Henry Reaction Research Articles

Efficient Catalyst-Free Henry Reaction between Nitroalkanes and Aldehydes or Trifluoromethyl Ketones Promoted by Tap Water

AbstractThe first examples of highly effective Henry reactions between nitroalkanes and aldehydes or trifluoromethyl ketones that proceed under catalyst-free and additive-free conditions, in a recyclable tap water medium, and at room temperature are reported. This process tolerates a broad range of aldehydes and trifluoromethyl ketones to give a series of β-nitro alcohol products in excellent yields. Such products are widely used in the syntheses of pharmaceutical intermediates and natural products. This protocol can be successfully scaled up to a 50-mmol scale without a reduction in yield. Tap water from different locations in China exhibited pH values ranging from 7.5 to 8.1, but the varying pH had no effect on the yield and the processes were successfully reproduced. Finally, the tap water was effectively recovered and reused without any postprocessing, even when the reaction substrates were different.

A Novel Organometallic Coordination Polymer as a Heterogeneous Catalyst for C−C Bond Formation

One-pot solvothermal reaction of Ni(II) salt with 2-aminopyridine and thiethyl orthoformate in methanol afforded a novel one-dimensional nickel coordination polymer which can be regarded as a potential heterogeneous catalyst for nitroaldol (Henry) reaction.

Polymerization, Stimuli-induced Depolymerization, and Precipitation-driven Macrocyclization in a Nitroaldol Reaction System.

Dynamic covalent polymers of different topology have been synthesized from an aromatic dialdehyde and α,ω-dinitroalkanes via the nitroaldol reaction. All dinitroalkanes yielded dynamers with the dialdehyde, where the length of the dinitroalkane chain played a vital role in determining the structure of the final products. For longer dinitroalkanes, linear dynamers were produced, where the degree of polymerization reached a plateau at higher feed concentrations. In the reactions involving 1,4-dinitrobutane and 1,5-dinitropentane, specific macrocycles were formed through depolymerization of the linear chains, further driven by precipitation. At lower temperature, the same systemic self-sorting effect was also observed for the 1,6-dinitrohexane-based dynamers. Moreover, the dynamers showed a clear adaptive behavior, displaying depolymerization and rearrangement of the dynamer chains in response to alternative building blocks as external stimuli.

Binaphthyl-Proline Hybrid Chiral Ligands: Modular Design, Synthesis, and Enantioswitching in Cu(II)-Catalyzed Enantioselective Henry Reactions.

Chiral O-N-N tridentate ligands were designed from proline and BINOL. Their design strategy and performance were evaluated using a copper(II)-catalyzed asymmetric Henry reaction as a model. The desired β-nitroalcohols were obtained in up to 94% ee's. Preliminary results suggested that the stereofacial selection of the reactions was mainly controlled by the chiral diamine moiety derived from proline, and matching of the central and axial chiralities was essential for the high stereoselectivity of the reaction. Enantioswitching was observed when an appropriate substituent was introduced to the binaphthyl group. Si-selections were found in reactions using 2a without 3-substituents as chiral ligand, and Re-selections were found with the same high enantioselectivities when 2i bearing the 3-trifluoromethyl group was used as the chiral ligand.

Chitosan Capped Copper Oxide Nanocomposite: Efficient, Recyclable, Heterogeneous Base Catalyst for Synthesis of Nitroolefins

In this article, chitosan copper oxide nanocomposite was synthesized by the solution casting method under microwave irradiation. The nanocomposite solution was microwave irradiated at 300 watt for 3 min under optimal irradiation conditions. By suppressing particle agglomeration, the chitosan matrix was successfully used as a metal oxide stabilizer. The goal of this research was to create, characterize, and test the catalytic potency of these hybrid nanocomposites in a number of well-known organic processes. The prepared CS-CuO nanocomposites were analyzed by different techniques, including Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and field emission scanning electron microscopy (FESEM). Moreover, energy-dispersive X-ray spectroscopy (EDS) was used to measure the copper content in the prepared nanocomposite film. The finger-print peaks in the FTIR spectrum at around 632–502 cm−1 confirmed the existence of the CuO phase. The CS-CuO nanocomposite has been shown to be an efficient base promoter for nitroolefin synthesis via the nitroaldol reaction (Henry reaction) in high yields. The reaction variables were studied to improve the catalytic approach. Higher reaction yields, shorter reaction times, and milder reaction conditions are all advantages of the technique, as is the catalyst’s reusability for several uses.

