Carbonyl Function Research Articles

Catalytic, Interrupted Carbonyl-Olefin Metathesis for the Formation of Functionalized Cyclopentadienes

Cyclopentadienes are scaffolds in organometallic chemistry, synthetic organic chemistry, and catalysis. We herein describe a regioselective Lewis-acid-catalyzed method for the synthesis of highly functionalized cyclopentadienes incorporating electronically and sterically diverse subunits. Our experimental and theoretical investigations support a mechanism that is related to catalytic carbonyl-olefin metathesis reactions wherein Lewis-acid-catalyzed cycloadditions between carbonyl and alkene functionalities afford reactive oxetane intermediates. However, in lieu of a [2+2]-cycloreversion, stepwise oxetane fragmentation to intermediate carbocations results in the formation of functionalized cyclopentadienes via interrupted carbonyl-olefin metathesis. This work provides insights into the design of catalytic carbonyl-olefin metathesis reactions of aliphatic ketone substrates as stepwise oxetane fragmentation was previously only reported as a competing reaction pathway for aryl ketones.

Towards Arginase Inhibition: Hybrid SAR Protocol for Property Mapping of Chlorinated N-arylcinnamamides.

A series of seventeen 4-chlorocinnamanilides and seventeen 3,4-dichlorocinnamanilides were characterized for their antiplasmodial activity. In vitro screening on a chloroquine-sensitive strain of Plasmodium falciparum 3D7/MRA-102 highlighted that 23 compounds possessed IC50 < 30 µM. Typically, 3,4-dichlorocinnamanilides showed a broader range of activity compared to 4-chlorocinnamanilides. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-en-amide with IC50 = 1.6 µM was the most effective agent, while the other eight most active derivatives showed IC50 in the range from 1.8 to 4.6 µM. A good correlation between the experimental logk and the estimated clogP was recorded for the whole ensemble of the lipophilicity generators. Moreover, the SAR-mediated similarity assessment of the novel (di)chlorinated N-arylcinnamamides was conducted using the collaborative (hybrid) ligand-based and structure-related protocols. In consequence, an 'averaged' selection-driven interaction pattern was produced based in namely 'pseudo-consensus' 3D pharmacophore mapping. The molecular docking approach was engaged for the most potent antiplasmodial agents in order to gain an insight into the arginase-inhibitor binding mode. The docking study revealed that (di)chlorinated aromatic (C-phenyl) rings are oriented towards the binuclear manganese cluster in the energetically favorable poses of the chloroquine and the most potent arginase inhibitors. Additionally, the water-mediated hydrogen bonds were formed via carbonyl function present in the new N-arylcinnamamides and the fluorine substituent (alone or in trifluoromethyl group) of N-phenyl ring seems to play a key role in forming the halogen bonds.

Superbase‐Catalyzed Steric‐Hindrance‐Induced Dimerization of Alkynones to Highly Functionalized Furans

AbstractThe cascade dimerization of alkynones bearing sterically hindered secondary alkyl groups at the carbonyl function has unexpectedly furnished highly functionalized furans. The reaction efficiently occurs in the presence of potassium tert‐butoxide/dimethylsulfoxide superbase catalytic system at room temperature. Alkynones having additional C−H active site at the carbon‐carbon triple bond have followed another dimerization pathway to afford 3‐alkenylpyran‐4‐ones. The discovery of these reactions expands the traditional knowledge about the reactivity of alkynones in strong basic medium.

Co-hydrothermal carbonization of fruit peel with sugars or furfural impacts structural evolution of hydrochar

Both fruit peel and food waste are wet carbonaceous feedstock and they may be processed together via a process such as hydrothermal carbonization. During the co-HTC, the sugars/furfural derived from starch-rich food waste might interact with the fruit peel or its derivatives, influencing the nature of hydrochar and its further activation. This was investigated herein via co-HTC of grapefruit peel with glucose, xylose, or furfural at 180 ºC and the subsequent activation of the resulting hydrochars by K2C2O4 at 750 ºC. The results showed that the sugars and furfural reacted with GP and/or the derivatives, enhancing the hydrochar yields. The presence of furfural rendered the hydrochar from the co-HTC more “densified”, aromatic, and resistant to cracking/gasification during activation, producing the activated carbon of higher yield but with main micropores. The aliphatic glucose and xylose reacted with GP or the derivatives via cross-polymerization through consumption of carbonyl functionality, increasing aromaticity of hydrochar as well but also retaining abundant aliphatic structures, especially glucose. The abundant aliphatic structures in the hydrochar obtained from the co-HTC of GP and glucose facilitated the pore generations in the activation. The specific surface area increased from 753.6 m2g−1 of the control sample to 919.1 m2g−1, which was also accompanied with an increase in mesopore percentage from 48 % to 63 %. The dominance of mesopores facilitated the mass transfer and achieved efficiently the methyl blue adsorption and the capacitance performance over the AC obtained with the co-presence of glucose.

