One-pot Cascade Reaction Research Articles

Synergistic Catalysis of Brønsted Acid and Lewis Acid Coexisted on Ordered Mesoporous Resin for One-Pot Conversion of Glucose to 5-Hydroxymethylfurfural.

A novel bifunctional ordered phenolic resin with Brønsted acid and Lewis acid sites (Yb(OTf)2/PhSO3H-MPR) was prepared for the first time by a two-step sulfonation and postgrafting protocol. The Brønsted acids (benzenesulfonic acids) were transformed from the phenyl groups that existed in the skeleton of ordered mesoporous phenolic resin. Meanwhile, the benzenesulfonic acids can coordinate with Yb(OTf)3 compound, resulting in the generation of Lewis acids in the pore channels of ordered phenolic resin. Yb(OTf)2/PhSO3H-MPR sample retained large specific surface and well-ordered hexagonal mesopores. As expected, it can promote one-pot cascade reaction by using glucose as the reactant to produce 5-hydroxymethylfurfural with good conversion and moderate selectivity. This synergistic catalytic performance could be attributed to its uniformly distributed Brønsted–Lewis acids. Meanwhile, the intrinsic hydrophobic pore surface can decrease the interference of water solvent, leading to enhanced catalytic efficiency. Besides, it was reused more than five times, showing good stability in water.

Enantioselective Synthesis of Pharmaceutically Active γ-Aminobutyric Acids Using a Tailor-Made Artificial Michaelase in One-Pot Cascade Reactions.

Chiral γ-aminobutyric acid (GABA) analogues represent abundantly prescribed drugs, which are broadly applied as anticonvulsants, as antidepressants, and for the treatment of neuropathic pain. Here we report a one-pot two-step biocatalytic cascade route for synthesis of the pharmaceutically relevant enantiomers of γ-nitrobutyric acids, starting from simple precursors (acetaldehyde and nitroalkenes), using a tailor-made highly enantioselective artificial “Michaelase” (4-oxalocrotonate tautomerase mutant L8Y/M45Y/F50A), an aldehyde dehydrogenase with a broad non-natural substrate scope, and a cofactor recycling system. We also report a three-step chemoenzymatic cascade route for the efficient chemical reduction of enzymatically prepared γ-nitrobutyric acids into GABA analogues in one pot, achieving high enantiopurity (e.r. up to 99:1) and high overall yields (up to 70%). This chemoenzymatic methodology offers a step-economic alternative route to important pharmaceutically active GABA analogues, and highlights the exciting opportunities available for combining chemocatalysts, natural enzymes, and designed artificial biocatalysts in multistep syntheses.

An unexpected multi-component one-pot cascade reaction to access furanobenzodihydropyran-fused polycyclic heterocycles

An unexpected multi-component one-pot cascade reaction of hydroxyketones with ortho-hydroxychalcones has been developed to afford an array of new furanobenzopyran-fused polycyclic compounds with complex molecular architectures. This reaction not only establishes a new reaction mode of ortho-hydroxychalcones but also provides an expedient and convenient synthetic strategy to access complex furanobenzopyran-fused heterocycles.

Mesoporous polymeric catalysts with both sulfonic acid and basic amine groups for the one-pot deacetalization−Knoevenagel reaction

Acid–base bifunctional P(DVB–NH2–n-SO3H) catalysts with mesoporous structure have been prepared and characterized for a one-pot cascade reaction with good recycling properties.

Amino- and sulfo-bifunctionalized hyper-crosslinked organic nanotube frameworks as efficient catalysts for one-pot cascade reactions

The synthesis of amino- and sulfo-bifunctionalized hyper-crosslinked organic nanotube frameworks for one-pot cascade reactions was reported for the first time.

