Β-amino Alcohols Research Articles

Rh(III)-catalyzed Intra- and Intermolecular 3,4-Difunctionalization of 1,3-Dienes via Rh(III)-π-allyl Amidation with 1,4,2-Dioxazolones.

We herein report a modular strategy, which enables Rh(III)-catalyzed diastereoselective 3,4-amino oxygenation and diamination of 1,3-dienes using different O- and N-nucleophiles in combination with readily available 3-substituted 1,4,2-dioxazolones (78 examples, 37-91% yield). Previous attempts to functionalize the internal double bond rested on the use of plain alcoholic solvents as nucleophilic coupling partners thus dramatically limiting the scope of this transformation. We have now identified hexafluoroisopropanol as a non-nucleophilic solvent which allows the use of diverse nucleophiles and greatly expands the scope, including an unprecedented amino hydroxylation to selectively install valuable, unprotected β-amino alcohols across 1,3-dienes. Moreover, various elaborate alcohols prove to be compatible providing unique access to complex organic molecules. Finally, this method is employed in a series of intramolecular reactions to deliver valuable nitrogen heterocycles as well as γ- and δ-lactones.

Simple approach for the synthesis of a 1,1'-(ethane-1,2 diylbis(azanediyl))bis(pentan-2-ol): 13C/1H NMR spectroscopy and electrical characterizations

1,1'-(Ethane-1,2-diylbis(azanediyl))bis(pentan-2-ol) a β-aminoalcohol material denoted as 2a has been successfully synthesized. A white highly pure transparent material has been obtained after purification by chromatography techniques. Infrared spectroscopy has been used to identify the −NH and −OH functional groups. 1 H and 13 C NMR spectroscopy has confirmed the proposed structure. Complex Impedance Spectroscopy indicates an insulator behavior of the studied materials in the 313-393°C temperature range. Conductivity within this material is in intragrain contribution and its activation energy is about 1.3 eV. The physical properties of the studied material allow to consider β-amino alcohols as versatile intermediates for many organic compounds in the making of natural and synthetic originated biologically active compounds. They are widely used as β-blockers, insecticidal agents, and chiral auxiliaries.

Pd(II)-Catalyzed Aminoacetoxylation of Alkenes Via Tether Formation.

A Pd-catalyzed method based on the use of a molecular tether is described for olefin difunctionalization. Enabled by an easily introduced trifluoroacetaldehyde-derived tether, a simultaneous introduction of oxygen and nitrogen heteroatoms across unsaturated carbon–carbon bonds was achieved under oxidative conditions, most probably via high-valent Pd intermediates. Good yields and high diastereoselectivity were obtained with aryl-substituted alkenes, whereas nonterminal alkyl-substituted olefins gave aza-Heck products. Tether cleavage under mild conditions provided fast access to functionalized β-amino alcohols.

Asymmetric Transfer Hydrogenative Amination of Benzylic Ketones Catalyzed by Cp*Ir(III) Complexes Bearing a Chiral N-(2-Picolyl)sulfonamidato Ligand

A convenient asymmetric reductive amination of benzylic ketones (α-arylated ketones) catalyzed by newly designed Cp*Ir complexes bearing a chiral N-(2-picolyl)sulfonamidato ligand was developed. Using readily available β-amino alcohols as chiral aminating agents, a range of benzo-fused and acyclic ketones were successfully reduced with formic acid in methanol at 40 °C to afford amines with favorable chemo- and diastereoselectivities. The amino alcohol-derived chiral auxiliary was easily removed by mild periodic oxidants, leading to optically active primary β-arylamines without erosion of the optical purity (up to 97% ee). The excellent catalytic performance was retained even upon lowering the amount of catalyst to a substrate/catalyst (S/C) ratio of 20,000, and the amination could be performed on a large scale exceeding 100 g. The precise hydride transfer to iminium species generated from the ketonic substrate and the chiral amine counterpart was suggested by the mechanistic studies on stoichiometric reactions of isolable hydridoiridium complexes and model intermediates such as N,O-acetal, enamine, and iminium compounds.