Regio- and chemoselective hydroamination of unactivated alkenes with anthranils via NiH-catalysis.

A NiH-catalyzed polarity-reversed hydroamination of β,γ-, γ,δ- and δ,ε-unsaturated alkenes with electrophilic anthranils was developed. This reaction proceeds in a highly regio- and chemoselective manner to afford γ, δ and ε-arylamines bearing a carbonyl or alcohol functionality with 100% atom efficiency. Preliminary mechanistic studies indicate that the chemoselectivity is controlled by the base and the alcohol product is derived from the base-catalyzed hydrosilylation of the CO bond.

Exploration of bis(pentafluorophenyl)borinic acid as an electronically saturated, bench-top stable Lewis acid catalyst

Bis(pentafluorophenyl)borinic acid was investigated as a bench-stable Lewis acid catalyst for the hydrosilyation of carbonyl functionalities. The reactivity was benchmarked to other effective frustrated Lewis pair catalysts.

Synthesis and characterization of trifluoromethylcarboxonium salts.

The low-temperature protonation of trifluoroacetic acid with the superacids HF/SbF5 and HF/AsF5 resulted in the syntheses of the first examples of trifluoromethylcarboxonium salts. The less acidic trifluoromethylacetamide was also protonated in the same fashion, resulting in exclusive protonation of the carbonyl function. Their [SbF6]- and [AsF6]- salts were characterized by crystal structures, vibrational and multinuclear NMR spectra, and by electronic structure calculations. These salts are thermally unstable, colorless solids, stabilized by very strong hydrogen bonding. The proton NMR resonances of the [CF3C(OH)2]+[SbF6]- and [CF3C(OH)2]+[AsF6]- salts occur at an unprecedented 16.0 and 15.7 ppm, respectively, thus extending the upper limit of the range of observed proton NMR chemical shifts from 14 to 16 ppm.

Differences in the Reactivity of Geminal Si-O-P and Al-O-P Frustrated Lewis Pairs.

The new oxygen-bridged geminal Si/P Frustrated Lewis Pair (FLP) tBu2 P-O-Si(C2 F5 )3 (2) is able to reversibly bind carbon dioxide at ambient temperature. We compared its reactivity towards benzil, but-3-en-2-one, nitriles and phenylacetylene to that of the Al/P FLP tBu2 P-O-AlBis2 (Bis=-CH(SiMe3 )2 ) (1). When reacted with benzil, both, 1 and 2, form the 1,2-addition product, but in the Si/P FLP 2, the second carbonyl function additionally binds to the silicon atom. With but-3-en-2-one 2 forms the 1,2-addition product, while 1 binds in 1,4-position. The reaction with acetonitrile yielded an unexpected etheneimine adduct for both systems, while only 1 reacted with tert-butylnitrile. With benzonitrile and acrylonitrile, 2 showed reversible addition to the C≡N bond and 1 forms a stable adduct with benzonitrile. Solely 1 shows reactivity towards phenylacetylene affording a mixture of the CH deprotonation adduct tBu2 P(H)-O-AlBis2 (CCPh) and the FLP -C≡C 1,2-addition adduct under ring formation. All compounds were characterized by multinuclear NMR spectroscopy, XRD and elemental analysis.