One-pot cascade ethylene oligomerization using Ni/Siral-30 and H-ZSM-5 catalysts

A study on the ethylene oligomerization was carried out using a one-pot cascade continuous flow fixed-bed reactor, loaded with Ni/Siral-30 and H-ZSM-5 catalysts at the same time. The used Siral-30 and ZSM-5 are commercial silica alumina (Sasol, SiO2/Al2O3 = 30/70) and zeolite (Zeolyst CBV 2314) materials, respectively. Compared to the catalytic results from reactions with the single catalysts under identical conditions, the one-pot cascade Ni/Siral-30 + H-ZSM-5 exhibited close to 100% conversion, resulted in a completely reversed Schulz-Flory type product distribution (C10+ > C8 > C6 > C4), and yielded the highest amount of liquid product for the entire reaction time at 250 °C (0.14 and 0.05 g gcat.−1 h−1 of a total liquid and C10+, respectively). A liquid product containing about 30% aromatic compounds, which is one of the important constituents needed for jet-fuel, was obtained from the one-pot cascade reaction. We also confirmed that the results obtained from Ni/Siral-30 + H-ZSM-5 in the gas-slurry autoclave reactor were significantly different than those obtained from the one-pot cascade reaction. The overall results demonstrate that a sequential one-pot cascade catalysis over Ni-containing and Brønsted acidic catalysts can be a good method for improving the production of jet-fuel range hydrocarbons from ethylene conversion.

Polyelectrolytes Tailored Enzyme Cascades with Enhanced Stability and Activity for One‐pot Synthesis

AbstractCascade enzymes from the same origin or different resources often differ in their pH windows of stability and activity, thus impeding one‐pot enzyme cascade reactions. Here we present a method to assemble enzyme cascades using enzyme‐polyelectrolyte as the building block, in which the polyelectrolytes not only assemble enzymatic cascades via electrostatic interactions but also create favorable microenvironments for enzymes to expand their pH windows of stability and activity. We first demonstrated the effectiveness of this method for the oxidization of p‐xylene to p‐toluic acid using chloroperoxidase (CPO) and xanthine oxidase (XO) cascade, in which CPO from Caldariomyces fumago and XO from bovine milk were covalently linked to polymethacrylic acid (PMAA) and chitosan quaternary ammonium salt, respectively. Conjugation of the enzymes with PMAA and chitosan expanded the stability and activity pH windows for CPO and XO and increased the yield of p‐toluic acid production from p‐xylene by 7.6‐fold in comparison to that obtained from their native counterparts in soluble form. We then applied this method to assemble glucose oxidase (GOx) and horseradish peroxidase (HRP) cascade. The GOx‐PMAA@HRP‐chitosan displayed a lower Km and higher apparent activity at low glucose concentration, as compared to GOx/HRP cascade in soluble form, suggesting that the assembly method boosted the outcome of the one‐pot enzyme cascade reaction.

MIL-101 supported highly active single-site metal catalysts for tricomponent coupling

Metal-organic frameworks with regular pore structures provide powerful platforms for the design of single-site metal catalysts for chemical transformation. In this paper, we develop a facile, stable and recyclable MOF-supported Cu(II) catalyst, MIL-101-SO3Cu. It shows extremely high activity for the A3 coupling of alkynes, aldehydes and amines. The turnover frequency can reach 6.8 × 105 h−1 under neat conditions, which is the highest so far reported for the reaction. The high activity is because the specific structure of the MIL-101-SO3 support enables a single-site dispersion and an unhindered open environment for the metal ion. MIL-101-SO3Cu also exhibits high activity for the one-pot cascade reactions combining A3 coupling and 5-endo-dig cyclization.

Propane to light olefins by one-pot cascade and series reactions

Propane is selectively converted to propylene via propane dehydrogenation (PDH) process for an on-purpose propylene usage. Due to regional market demands, olefin interconversion for propylene-to-ethylene (PTE) is required to control the supply-demand of light olefins. Our concern centers on combining the PDH and PTE reactions to achieve a simple catalytic process for selective production of light olefins from propane. Herein, converting propane to light olefins is investigated via cascade and series PDH-PTE reactions over highly selective two catalysts. From the catalytic results, selectively produced propylene over a PDH catalyst (Cr2O3/Al2O3) from propane was readily converted to other light olefins over a PTE catalyst (modified ZSM-5). The modified ZSM-5 as the PTE catalysts was further studied in the both cascade and series reactions with different reaction conditions in order to find an optimum reaction condition for high olefin yield and selectivity with low methane selectivity as well as to investigate the influence of process parameters on the catalytic activity. The AHFS treated ZSM-5 (AHFS-ZSM-5) as the PTE catalyst in PDH-PTE series reaction exhibited a superior light olefin yield (50.7 wt%) and olefin selectivities up to 76.7 wt% (26.9 wt% ethylene, 38.0 wt% propylene, and 11.8 wt% butenes) with low methane selectivity (4.27 wt%) at 550 °C, WHSV 7 h−1, and propylene partial pressure in the PDH model feed 0.025 MPa.