Enantioselective Aldol Reaction between Isatins and Ketones, Catalyzed by Chiral Norephedrine-Derived β-Amino Alcohols with a Thiophene Moiety

Enantioselective Aldol Reaction between Isatins and Ketones, Catalyzed by Chiral Norephedrine-Derived β-Amino Alcohols with a Thiophene Moiety

Brønsted Acid‐Catalysed Epoxide Ring‐Opening Using Amine Nucleophiles: A Facile Access to β‐Amino Alcohols

A mild, efficient, and metal-free synthetic protocol for the synthesis of β-amino alcohols is reported. The reaction proceeds at room temperature with only 0.5 mol % catalyst loading and affords β-amino alcohol derivatives in excellent yield. This protocol is well-tolerated by a wide range of styrene oxide and aniline derivatives. A notably efficacious gram-scale synthesis is also reported with a high TON=842. Further, the Hammett correlation study was also performed to identify the rate-determining step.

Synthesis and characterization of mononuclear Zn complex, immobilized on ordered mesoporous silica and their tunable catalytic properties

In this work, mononuclear zinc complex, [Zn(dmp)Cl2] (dmp = Neocuprine) was synthesized and characterized by quantum mechanical (QM) calculations using Density Functional Theory (DFT) and Time-dependent Density Functional Theory (TD-DFT) method. The UV–Vis absorption spectra of the molecule were calculated using the TD-DFT method at B3LYP functional and mix basis set (LANL2DZ and 6–31G(d)). The electronic transitions and their corresponding HOMOs and LUMOs were analysed. The characteristics such as chemical potential (μ), hardness value (Ƞ), softness (S), electronegativity (χ) and electrophilicity index (ω) were calculated from the HOMO-LUMO energy gap. After thorough characterization the Zn complex was incorporated to the sulfopropylsilylated ordered mesoporous silica materials via post-synthesis modification. The synthesized catalysts were characterized by powder XRD, BET, FT-IR, SEM, TGA, NMR, ICP etc., to confirm the structural integrity, presence of additional functionality, morphology of the materials and other vital parameters. After thorough characterization, all the materials were used in epoxide ring opening reaction with different amines to produce important intermediates β-amino alcohols. Gradual enhancement of catalytic activities in terms of conversion was observed from blank (without catalyst) to sulfopropylsilylated mesoporous material and finally to immobilized Zn complex incorporated hybrid ordered mesoporous materials. Zn complex incorporated MCM-48 was found to be most active in this reaction system and gave maximum 99%, 92% and 70% conversion of piperidine, morpholine and aniline respectively and 98% selectivity of the desired products.

Design, synthesis, and bioactivity of ferulic acid derivatives containing an β-amino alcohol

BackgroundPlant diseases caused by viruses and bacteria cause huge economic losses due to the lack of effective control agents. New potential pesticides can be discovered through biomimetic synthesis and structural modification of natural products. A series of ferulic acid derivatives containing an β-amino alcohol were designed and synthesized, and their biological activities were evaluated.ResultBioassays results showed that the EC50 values of compound D24 against Xanthomonas oryzae pv. oryzae (Xoo) was 14.5 μg/mL, which was better than that of bismerthiazol (BT, EC50 = 16.2 μg/mL) and thiodiazole copper (TC, EC50 = 44.5 μg/mL). The in vivo curative and protective activities of compound D24 against Xoo were 50.5% and 50.1%, respectively. The inactivation activities of compounds D2, D3 and D4 against tobacco mosaic virus (TMV) at 500 μg/mL were 89.1, 93.7 and 89.5%, respectively, superior to ningnanmycin (93.2%) and ribavirin (73.5%). In particular, the EC50 value of compound D3 was 38.1 μg/mL, and its molecular docking results showed that compound D3 had a strong affinity for TMV-CP with a binding energy of − 7.54 kcal/mol, which was superior to that of ningnanmycin (− 6.88 kcal /mol).ConclusionsThe preliminary mechanism research results indicated that compound D3 may disrupt the three-dimensional structure of the TMV coat protein, making TMV particles unable to self-assemble, which may provide potential lead compounds for the discovery of novel plant antiviral agents.Graphical

Synthesis of β-Amino Alcohols from Value-Added Plant-Polyphenols Using ACC as a Green Reaction Medium and Mechanistic Study from DFT Analysis

A simple, new, and cost-efficient alternative route has been designed for the synthesis of unique β-amino alcohols under metal-free condition from new type of 1,2- disubstituted styrene epoxides obtained from substituted p-hydroxycinnamic acids via greener approach. It was followed by density functional theory (DFT) based computational study to investigate the mechanistic path for generating acetylated amino alcohols i.e. the main key step for the formation of β-amino alcohols.