Preparation of a Dual-Functionalized Acid-Base Macroporous Polymer via High Internal Phase Emulsion Templating as a Reusable Catalyst for One-Pot Deacetalization-Henry Reaction.

A macroporous dual-functional acid–base covalent organic polymer catalyst poly(St-VBC)-NH2-SO3H was prepared using high internal phase emulsion polymerization using vinylbenzyl chloride (VBC), styrene (St), and divinylbenzene (DVB) as substrates toluene as a porogenic solvent, and subsequent modification with ethylenediamine and 1,3-propane sultone. The role of various amounts of toluene as the porogenic solvent as well as the amount of 1,3-propane sultone (different ratio of acid/base sites) on the structure of the prepared materials have been carefully investigated. The prepared materials were characterized by Fourier transform infrared (FT-IR), CHNS elemental analysis, energy-dispersive X-ray (EDX), elemental mapping, field emission scanning electron microscopy (FE-SEM), and thermalgravimetric analysis (TGA). The catalytic activity of the poly(St-VBC)-NH2-SO3H series with different acid/base densities was assessed for one-pot cascade C–C bond-forming reactions involving deacetylation–Henry reactions. The poly(St-VBC)-NH2-SO3H(20) sample bearing 1.82 mmol/g of N (base site) and 1.16 mmol/g (acid site) showed the best catalytic activity. The catalyst demonstrated superior activity compared to the homogeneous catalysts, poly(St-DVB)-SO3H+EDA, poly(St-VBC)-NH2+chlorosulfonic acid, and poly(St-DVB)-SO3H+poly(St-VBC)-NH2 as the catalyst system. The optimized catalyst showed excellent catalytic performance with 100% substrate conversion and 100% yield of the final product in the one-pot production of β-nitrostyrene from benzaldehyde dimethyl acetal under cascade reactions comprising acid-catalyzed deacetalization and base-catalyzed Henry reactions. It was shown that these catalysts were reusable for up to four consecutive runs with a very slight loss of activity. The excellent performance of the catalyst was attributed to the excellent chemical and physical properties of the developed support since it provides an elegant route for preparing site-isolated acid–base dual heterogenized functional groups and preventing their deactivation via chemical neutralization.

Total Synthesis of Marine Alkaloids Cystodytins A-K.

The total synthesis of marine alkaloids cystodytins A-K has been accomplished in five to six steps starting from commercially available compounds. The highlights of the synthesis include an oxidative amination-cyclization of tryptamine and para-hydroquinones to build a tetracyclic pyridoacridinone ring with different side chains and a copper(II)-catalyzed enantioselective Henry reaction to construct an oxygenated stereogenic carbon center. For the first time, the absolute configuration of the stereogenic centers embedded in cystodytins D-I and K was established as R. Moreover, the stereochemistry of the olefin unit in the side chain of cystodytins H and I was revised to the Z configuration from the originally assigned E configuration.

