts⁵ squaramide organocatalysts,⁶ and other organocatalysts.⁷ Among these approaches, the addition to nitroolefins is a simple but highly efficient route to obtain chiral chromans containing nitro-group, and the nitro group can often lead to changes in chemical and physical properties.^{4d–h,4j,5b–d} In 2013, Zhu et al. reported the organocatalytic oxa-Michael-Michael cascade strategy for the construction of spiro [chroman/tetrahydroquinoline-3,3′-oxindole] scaffolds from 2-hydroxynitrostyrenes and N-Boc-protected methyleneindolinones using a squaramide-cinchona bifunctional catalyst.^6a Peng et al. disclosed the highly efficient synthesis of polysubstituted 4-amino-3-nitrobenzopyrans from 2-hydroxyaryl-substituted α-amido sulfones and nitroolefins mediated by chiral squaramides.^6b Furthermore, Yan and Wang''s group developed the squaramide-catalyzed cascade reaction of 2-hydroxychalcones with β-CF₃-nitroolefins to yield CF₃-containing heterocyclic compounds with a quaternary stereocenter.^6c Notably, a general strategy for the synthesis of chiral chromans bearing two nitro moieties was never reported, especially for 2-alkyl-substituted chromans. In 2003, an easy and efficient method for the synthesis of 3-nitrochromans via the reaction of 2-hydroxynitrostyrenes and trans-β-nitroolefins in the presence of DABCO was reported.⁸ Motivated by our previous work concerning the asymmetric synthesis of chromans,^4i,9 this paper presents a highly efficient asymmetric method for the synthesis of polysubstituted chiral chroman derivatives, especially 2-alkyl-substituted chiral types, from 2-hydroxynitrostyrenes and trans-β-nitroolefins using a chiral bifunctional squaramide organocatalyst.^10,11Given these considerations and previous work, the organocatalytic oxa-Michael-nitro-Michael reaction was performed with 2-hydroxynitrostyrene 1a and aliphatic trans-β-nitroolefin 2a as model substrates to examine the feasibility of our approach. Different parameters (5c,d An appropriate basic/nucleophilic moiety is critical to this kind of reaction. Under this consideration, chiral 1,2-diphenylethylenediamine, cyclohexanediamine, and quinine were selected as scaffolds. After a preliminary study, the quinine scaffold revealed excellent stereoinduction for the asymmetric synthesis of the chiral chroman 4a when paired with the squaramide unit (

Synthesis of benzoxazoles via an iron-catalyzed domino C–N/C–O cross-coupling reaction

An eco-friendly and efficient method has been developed for the synthesis of 2-arylbenzoxazoles via a domino iron-catalyzed C–N/C–O cross-coupling reaction. Some of the issues typically encountered during the synthesis of 2-arylbenzoxazoles in the presence of palladium and copper catalysts, including poor substrate scope and long reaction times have been addressed using this newly developed iron-catalyzed method.

The synthesis of benzoxazoles via an iron-catalyzed cascade C–N and C–O coupling is described.