Eugenol β-Amino/β-Alkoxy Alcohols with Selective Anticancer Activity.

Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol β-amino alcohol and β-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three β-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.

Tunable synthesis of furfurylamines or β-amino alcohols via Ru-catalyzed N–H functionalization using biomass-derived polyols

We report the highly efficient conversion of readily available biomass-derived polyols with amines to valuable furfurylamines or β-amino alcohols compounds using ruthenium catalysis. The reaction outcome is readily tuned by the simple addition of 4 ​Å molecular sieves (furfurylamines vs.β-amino alcohols) with high chemo-selectivity. The proposed reaction mechanism involves ruthenium-catalyzed hydrogen borrowing for the reduction of the imine intermediate and C–C bond cleavage of polyols via a retro-aldol process. A series of arylamines was successfully transformed into the desired products with moderate to good yields.

Efficient photocatalytic epoxidation of styrene over a quantum-sized SnO2 on carbon nitride as a heterostructured catalyst

Styrene oxide is a pivotal organic intermediate in pharmaceuticals and fine chemicals synthesis. However, the current synthesis process relies on the use of peroxy acid or chlorohydrin, which is incompatible with establishing a more sustainable chemical industry. Here, we reported the synthesis of a quantum-sized SnO2 on 2D graphitic carbon nitride (CN) as a heterostructured catalyst, which displays efficient photocatalytic styrene epoxidation at room temperature using O2 as a mild oxidant, achieving styrene conversion of 98.1% and styrene oxide yield of 71.8%. Photoelectrochemical analysis demonstrates efficient electron transferring exists from CN to SnO2, which enhances charge carriers’ separation and transfer processes. Furthermore, we couple the photocatalytic styrene epoxidation with epoxide ring-opening amination, achieving the synthesis of value-added β-amino alcohol in a cascade reaction fashion. This work may shed light on the heterostructured catalyst design for photocatalytic selective synthesis of valuable chemicals in a sustainable manner.

Ruthenium-catalyzed acceptorless dehydrogenative coupling of amino alcohols and ynones to access 3-acylpyrroles.

Herein, a new strategy for the direct synthesis of functionalized pyrroles from β-amino alcohols and ynones via ruthenium-catalyzed acceptorless dehydrogenative coupling has been demonstrated. This developed methodology proceeds in an atom- and step-economic fashion together with the merits of broad substrate scope, operational simplicity, and water and hydrogen gas as the sole by-products, which provides an alternative and sustainable way to access functionalized pyrroles. Further, this method was applied to the rapid synthesis of the COX-1/COX-2 inhibitor and boron dipyrromethene derivative successfully.

Facile synthesis of eight-membered cyclic(ester-amide)s and their organocatalytic ring-opening polymerizations

Facile modular synthesis of eight-membered cyclic(ester-amide)s based on phthalic anhydride and β-amino alcohols and organocatalitic ROP of the monomers to afford degradable semi-aromatic poly(ester-amides)s with tunable thermal properties.

Synergistic effect of GO/SrFe12O19 as magnetic hybrid nanocatalyst for regioselective ring-opening of epoxides with amines under eco-friendly conditions.

Herein, a highly efficient magnetically separable hybrid GO/SrFe12O19 nanocomposite was synthesized via dispersing M-type strontium hexaferrite (SrFe12O19) on graphene oxide (GO) sheets. First, SrFe12O19 nanoparticles (NPs) and GO sheets were prepared via chemical coprecipitation and chemical oxidation of graphite powder, respectively. Chemically reduced GO (rGO) and rGO/SrFe12O19 were also prepared for comparison purposes. Thereafter, the prepared nanostructured materials were explored by XRD, FTIR, FESEM-EDX, BET, and Zetasizer analyses. All the characterizations confirm the nanoscale and the high stability structures of the prepared materials. The prepared hybrid magnetic nanocomposite GO/SrFe12O19 exhibited a high surface area value resulting in a high catalytic activity and selectivity for the epoxide ring-opening with amines in neat water. The use of hybrid GO/SrFe12O19 compared with pure SrFe12O19 and GO sheets is of great interest for using environmentally benign heterogeneous nanocatalysts, for the synthesis of β-amino alcohols, with excellent recyclability under eco-friendly conditions. Moreover, a mechanistic study was performed through density functional theory (DFT) calculations and Parr functions to explain the observed reactivity and selectivity of SrFe-GO catalyst in the epoxide ring-opening reactions.