Dihydrooxazine Byproduct of a McMurry–Melton Reaction en Route to a Synthetic Bacteriochlorin

A synthetic route to gem-dimethyl-substituted bacteriochlorins—models of native bacteriochlorophylls—relies on the formation of a dihydrodipyrrin precursor via a series of established reactions: van Leusen pyrrole formation, Vilsmeier formylation, Henry reaction, borohydride reduction, Michael addition, and McMurry–Melton pyrroline formation. The latter is the least known of the series. Here, the McMurry–Melton reaction of a 2-(6-oxo-2-nitrohexyl)pyrrole in the presence of TiCl3 and an ammonium acetate buffer formed the expected Δ1-pyrroline, as well as an unexpected polar, cyclic byproduct (a 5,6-dihydro-4H-1,2-oxazin-6-ol), each attached to the 2-methylpyrrole unit. Both species were characterized by single-crystal X-ray diffraction. The McMurry–Melton reaction is a type of intercepted Nef reaction (the transformation of a nitroalkyl motif into a carbonyl group), where both the Δ1-pyrroline and the dihydrooxazine derive from the reaction of the nitrogen derived from the nitro group upon complete or partial reductive deoxygenation, respectively, with the γ-keto group. The report also considers competing Nef and McMurry–Melton reactions, the nature of available TiCl3 reagents, and the use of ammonium acetate for buffering the TiCl3/HCl reagent.

Coordination Polymers from Biphenyl-Dicarboxylate Linkers: Synthesis, Structural Diversity, Interpenetration, and Catalytic Properties.

The present work explores two biphenyl-dicarboxylate linkers, 3,3'-dihydroxy-(1,1'-biphenyl)-4,4'-dicarboxylic (H4L1) and 4,4'-dihydroxy-(1,1'-biphenyl)-3,3'-dicarboxylic (H4L2) acids, in hydrothermal generation of nine new compounds formulated as [Co2(μ2-H2L1)2(phen)2(H2O)4] (1), [Mn2(μ4-H2L1)2(phen)2]n·4nH2O (2), [Zn(μ2-H2L1)(2,2'-bipy)(H2O)]n (3), [Cd(μ2-H2L1) (2,2'-bipy)(H2O)]n (4), [Mn2(μ2-H2L1)(μ4-H2L1)(μ2-4,4'-bipy)2]n·4nH2O (5), [Zn(μ2-H2L1)(μ2-4,4'-bipy)]n (6), [Zn(μ2-H2L2)(phen)]n (7), [Cd(μ3-H2L2)(phen)]n (8), and [Cu(μ2-H2L2) (μ2-4,4'-bipy)(H2O)]n (9). These coordination polymers (CPs) were generated by reacting a metal(II) chloride, a H4L1 or H4L2 linker, and a crystallization mediator such as 2,2'-bipy (2,2'-bipyridine), 4,4'-bipy (4,4'-bipyridine), or phen (1,10-phenanthroline). The structural types of 1-9 range from molecular dimers (1) to one-dimensional (3, 4, 7) and two-dimensional (8, 9) CPs as well as three-dimensional metal-organic frameworks (2, 5, 6). Their structural, topological, and interpenetration features were underlined, including an identification of unique two- and fivefold 3D + 3D interpenetrated nets in 5 and 6. Phase purity, thermal and luminescence behavior, as well as catalytic activity of the synthesized products were investigated. Particularly, a Zn(II)-based CP 3 acts as an effective and recyclable heterogeneous catalyst for Henry reaction between a model substrate (4-nitrobenzaldehyde) and nitroethane to give β-nitro alcohol products. For this reaction, various parameters were optimized, followed by the investigation of the substrate scope. By reporting nine new compounds and their structural traits and functional properties, the present work further outspreads a family of CPs constructed from the biphenyl-dicarboxylate H4L1 and H4L2 linkers.

Basified Graphene Oxide and PPO Composite Aerogel with Basified Graphene Oxide for Henry Reaction in Solvent-Free Conditions: A Green Approach

Novel basified graphene oxide and high-porosity monolithic composite aerogels of poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) containing basified graphene oxide (b-eGO) have been prepared as recoverable and reusable catalysts for the Henry reaction in solvent-free conditions at room temperature. The results showed that, although b-eGO was able to promote the reaction, it suffered from reduced stability. On the other hand, PPO/b-eGO aerogels were able to efficiently promote the Henry reaction in solvent-free conditions. The product could be obtained pure without a purification step, and the catalyst was stable for over 15 months and could be easily recycled without losing catalytic efficiency. The stereochemical outcome was further investigated in the presence of PPO/b-eGO. Despite its negligible influence on diastereoselectivity, better efficiency and a sensible reduction of reaction time were observed.