2-Arylbenzoxazoles are an important class of structures in natural products, and pharmaceuticals and has shown a wide range of biological activities, such as antitumor, antiviral, and antimicrobial activities.¹ In particular, they show a marvellous efficacy in the treatment of duchenne muscular dystrophy (DMD) which is one of the most common of the muscular dystrophies that is caused by a mutation in the gene DMD, located in humans on the X chromosome (Xp21).² So the synthesis of 2-arylbenzoxazoles has been intensively studied for use in organic and medicinal chemistry over the past few years.Numerous methods have been reported to synthesise this motif, one of the common methods is transition-metal-catalyzed (like Pd,³ Ni,⁴ Cu,⁵ Mn⁶etc.) cross-coupling from pre-existing benzoxazoles with aryl halide or arylboronic acid. And another method is the classic one employing a cyclocondensation approach between an aminophenol and either a carboxylic acid⁷ or benzaldehyde⁸ (Scheme 1, path a). In 2004, Frank Glorius'' group reported a domino copper-catalyzed C–N and C–O cross-coupling for the conversion of primary amides into benzoxazoles⁹ (Scheme 1, path b) which is a new reaction type for the synthesis of benzoxazoles. Bunch et al. apply this domino reaction in the synthesis of planar heterocycles in 2014.¹⁰ In addition the cyclization of o-halobenzenamides to benzoxazoles has been reported several times.^11,12 Nevertheless, some limitations in the reported methods need to be overcome, such as the use of palladium complexes and narrow substrate range.Open in a separate windowScheme 1Classic method of benzoxazole formation.In the last few years, there has been a significant increase in the number of reports pertaining to the development of iron-catalyzed reactions in organic synthesis, where iron has shown several significant advantages over other metals, such as being more abundant, commercially inexpensive, environmentally friendly and drug safety.¹³ Compared with palladium and copper, the use of iron is particularly suitable for reactions involving the preparation of therapeutic agents for human consumption. With this in mind, it was envisaged that an new method should be developed for the synthesis of benzoxazoles via an iron-catalyzed domino C–N/C–O cross-coupling reaction.The reaction of benzamide (1a) with 1-bromo-2-iodobenzene was used as model transformation to identify the optimum reaction conditions by screening a variety of different iron salts, bases, ligands and solvents (l-proline provided no product (14 high-purity Fe₂O₃ (99.999%) and K₂CO₃ (99.999%) were applied in the reaction ( EntryIron saltLigandBaseSolvent Y ^b (%)1FeCl₃DMEDAKO^tBuPhMeTrace2FeCl₂·4H₂ODMEDAKO^tBuPhMeTrace3FeSO₄·7H₂ODMEDAKO^tBuPhMe04Fe(acac)₃DMEDAKO^tBuPhMe05Fe₂O₃DMEDAKO^tBuPhMe156Fe₃O₄DMEDAKO^tBuPhMe07Fe₃O₄(nano)DMEDAKO^tBuPhMe108Fe₂O₃(nano)DMEDAKO^tBuPhMe09Fe₂(SO₄)₃DMEDAKO^tBuPhMe010Fe(NO₃)₃·9H₂ODMEDAKO^tBuPhMe011Fe₂O₃DMEDALiO^tBuPhMe012Fe₂O₃DMEDANa₂CO₃PhMe013Fe₂O₃DMEDANaOAcPhMe014Fe₂O₃DMEDAKOHPhMe015Fe₂O₃DMEDAK₂CO₃ (24 h)PhMe3716Fe₂O₃DMEDAK₂CO₃ (48 h)PhMe8717Fe₂O₃PhenK₂CO₃PhMeTrace18Fe₂O₃ l-ProlineK₂CO₃PhMe019Fe₂O₃DpyK₂CO₃PhMe020Fe₂O₃DMEDAK₂CO₃DMSO021Fe₂O₃DMEDAK₂CO₃DMF022Fe₂O₃DMEDAK₂CO₃PhMe₂023—DMEDAK₂CO₃PhMe024Fe₂O₃DMEDAK₂CO₃PhMe86^c25Fe₂O₃DMEDAK₂CO₃PhMe58^dOpen in a separate window^aReaction conditions: benzamides (0.5 mmol), 1-bromo-2-iodobenzene (1.5 eq.), iron salt (20% mol), base (1 eq.), ligand (20%) were added to a solvent (2 mL) and react at 110 °C for 48 h under N₂.^bIsolated yield based on 1a after silica gel chromatography.^cFe₂O₃ and K₂CO₃ were applied in purity of 99.999% from alfa.^dwith Fe₂O₃ in a dosage of 10 mmol%.At last, the dosage of Fe₂O₃ was reduce to 10 mmol%, but only 58% yield was obtained (Scheme 2.Open in a separate windowScheme 2The pathway of the reaction.With the optimized reaction conditions in hand, we proceeded to investigate the substrate scope of the reaction using a variety of different 1,2-dihalobenzene substrates and aryl formamide ( Open in a separate window^aReaction conditions: 1a (0.5 mmol), o-dihalo substrate (1.5 eq.), Fe₂O₃ (20% mol), K₂CO₃ (1 eq.), DMEDA (20%) were added to PhMe (2 mL) and react at 110 °C for 48 h under N₂.Based on the results observed in the current study and Goldberg reaction,¹⁵ we have proposed a reaction mechanism for this transformation, which is shown in Scheme 3. The initial transmetalation of benzamide with Fe₂O₃L_n in the presence of K₂CO₃ would give rise to the iron(iii) species A. Complex A would then undergo an oxidative addition reaction with 1-bromo-2-iodobenzene to give the iron(v) species B, which would undergo a reductive elimination reaction to give iron(iii) species C with the concomitant formation of a C–N bond. Followed the tautomerism of intermediate C to D, the intermediate iron(iii) species E was formed in the presence of K₂CO₃, which would undergo another oxidative addition reaction to afford iron(v) species F. Compound 3a would then be obtained via a reductive elimination reaction from iron(v) species F.Open in a separate windowScheme 3Possible catalytic cycle.In summary, we have demonstrated that the cheap and environmental friendly catalyst system composed of Fe₂O₃ and ligand DMEDA is highly effective for the synthesis of 2-arylbenzoxazoles. The new catalyzed system can be effective for both C–N coupling and C–O coupling.     