Highly Selective Palladium-Catalyzed Hydroborylative Carbocyclization of Bisallenes to Seven-Membered Rings.

A highly selective palladium-catalyzed hydroborylative carbocyclization of bisallenes to afford seven-membered rings has been established. This ring-closing coupling reaction showed good functional group compatibility with high chemo- and regioselectivity, as seven-membered ring 3 was the only product obtained. The extensive use of different linkers, including nitrogen, oxygen, malononitrile, and malonate, showed a broad substrate scope for this approach. A one-pot cascade reaction was realized by trapping the primary allylboron compound with an aldehyde, affording a diastereomerically pure alcohol and a quaternary carbon center by formation of a new C-C bond. A comprehensive mechanistic DFT investigation is also presented. The calculations suggest that the reaction proceeds via a concerted hydropalladation pathway from a Pd(0)-olefin complex rather than via a pathway involving a defined palladium hydride species. The reaction was significantly accelerated by the coordination of the pendant olefin, as well as the introduction of suitable substituents in the bridge, due to the Thorpe-Ingold effect.

Janus N-Doped Carbon@Silica Hollow Spheres as Multifunctional Amphiphilic Nanoreactors for Base-Free Aerobic Oxidation of Alcohols in Water

The hydrophobicity/hydrophilicity of nanocatalysts has a significant impact on their performances via modulating the adsorption, transfer, and desorption of reactants/products. In this work, we reported a novel multifunctional amphiphilic nanoreactor composed of Janus nitrogen-doped carbon@silica hollow nanostructure and ultrasmall Pt nanoparticles. The core/shell polybenzoxazine@mesosilica spheres were used as the precursor for pyrolysis. It was found that the internal polybenzoxazine was decomposed from interior to exterior and transformed into a nitrogen-doped carbon hollow shell that partly embedded into the mesosilica layer, forming the Janus hollow spheres. The obtained nanoreactor showed remarkable activity and selectivity for base-free aerobic oxidation of alcohols in water using air as the oxidant. A one-pot oxidation-condensation cascade reaction was also successfully demonstrated to synthesize imines from alcohols and amines with good yields. The sorption analyses revealed that the superior hydrophilicity/hydrophobicity strengthened both adsorption of hydrophobic alcohols from water and desorption of byproduct water molecules from the active sites. The doped nitrogen atoms in the carbon matrix were used not only as anchoring sites for stabilizing ultrasmall Pt nanoparticles but also as basic active sites for accelerating the deprotonation process. Moreover, due to the anchoring effect of nitrogen and the extremely stable amphiphilicity, this nanoreactor exhibited excellent catalytic stability.

Convenient Colorimetric Detection of Cholesterol Using Multi-Enzyme Co-Incorporated Organic-Inorganic Hybrid Nanoflowers.

We have developed a microscale well-plate colorimetric assay for the multiplexed detection of cholesterol in clinical human blood samples. This system utilizes a novel multi-enzyme incorporated organic-inorganic hybrid nanoflower which entrap both cholesterol oxidase (ChOx) and horseradish peroxidase (HRP) as the organic components with copper phosphate as the inorganic component to detect cholesterol levels in blood samples. The hybrid nanoflowers, synthesized via an extremely simple but rapid sonication-mediated method within 5 min at room temperature, enable an efficient one-pot two-enzyme cascade reaction. The ChOx in the nanoflowers catalyze the generation of H2O2 only in the presence of cholesterol in the sample. This subsequently activates the HRP co-entrapped in the nanoflowers, thereby leading to the conversion of the employed chromogenic substrate, 3,3',5,5'-tetramethylbenzidine (TMB), into a blue-colored product. This strategy can be used to detect target cholesterol concentrations as low as 8 μM, with a linear range from 10 to 70 μM, which is suitable to diagnose high levels of cholesterol (hypercholesterolemia) with excellent stability over three weeks at room temperature. The biosensor also exhibited an excellent selectivity to detect target cholesterol even in the presence of common interfering biomolecules in human blood and showed a high degree of precision when employing human blood serum samples. Therefore, this hybrid nanoflower-based assay can be used in clinical practice for the multiplexed and reliable quantification of cholesterol, and readily extended to other enzymes to prepare multi-step cascade enzymatic reactions for various biotechnological applications.