Porous aromatic frameworks containing binaphthyl-dihydroazepine units (cBAPAFs) as catalytic supports for asymmetric reactions

We present the successfully synthesis of a series of chiral polymeric aromatic frameworks containing novel enantiopure atropoisomeric 1,1′-binaphthyl-dihydroazepine-based compounds as structural building units named cBAPAFs. Three porous materials with amino, pyridinic and amino-alcohol functionalities were successfully obtained from dibrominated monomers by Suzuki-Miyaura couplings. New porous materials present surface areas up to 619 m2 g−1 determined by Brunauer–Emmett–Teller (BET), and high thermal stability. The use of nitrogen-based structural units provides useful functional groups to allow a robust binding site for metal complexes. Thus, after post-synthetic metalation with Cu(OAc)2, these materials have been applied as efficient heterogenized catalysts for the nitroaldol (Henry) reaction and a multicomponent reaction, affording chiral products with comparable enantioselectivity to that of the homogeneous system. The materials were also tested as organocatalysts for the asymmetric addition of diethylzinc to benzaldehyde and the reaction between nitro-styrene and nitroethane. These cBAPAFs could be recycled for the asymmetric nitroaldol reaction for at least 5 cycles without a significant loss in its catalytic efficiency.

Synthesis of Pd-stabilized chiral conjugated microporous polymer composites as high efficiency heterogeneous asymmetric Henry reaction catalysts

Chiral conjugated microporous polymers (CCMPs) containing amide groups were designed and synthesized by Sonogashira coupling polymerization. CCMPs are reported for the first time as heterogeneous asymmetric catalyst platforms for the stabilization of Pd with applications in asymmetric catalytic synthesis. Four Pd/CCMPs heterogeneous catalysts exhibited efficient catalytic activity (of up to 87% yield) and excellent enantioselectivity (of up to 97% enantiomeric excess value) in the asymmetric Henry reaction, with a wide range of substrates and easy recovery. The Pd/CCMPs composites could be easily recycled and maintained catalytic activity after 3 cycles of reactions. A rational catalytic cycle was proposed to further understand the role of Pd/CCMPs in the Henry reaction. This study greatly extends the application of CCMPs in heterogeneous asymmetric catalysis.

Enantioselective Henry Reaction Catalyzed by Chiral Piperazine Derivatives.

A series of novel tridentate Schiff bases is synthesized from piperazine-amine and substituted salicylaldehydes, and characterized by spectroscopic methods. These chiral ligands were used to catalyze the addition of nitromethane to various aldehydes in the presence of Cu(II) ions under ambient conditions in good yields (98%) and high enantioselectivities (9:91 er).

Porous Silica Support for Immobilizing Chiral Metal Catalyst: Unravelling the Activity of Catalyst on Asymmetric Organic Transformations

AbstractThe role of chiral metal catalysts in asymmetric reactions has developed a new forte for researchers worldwide to boost chiral synthesis in various sectors. By controlling specific interactions among chiral ligands, metal catalysts and the support material, one can design a more selective and efficient chiral heterogeneous catalytic system. Silica has been extensively used as support material in various heterogeneous systems due to its activity, stability, better recovery, and recyclability. This review details recent advances in preparation of the silica suppported chiral catalysts and their applications for various chiral transformatios such as Aldol reaction, Henry reaction, transfer hydrogenation, epoxidation, Passerini reaction etc. The review also covers different mechanisms of immobilization viz., adsorption, electrostatic and covalent interactions. The interaction mechanism of chiral metal catalyst with silica support and factors like matrix pore size and ligand confinement that influence the catalytic performance of enantioselective transformations have also been discussed.