An efficient and green synthesis of ferrocenyl-quinoline conjugates via a TsOH-catalyzed three-component reaction in water

An efficient and green synthesis of 4-ferrocenylquinoline derivatives through a TsOH-catalyzed three-component reaction of aromatic aldehydes, amines and ferrocenylacetylene in water has been successfully developed. This strategy is a powerful method for the construction of diverse ferrocenyl-quinoline conjugates from simple available starting materials as it minimized the use of metal catalyst and organic solvent in the reaction process. The conjugates feature unique structures and excellent electronic properties. Moreover, a plausible mechanism for this TsOH-catalyzed three-component reaction was proposed and assessed.

We have successfully developed a green method for facile and efficient synthesis of ferrocenyl-quinoline conjugates from available starting materials via a TsOH-mediated three-component reaction in water.     

An efficient and ecofriendly synthesis of highly functionalized pyridones via a one-pot three-component reaction

A simple and convenient protocol has been developed for the synthesis of N-amino-3-cyano-2-pyridone derivatives by a one-pot reaction of cyanoacetohydrazide, activated nitrile substrates (malononitrile, ethyl cyanoacetate, cyanoacetamide) and aromatic aldehydes in the presence of piperidine in water or a mixture of water and ethanol. The sequence of cascade reactions includes Knoevenagel condensation, Michael addition, intramolecular cyclization, imine-enamine tautomerization and oxidative aromatization. The main advantages of this procedure are availability of starting compounds, simple procedure, mild conditions, easy purification of products and the use of water or water/ethanol as green solvents.

Synthesis of N-amino-3-cyano-2-pyridone derivatives in green solvent with simple procedure and high purity via a one-pot operation.     

Copper-catalyzed synthesis of 2-aminopyridylbenzoxazoles via domino reactions of intermolecular N-arylation and intramolecular O-arylation

A simple and general approach to nitrogen-containing heterocycles via copper-catalyzed domino reaction has been developed, and the corresponding 2-aminopyridylbenzoxazole derivatives were obtained in good to excellent yields using the readily available starting materials. This method possesses unique step economy features, and is of high tolerance towards various functional groups in the substrates.

A simple and general approach to nitrogen-containing heterocycles via copper-catalyzed domino reaction has been developed, the corresponding 2-aminopyridylbenzoxazole derivatives were obtained in good to excellent yields using the readily available starting materials.     

ZnCl2-promoted domino reaction of 2-hydroxybenzonitriles with ketones for synthesis of 1,3-benzoxazin-4-ones

A ZnCl₂-promoted synthesis of 1,3-benzoxazin-4-one from 2-hydroxybenzonitriles and ketones was developed. This method displays facile access to a diverse range of substituted 1,3-benzoxazin-4-ones in good yields. This synthetic protocol has advantages: (i) easy availability of starting material; (ii) strong corrosive acid-free condition; (iii) high yield.

A method for the synthesis of 1,3-benzoxazine-4-ketone was developed using 2-hydroxybenzonitriles and ketones as raw materials with the promotion of ZnCl₂.     

Palladium mediated domino reaction: synthesis of isochromenes under aqueous medium

Isochromenes have been synthesized using palladium-catalyzed C–C and C–O bond forming reactions starting from ortho-bromo tertiary benzylic alcohols and internal acetylenes. Notably, this domino process is feasible by using the green solvent, water. The protocol exhibited a broad substrate scope and afforded various isochromenes.