Tetraarylphosphonium salt-catalyzed formal [3+2] cycloaddition between epoxides and trichloroacetonitrile for the synthesis of β-amino alcohol derivatives.

Efficient regioselective synthesis of β-amino alcohol derivatives, including enantioenriched ones, by a tetraarylphosphonium salt-catalyzed coupling reaction of epoxides with trichloroacetonitrile is described. Formal [3+2] cycloaddition, followed by hydrolysis, proceeded smoothly to afford N-protected β-amino alcohols in good yields.

α-Hydroxylation of α,α-Disubstituted N-tert-Butanesulfinyl Ketimines with Molecular Oxygen: Stereoselective Synthesis of α-Tertiary Hydroxyimines.

α-Tertiary hydroxyimines were stereoselectively synthesized from enantioenriched N-tert-butanesulfinyl ketimines using potassium tert-butoxide, molecular oxygen, and trimethyl phosphite. The stereoselective hydroxylation of acyclic ketimines bearing two sterically similar α-substituents was achieved by controlling the geometry of the metalloenamine intermediates and the facial selectivity of hydroxylation. The synthetic utility of the resulting α-tertiary hydroxyimines was demonstrated through the successful diastereoselective synthesis of highly substituted β-amino alcohols.

Phosphorus-Based Organocatalysis for the Dehydrative Cyclization of N-(2-Hydroxyethyl)amides into 2-Oxazolines

A metal-free, biomimetic catalytic protocol for the cyclization of N-(2-hydroxyethyl)amides to the corresponding 2-oxazolines (4,5-dihydrooxazoles), promoted by the 1,3,5,2,4,6-triazatriphosphorine (TAP)-derived organocatalyst tris(o-phenylenedioxy)cyclotriphosphazene (TAP-1) has been developed. This approach requires less precatalyst compared to the reported relevant systems, with respect to the phosphorus atom (the maximum turnover number (TON) ∼ 30), and exhibits a broader substrate scope and higher functional-group tolerance, providing the functionalized 2-oxazolines with retention of the configuration at the C(4) stereogenic center of the 2-oxazolines. Widely accessible β-amino alcohols can be used in this approach, and the cyclization of N-(2-hydroxyethyl)amides provides the desired 2-oxazolines in up to 99% yield. The mechanism of the reaction was studied by monitoring the reaction using spectral and analytical methods, whereby an 18O-labeling experiment furnished valuable insights. The initial step involves a stoichiometric reaction between the substrate and TAP-1, which leads to the in situ generation of the catalyst, a catechol cyclic phosphate, as well as to a pyrocatechol phosphate and two possible active intermediates. The dehydrative cyclization was also successfully conducted on the gram scale.

Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights.

A series of β-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against Sf9 insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY. In addition, the most promising molecules were able to increase the activity of serine proteases (caspases) pivotal to apoptosis and were more toxic to insect cells than human cells. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these molecules likely target acetylcholinesterase and/or the insect odorant-binding proteins and are able to form stable complexes with these proteins. Encapsulation assays in liposomes of DMPG and DPPC/DMPG (1:1) were performed for the most active compound, and high encapsulation efficiencies were obtained. A thermosensitive formulation was achieved with the compound release being more efficient at higher temperatures.

Diastereoselective Three-Component 3,4-Amino Oxygenation of 1,3-Dienes Catalyzed by a Cationic Heptamethylindenyl Rhodium(III) Complex.

The direct oxyamination of olefins is a compelling tool to rapidly access β-amino alcohols-a privileged motif ubiquitous in natural products, pharmaceuticals and agrochemicals. Although a variety of expedient methods are established for simple alkenes, selective amino oxygenation of 1,3-dienes is less explored. Within this context, methods for the oxyamination of 1,3-dienes that are selective for the internal position remain unprecedented. We herein report a modular three-component approach to perform an internal and highly diastereoselective amino oxygenation of 1,3-dienes catalyzed by a cationic heptamethylindenyl (Ind*) Rh(III) complex.