Synthesis of Amino-Acid-Based Nitroalkenes

Fatty-acid-based nitroalkenes have recently received great attention because of their bioactivities. On the contrary, peptide- or amino-acid-based nitroalkenes have been scarcely explored so far, although they may exhibit interesting biological properties, for example, as enzyme inhibitors. In this work, we study protocols for the efficient synthesis of nitroalkenes based on natural amino acids. A variety of N-protected amino alcohols and Weinreb amides, derived from α-amino acids, were converted to the corresponding N-protected amino aldehydes, and, through a Henry reaction with nitroalkanes, produced the corresponding nitro alcohols. The subsequent elimination reaction led to the (E)-isomer of amino-acid-based nitroalkenes in moderate to high yields.

Conformationally locked cis-1,2-diaminocyclohexane-based chiral ligands for asymmetric catalysis

An efficient synthesis for a new conformationally locked chiral cis-1,2-diaminocyclohexane scaffold has been developed. The conformational lock allows for convenient symmetrical derivatization of the amino groups through the reductive amination strategy. A series of optically pure chiral ligands based on the cis-DACH scaffold has been generated to demonstrate a proof-of-concept for these ligands as chiral catalysts in the asymmetric Henry reaction. Excellent yields with moderate enantioselectivity were demonstrated at room temperature, with an increase in enantioselectivity at lower temperatures, showing the potential of this new type of cis-DACH ligand.

Aqueous synthesis of 2-aryl-3-nitro-2H[sbnd]chromenes via l-prolinamide mediated tandem oxa-Michael Henry reactions

An efficient and aqueous protocol has been developed for the synthesis of 2-aryl-3-nitro-2H-chromene derivatives. This protocol involves the l-prolinamide mediated tandem oxa-Michael Henry reaction between a variety of β-nitrostyrenes and salicylaldehyde. Among the screened solvents, the catalytic efficiency of prolinamides was found to be high in chloroform, but the best results were obtained in water to provide the 2-phenyl-3-nitro-2H-chromene in excellent yields. Substrate scope was also investigated using various substituted β-Nitrostyrenes. All reactions worked well to provide the corresponding products in very high yields. Theoretical calculations were performed to find out the reaction pathways and nature of transition state at 3–21G* basis set and TS1 corresponding to the product (S)-3a, was found favorable by 1.13 kcal/mol over TS2 corresponding to the product (R)-3a.

Asymmetric Henry reaction using a double fluorous-tagged Co–salen complex

A highly stereoselective asymmetric Henry reaction using a double fluorous-tagged Co–salen complex was conducted. The introduction of two fluorous tags into the Co–salen complex was found to be more effective in terms of improving stereoselectivity than the introduction of a strong electron-withdrawing nitro group into the same position of the salen ligand. The observed stereoselectivity was significantly higher than that when using a Jacobsen-type Co–salen complex bearing the same asymmetric source.

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban.

The human drugs – the antibiotic linezolid (1) and the anticoagulant rivaroxaban (2) – belong among modern pharmaceutics, which contain an oxazolidine-2-one moiety bearing a stereogenic center. The chirality of these drugs is a fundamental attribute for their biological activity. Herein, one of the efficient asymmetric syntheses of these drugs was studied in detail. Highly enantioselective catalysts were tested in the key step of the synthetic procedure, i.e., the asymmetric Henry reaction, under different reaction conditions, using several starting aldehydes. The corresponding nitroaldols as chiral intermediates in the syntheses of these drugs were obtained in high yields and enantiomeric excesses of up to 91% ee.

Correction to: In3+ doped magnesium ferrite an efficient magnetic catalyst for the synthesis of functionalized quinazolinone and Henry reaction

Correction to: In3+ doped magnesium ferrite an efficient magnetic catalyst for the synthesis of functionalized quinazolinone and Henry reaction