Isochromenes have been synthesized using palladium-catalyzed C–C and C–O bond forming reactions starting from ortho-bromo tertiary benzylic alcohols and internal acetylenes.     

A multi pathway coupled domino strategy: I2/TBHP-promoted synthesis of imidazopyridines and thiazoles via sp3, sp2 and sp C–H functionalization

I₂/TBHP-promoted, one-pot, multi pathway synthesis of imidazopyridines and thiazoles has been achieved through readily available ethylarenes, ethylenearenes and ethynearenes. I₂/TBHP as an initiator and oxidant is used to realize the C–H functionalization of this domino reaction. Simple and available starting materials, wide range of functional group tolerance, high potential for drug activity of the products and application in production are the advantageous features of this method.

One-pot, multi-pathway, and atom economic synthesis of imidazoles and thiazoles has been achieved. In the catalytic system, I₂/TBHP as an initiator and oxidant is used to realize sp³, sp² and sp C–H functionalization.     

Efficient synthesis of 1-iodoalkynes via Al2O3 mediated reaction of terminal alkynes and N-iodosuccinimide

Iodination of terminal alkynes using N-iodosuccinimide (NIS) in the presence of γ-Al₂O₃ was developed to afford 1-iodoalkynes with good to excellent yields (up to 99%). This described approach featured excellent chemoselectivity, good functional group tolerance, and utilization of an inexpensive catalyst.

An efficient Al₂O₃-mediated direct iodination of terminal alkynes was developed to afford 1-iodoalkynes.

1-Iodoalkynes are both highly versatile synthons in organic synthesis and valuable building blocks in materials and polymer sciences.^1,2 Traditional procedures for generating 1-iodoalkynes include iodination of metal acetylides (Scheme 1, path a),³ direct iodination of terminal alkynes (path b),⁴ iodination of propiolic acid/trialkylsilylacetylides (path c),^5,6 and a two-step homologation/iodination or elimination sequence from aldehydes or benzylic bromides (path d).^7,8 Among these achievements, path b, the preparation of 1-iodoalkynes from terminal alkynes, is highly desirable. In this regard, various iodinating conditions, including nBuLi/I₂,^4a EtMgBr/I₂,^4b I₂/DMAP,^4c NIS/AgNO₃,^4d NIS/BnN₃,^4e NIS/DBU,^4f NIS/Ag/C₃N₄,^4g KI/CuI/PhI(OAc)₂/Et₃N,^4h Me₃SiI/PhI(OAc)₂,⁴ⁱ CuI/TBAB/Et₃N,^4j TBAI/Oxone,^4k KI/TBHP,^4l TBAI/PhI(OAc)₂,^4m chloramine-B/KI,⁴ⁿ KI/Cu₂SO₄/BPDS,^4o ZnI₂/TBN,^4p NIS/[Au(AIPr)(NEt₃)][HF₂],^4q HMBMIBDCI/DBU,^4r NaI/MeOH/divided cell,^4s and N-iodomorphonine/CuI,^4t have been reported. However, some of these approaches might suffer from expensive metal catalysts, hazardous or toxic reagents, harsh reaction conditions, or generation of wastes that bring about environmental problems, thereby restricting their practical applications. Though considerable progress has been achieved, the development of efficient and environmentally benign protocols is still required.Open in a separate windowScheme 1Approaches towards to 1-iodoalkynes.It is well recognized that solids can play a vital role in developing new cleaner technologies via their capacities to serve as catalysts or support reagents and influence product selectivity, and some books have documented the applications of solids in organic synthesis.^9–11 Aluminum oxide (Al₂O₃) is an inert, odorless and white amorphous material, and has been used as catalyst in various industrial processes for many years.^12,13 But the utilization of aluminum oxide in synthetic organic chemistry especially for halogenation of aromatic compounds and alkynes is very little.^14–18 γ-Aluminum oxide is one of the three common crystal forms of aluminum oxide. Pagni and Kabalka described γ-Al₂O₃ mediated iodination of alkynes and aromatic substrates with I₂ to afford E-diiodoalkenes and iodinated aromatic compounds, respectively.¹⁴ Those iodinations did not occur without the activation of γ-Al₂O₃. N-Iodosuccinimide (NIS) is a well-known iodinating agent and widely used in organic synthesis. Iodination with N-iodosuccinimide (NIS) often needs activating reagents. However, any accompanying reagents used along with iodinating reagents should be easily available to exploit more simple and efficient iodination procedure. Inspired by the indispensable role of γ-Al₂O₃ in the iodination of alkynes and aromatic compounds,¹⁴ we envisioned that γ-Al₂O₃ could activate the N-iodosuccinimide to generate 1-iodoalkynes from terminal alkynes. Herein, we report the γ-Al₂O₃ mediated direct iodination of terminal alkynes for the synthesis of 1-iodoalkynes under mild reaction condition.As shown in †). Similarly, high yields of 1-iodoalkyne 3aa were also obtained when basic and acidic Al₂O₃ were used instead of neutral Al₂O₃ (entry 4–5). Hence, the reaction was further examined in the presence of neutral Al₂O₃. The effort to decrease the reaction temperature to 25 °C only led to low yield (entry 6). Subsequently, we probed different solvents including DMF, THF, EA, MeOH and hexane, but those solvents resulted in poor yields of desired product (entry 7–11). Moreover, the reaction was investigated by varying the amount of Al₂O₃ and NIS to enhance the performance of the reaction (†).Optimization of the reaction conditions^a