One-pot sequential double annulations cascade reaction for imidazo[1,2-b]pyrazoles synthesis

We have developed efficient and green methods for the synthesis of imidazo[1,2-b]pyrazole derivatives by Groebke–Blackburn–Bienayme (GBB) reaction of 5-aminopyrazole, aldehyde and trimethylsilyl cyanid under thermal condition in 1-n-butyl-3-methylimidazolium tetrafluoroborate [Bmim]BF4 ionic liquid. A one-pot sequential double annulation cascade reaction has also been demonstrated for imidazo[1,2-b]pyrazoles synthesis.

A Dual-Functional Catalyst for Cascade Meerwein-Pondorf-Verley Reduction and Dehydration of 4'-Methoxypropiophenone to Anethole.

Anethole is an ingredient in many flavours, fragrances and pharmaceutical formulations. To reduce the dependence of its supply on natural oils, a green route for anethole synthesis was designed on the basis of Meerwein-Pondorf-Verley (MPV) reduction and dehydration of 4'-methoxypropiophenone. The one-pot cascade reactions were heterogeneously catalysed by dual-functional Zr-MSU-3, a predominantly Lewis-acidic catalyst with a Si/Zr ratio of 10 and pores with sizes in the range of 3.2-4.2 nm. The use of 2-pentanol as solvent and hydrogen donor for the MPV reduction was advantageous, as its high boiling point enhances the rate of the reactions, especially the dehydration of the MPV product, 1-(4-methoxyphenyl)-propan-1-ol. This dispenses with the need for a strong acid catalyst that could result in by-products of acid-catalysed reactions. Anethole yields of 91 % with a trans/cis isomer ratio of about 92:8, similar to that of natural anethole, were obtained. In comparison, microporous Zr-beta (Si/Zr 12.5) gave lower activity owing to pore-size constraints. Hence, through design of the reactions and catalyst, 4'-methoxypropiophenone can be efficiently converted to anethole in a sustainable and green manner.

Double role of metalloporphyrins in catalytic bioinspired supramolecular metal-organic frameworks (SMOFs).

Heterogeneous catalysts are of great interest in many industrial processes for environmental reasons and, during recent years, a great effort has been devoted to obtain metal-organic frameworks (MOFs) with improved catalytic behaviour. Few supramolecular metal-organic frameworks (SMOFs) are stable under ambient conditions and those with anchored catalysts exhibit favourable properties. However, this paper presents an innovative approach that consists of using metal nodes as both structural synthons and catalysts. Regarding the latter, metalloporphyrins are suitable candidates to play both roles simultaneously. In fact, there are a number of papers that report coordination compounds based on metalloporphyrins exhibiting these features. Thus, the aim of this bioinspired work was to obtain stable SMOFs (at room temperature) based on metallo-porphyrins and explore their catalytic activity. This work reports the environmentally friendly microwave-assisted synthesis and characterization of the compound [H(bipy)]2[(MnTPPS)(H2O)2]·2bipy·14H2O (TPPS = meso-tetra-phenyl-porphine-4,4',4'',4'''-tetra-sulfonic acid and bipy = 4,4'-bi-pyridine). This compound is the first example of an MnTPPS-based SMOF, as far as we are aware, and has been structurally and thermally characterized through single-crystal X-ray diffraction, IR spectroscopy, thermogravimetry and transmission electron microscopy. Additionally, this work explores not only the catalytic activity of this compound but also of the compounds μ-O-[FeTCPP]2·16DMF and [CoTPPS0.5(bipy)(H2O)2]·6H2O. The structural features of these supra-molecular materials, with accessible networks and high thermal stability, are responsible for their excellent behaviour as heterogeneous catalysts for different oxidation, condensation (aldol and Knoevenagel) and one-pot cascade reactions.