Gram-scale carbasugar synthesis via intramolecular seleno-Michael/aldol reaction

Carbasugars represent an important category of natural products possessing a broad spectrum of biological activities. Lots of effort has been done to develop gram scale synthesis. We are presenting a new approach to gram scale synthesis of the carbasugar skeleton via intramolecular seleno-Michael/aldol reaction. The proposed strategy gave gram amounts of 6-hydroxy shikimic ester in a tandem process in 36% overall yield starting from d-lyxose. We have attempted to demonstrate the synthetic utility of 6-hydroxyshikimic acid derivatives by covering the important synthetic modifications and related applications, namely synthesis of protected (−)-gabosine E, (−)-MK7606, (−)-valienamine and finally unprotected methyl (−)-shikimate.

A new approach to gram scale synthesis of carbasugar derivatives via intramolecular seleno-Michael/aldol reaction.     

New synthesis of 2-aroylbenzothiazoles via metal-free domino transformations of anilines,acetophenones, and elemental sulfur

A new synthesis of 2-aroylbenzothiazoles via iodine-promoted domino transformations of anilines, acetophenones, and elemental sulfur was demonstrated. The highlights of this tandem synthesis are (1) easily available anilines and acetophenones as feedstock; (2) transition metal-free conditions; (3) inexpensive, nontoxic, easy handling, and abundant elemental sulfur as a building block. This synthetic strategy would complement the existing methods in the synthesis of this important heterocyclic scaffold. To our best knowledge, the formation of 2-aroylbenzothiazoles from simple anilines, acetophenones, and elemental sulfur was not previously reported in the literature.

A new synthesis of 2-aroylbenzothiazoles via iodine-promoted domino transformations of anilines, acetophenones, and elemental sulfur was demonstrated.     

天七方对过氧化氢诱导心肌细胞损伤模型核因子E2相关因子2/抗氧化反应元件通路的影响

目的探讨天七方(TQ)对过氧化氢(H2O2)所致心肌细胞损伤的核因子E2相关因子2/抗氧化反应元件(Nrf2/ARE)通路的影响,阐明TQ抗心肌损伤的分子机制。方法建立H2O2诱导的心肌损伤模型,通过MTT法观察在不同浓度TQ的干预下,对心肌细胞增殖作用的影响,Western blot法检测Nrf2/ARE通路相关蛋白表达情况。结果与空白组相比,TQ对心肌细胞无明显损伤,并且TQ可减少H2O2所导致心肌细胞损伤(P0.01)。此外,TQ可上调蛋白Nrf2和HO-1的表达。结论 TQ通过激活Nrf2/ARE通路,增加蛋白HO-1的表达,抑制H2O2所致的心肌细胞的氧化损伤。     

Influence of nonspecific reaction on determination of H2O2 using Trinder reagents

BACKGROUND: We examined two enzymatic reagents for cholesterol measurement that contained cholesterol oxidase. One of the reagents gave higher values by up to 11 mg/dl in samples of 109 out of 3119 patients examined. We found that the positive errors were caused by a nonspecific reaction that has not previously been recognized in the determination of H(2)O(2) using Trinder reagents, and we further discovered its mechanism. METHODS: We compared the total cholesterol concentration in 3119 patients between the 2 reagents. By examining the characteristics of the interferrent-susceptible reagent and affected patients' samples, we identified the cause and mechanism of the influence of the nonspecific reaction. RESULTS: The existence of potassium ferrocyanide in the reagent gave rise to positive errors when the concentration of unsaturated iron binding capacity (UIBC) in the patients' sample was <70 microg/dl. Moreover, ceruloplasmin in the patients' sample was found to cause a nonspecific reaction and its influence was proportional to the serum copper concentration. The two types of reagents compared in the present study included buffers with different metal chelating capacities; the one with the lower capacity gave an erroneous measurement. The buffer in the reagent without influence had been acting as a chelating agent. Therefore, the influence of the interferrent-susceptible reagent could be prevented by addition of a chelating agent (e.g. EDTA). CONCLUSIONS: Trinder reagents containing potassium ferrocyanide have been widely used for clinical diagnostic tests such as creatinine, uric acid and so on. These reagents would have similar problems. Some test items might have a greater influence than cholesterol reagent. Physicians should be aware of the risks of diagnostic mistakes due to these errors of measurement.     

过氧化氢低温等离子体灭菌新技术

低温等离子体灭菌技术是近年来消毒灭菌领域的一种新的物理灭菌技术.随着临床医学高新技术的快速发展,现有的灭菌技术已不能满足一些不耐高温的精密医疗器械等特殊需要,如纤维窥镜和其他畏热材料都需要低温灭菌技术.低温等离子体灭菌技术是继戊二醛、环氧乙烷等灭菌技术之后的新的低温灭菌技术.     

Cu/TEMPO catalyzed dehydrogenative 1,3-dipolar cycloaddition in the synthesis of spirooxindoles as potential antidiabetic agents

A series of spiro-[indoline-3,3′-pyrrolizin/pyrrolidin]-2-ones, 4, 5 and 6 were synthesized in a sequential manner from Cu–TEMPO catalyzed dehydrogenation of alkylated ketones, 1 followed by 1,3-dipolar cycloaddition of azomethine ylides via decarboxylative condensation of isatin, 2 and l-proline/sarcosine, 3 in high regioselectivities and yields. The detailed mechanistic studies were performed to identify the reaction intermediates, which revealed that the reaction proceeds via dehydrogenative cycloaddition. Additionally, the regio and stereochemistry of the synthesized derivatives were affirmed by 2D NMR spectroscopic studies. The synthesized derivatives were explored further with molecular docking, in vitro antioxidant, and anti-diabetic activities.

A series of spiro-[indoline-3,3′-pyrrolizin/pyrrolidin]-2-ones were synthesized from Cu–TEMPO catalyzed dehydrogenation followed by 1,3-dipolar cycloaddition of azomethine ylides via decarboxylative condensation, resulting in high regioselectivities and yields.     

Cu/TCH-pr@SBA-15 nano-composite: a new organometallic catalyst for facile three-component synthesis of 4-arylidene-isoxazolidinones

A copper complex supported on SBA-15 nanoparticles (Cu/TCH-pr@SBA-15) was synthesized by the post-synthesis modification of nano-mesoporous silica with 3-chloropropyltriethoxysilane (CPTES) and thiocarbohydrazide (TCH) and subsequent metal–ligand coordination with Cu(ii). These nanocomposites were thoroughly characterized by FT-IR spectroscopy, TEM, FE-SEM, EDX, atomic absorption spectroscopy and N₂ adsorption–desorption (BET) studies. Then, a solvent-free method was developed for the three-component synthesis of 4-arylidene-isoxazolidinones via condensation of hydroxylamine hydrochloride, ethyl acetoacetate and various aromatic aldehydes using Cu/TCH-pr@SBA-15 as a highly efficient nanocatalyst. This new economic and eco-friendly methodology has remarkable advantages such as excellent yields, a shorter reaction time, an easy purification procedure, simplicity, green conditions, solvent-free conditions, and recoverability of the nanocatalyst.

A copper complex supported on SBA-15 nanoparticles (Cu/TCH-pr@SBA-15) was synthesized by the post-synthesis modification of mesoporous silica with (OEt)₃Si-(CH₂)₃Cl and thiocarbohydrazide (TCH) and subsequent metal–ligand coordination with Cu(ii).     