One-pot hydrogen production and cascade reaction of furfural to bioproducts over bimetallic Pd-Ni TUD-1 type mesoporous catalysts

Bimetallic Pd-Ni TUD-1 type mesoporous catalysts are effective for the cascade reaction of the renewable platform chemical furfural (FUR) to the useful bioproducts 2-alkoxyfuran, 2-methylfuran (2MF), 4-oxopentanal and its acetals, which find diverse applications, some already in the market. With a single catalyst, the in situ hydrogen supply from formic acid (FAc), as well as several acid-reduction steps of the overall catalytic process were triggered, leading to the desired bioproducts (bioPs), all in one-pot under moderate reaction conditions. These multipurpose materials were prepared using different procedures and conditions, which influenced the material properties and the catalytic performances. Detailed characterisation (microstructural/molecular level) and catalytic studies led to new mechanistic insights into the FUR reaction (with identification of intermediates), allowed to assess the roles of the different types of metal species in the complex reaction mechanism, understand the influence of material properties on the catalytic process, and catalyst stability and regeneration. The best-performing catalyst was prepared stepwise via impregnation of palladium on a hydrothermally synthesised nickel silicate with a molar ratio Si/Ni of 20, ending with filtration-washing-calcination procedures. This catalyst led to 83% 2MF yield, at 98% FUR conversion (90% total bioPs yield), using 1-butanol as solvent, at 170 °C. The reported catalytic protocol benefits from the fact that external usage of H2 for catalyst activation and/or the catalytic reaction is not required, no high-pressure gases are used, and FAc is used as source of hydrogen supplied in situ for the catalytic reaction under moderate conditions. Moreover, FAc presents low toxicity, it is easy to handle/store, and is a typical coproduct of carbohydrate biomass conversion processes, and thus its repurposing is highly desirable.

Synthesis of Fused Purine Heterocycles via a One-pot Cascade Reaction of a Trisubstituted Pyrimidine

A rapid and expedient one-pot procedure for the synthesis of fused purine derivatives from a trisubstituted pyrimidine and various amines has been developed. The tandem substitution reaction and copper(I)-catalyzed annulation exhibited high efficiency. The fused heterocyclic products contain the purine scaffold and may be useful in medicinal chemistry and bioscience.

Functionalized Spiroindolines with Anticancer Activity through a Metal-Free Post-Ugi Diastereoselective One-Pot Cascade Reaction.

A post-Ugi diastereoselective one-pot cascade reaction requiring no metal catalyst was developed. The reaction scope was wide with mild conditions and good yields. A collection of spiroindolines was prepared by the protocol and screening tests in several difficult-to-inhibit cancer cell lines were conducted. The relationship of structure and anticancer activities was promising and in the Huh7 cell lines compound 16 j is more potent than Vinbalstine. The cyclization design strategy could be applicable to other multicomponent reactions (MCRs) for synthesizing bioactive and drug-like heterocycles.

Photo‐biocatalytic One‐Pot Cascades for the Enantioselective Synthesis of 1,3‐Mercaptoalkanol Volatile Sulfur Compounds

The synthesis of enantiomerically pure 1,3-mercaptoalkanol volatile sulfur compounds through a one-pot photo-biocatalytic cascade reaction is described. Two new KRED biocatalysts with opposite enantioselectivity were discovered and proved to be efficient on a wide range of substrates. The one-pot cascade reaction combining photocatalytic thio-Michael addition with biocatalytic ketoreduction in an aqueous medium provides a green and sustainable approach to enantiomerically pure 1,3-mercaptoalkanols in high yields with excellent enantioselectivity.

Tunable Synthesis of Functionalized Cyclohexa-1,3-dienes and 2-Aminobenzophenones/Benzoate from the Cascade Reactions of Allenic Ketones/Allenoate with Amines and Enones.

A TEMPO-dependent tunable synthesis of functionalized cyclohexa-1,3-dienes and 2-aminobenzophenones/benzoate from the one-pot cascade reactions of allenic ketones/allenoate with amines and enones is presented. Mechanistically, the construction of the entitled six-membered carbocycles involves the in situ generation of an enaminone intermediate via the conjugate addition of allenic ketone with amine followed by its catalyst- and base-free [3+3] annulation with enone along with the simultaneous introduction of the valuable amino and carbonyl groups.