Copper-catalyzed one-pot domino reactions via C–H bond activation: synthesis of 3-aroylquinolines from 2-aminobenzylalcohols and propiophenones under metal–organic framework catalysis

A Cu₂(OBA)₂(BPY) metal–organic framework was utilized as a productive heterogeneous catalyst for the synthesis of 3-aroylquinolines via one-pot domino reactions of 2-aminobenzylalcohols with propiophenones. This Cu-MOF was considerably more active towards the one-pot domino reaction than a series of transition metal salts, as well as nano oxide and MOF-based catalysts. The MOF-based catalyst was reusable without a significant decline in catalytic efficiency. To the best of our knowledge, the transformation of 2-aminobenzylalcohols to 3-aroylquinolines was not previously reported in the literature, and this protocol would be complementary to previous strategies for the synthesis of these valuable heterocycles.

Cu₂(OBA)₂(BPY) metal–organic framework was utilized as a productive heterogeneous catalyst for the synthesis of 3-aroylquinolines via one-pot domino reactions of 2-aminobenzylalcohols with propiophenones.     

Hydrogen peroxide-mediated synthesis of 2,4-substituted quinazolines via one-pot three-component reactions under metal-free conditions

An efficient metal-free synthesis of 2,4-substituted quinazolines via a hydrogen peroxide-mediated one-pot three-component reaction of 2-aminoaryl ketones, aldehydes, and ammonium acetate has been developed. The transformation proceeded readily under mild conditions in the presence of commercially available hydrogen peroxide. The significant advantages of this approach are (1) the readily available atom-efficient and green hydrogen peroxide as oxidant; (2) no transition metal catalyst is required; (3) mild reaction conditions; and (4) wide substrate scope. To the best of our knowledge, utilizing hydrogen peroxide as an atom-efficient and green oxidant for the synthesis of 2,4-substituted quinazolines has not previously been reported in the literature. This method is complementary to previous protocols for the synthesis of 2,4-substituted quinazolines.

An efficient metal-free synthesis of 2,4-substituted quinazolines via a hydrogen peroxide-mediated one-pot three-component reaction of 2-aminoaryl ketones, aldehydes, and ammonium acetate has been developed.     

Substrate-controlled selectivity switch in a three-component reaction: sequential synthesis of spiro-oxazolidinedione-cyclopentenones and hydroxy enaminobarbiturates in water

An efficient eco-friendly catalyst-free three-component domino multicyclization for the synthesis of new spirobicyclic oxazolidinedione containing cyclopentenone moieties has been established by mixing amines, β-dicarbonyl compounds and N,N′-dimethylalloxan in water at room temperature. This domino process involves multiple reactions such as enamination/aldol-like reaction/Stork enamine annulation/intramolecular cyclization under mild conditions.

Spiro-oxazolidinedione-cyclopentenones and hydroxy enaminobarbiturates could be selectively formed from amines, β-dicarbonyl compounds and alloxan derivatives under catalyst-free conditions in water.     

I2/TBHP mediated domino synthesis of 2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)-N-aryl/alkyl benzamides and evaluation of their anticancer and docking studies

A novel I₂/TBHP mediated domino synthesis of 2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)-N-phenyl benzamides by reaction of isatins with o-amino N-aryl/alkyl benzamides was described. This was the first application of o-amino N-aryl/alkyl benzamides participating in oxidative rearrangement with isatins for synthesis of desired products. The synthesized compounds contained amide and quinazoline units and their combination resulted in molecular hybridization of two important pharmacophores. In this study, the synthesized compounds 3a–r were screened for cytotoxicity against four cancer cell lines A549, DU145, B16-F10, and HepG2 and also non-cancerous cell line CHO-K1. The compounds 3c, 3l and 3o gave promising results. The in silico molecular docking studies (PDB ID 1N37) also validated the anticancer activity of these compounds showing good binding affinity with target DNA and by acting as DNA intercalators.

A novel I₂/TBHP mediated domino reaction of isatins for the synthesis of 2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)-N-phenyl benzamides was described. The synthesized compounds gave promising results and were screened for cytotoxicity against cancerous cell lines.