(3-Methylene-2,3-dihydronaphtho[2,3-b][1,4]dioxin-2-yl)methanol

(3-Methylene-2,3-dihydronaphtho[2,3-b][1,4]dioxin-2-yl)methanol was unexpectedly achieved as the main reaction product while applying a standard Johnson–Corey–Chaykovsky procedure to the 2,3-dihydronaphtho[2,3-b][1,4]dioxine-2-carbaldehyde, aiming at obtaining the corresponding epoxide. The structure of the recovered compound was confirmed through NMR and HRMS, the melting point was measured by DSC, and the organic purity was assessed using HPLC. We hypothesized the possible mechanism for the obtainment of this side product, which should involve the opening of the dioxane ring soon after the nucleophilic attack of the ylide to the carbonyl function. The consequent transfer of the negative charge allows the achievement of the phenolate function. The tautomer further rearranges, forming the unstable oxirane, which opening is favored by the acidic phenolic function, thus closing into the more stable six-membered ring compound. We confirmed the hypothesized reaction mechanism by applying the same reaction conditions while starting from the corresponding methyl ketone. This undesired compound, easily and quantitatively obtained by standard Johnson–Corey–Chaykovsky conditions, could pave the way to a new methodology for the obtainment of 2,3-disubstituted 1,4-naphthodioxanes, further derivatizable.

COX-2 and iNOS inhibitory abietane diterpenoids from Pinus yunnanensis exudates

Pinuskesiols A–F (1–6), six new structurally diverse abietane diterpenoids were isolated from Pinus yunnanensis resins. Their structures including absolute configurations were characterized by using spectroscopic and computational methods. All the compounds bear a carbonyl functionality at C-4 with 1 and 2 behaving as a lactone thereof. The isopropyl group is attached to C-13 via O-atom in 3. In addition, the presence of a Δ5(6) double bond and a ketone at C-7 makes 2 a large conjugated system. Biological evaluation revealed that 1, 2, and 4 could concentration-dependently inhibit iNOS and COX-2 expression in lipopolysaccharide-induced RAW 264.7 cells with 2 to be the most active toward COX-2 inhibition.

Copper‐Catalyzed Simultaneous Installation of Boryl and Carbonyl Functionalities to Unsaturated Hydrocarbons

AbstractCu‐catalyzed borylative functionalization of unsaturated hydrocarbons is an effective method for synthesizing various organoboron compounds under mild reaction conditions. In particular, installing carbonyl functionalities such as acyl, formyl, and carboxy groups is interesting because of the essential role of these functionalities in organic synthesis. This review focuses on the installation of boryl and carbonyl functionalities in unsaturated hydrocarbons using Cu catalysts. First, formylation and acylation reactions using formate esters, acyl halides, or acid anhydrides are addressed. Second, the simultaneous incorporation of a boryl group and a carboxy group using carbon dioxide as the electrophile is summarized. Third, the borocyanation of unsaturated hydrocarbons using electrophilic cyanation reagents is described.

Robust Antiviral Activity of Santonica Flower Extract (Artemisia cina) against Avian and Human Influenza A Viruses: In Vitro and Chemoinformatic Studies

The evolution of drug-resistant viral strains following natural acquisition of resistance mutations is a major obstacle to antiviral therapy. Besides the improper prescription of the currently licensed anti-influenza medications, M2-blockers and neuraminidase inhibitors, to control poultry outbreaks/infections potentiates the emergence of drug-resistant influenza variants. Therefore, there is always a necessity to find out new alternatives with potent activity and high safety. Plant extracts and plant-based chemicals represent a historical antiviral resource with remarkable safety in vitro and in vivo to control the emerging and remerging health threats caused by viral infections. Herein, a panel of purified plant extracts and subsequent plant-derived chemicals were evaluated for their anti-avian influenza activity against zoonotic highly pathogenic influenza A/H5N1 virus. Interestingly, santonica flower extract (Artemisia cina) showed the most promising anti-H5N1 activity with a highly safe half-maximal cytotoxic concentration 50 (CC50 > 10 mg/mL) and inhibitory concentration 50 (IC50 of 3.42 μg/mL). To confirm the anti-influenza activity, we assessed the anti-influenza activity of the selected plant extracts against seasonal human influenza A/H1N1 virus and we found that santonica flower extract showed a robust anti-influenza activity that was comparable to the activity against influenza A/H5N1. Furthermore, the mode of action for santonica flower extract with strong inhibitory activity on the abovementioned influenza strains was elucidated, showing a virucidal effect. To go deeper about the activity of the chemometric component of the extract, the major constituent, santonin, was further selected for in vitro screening against influenza A/H5N1 (IC50 = 1.701 μg/mL) and influenza A/H1N1 (IC50 = 2.91 μg/mL). The oxygen of carbonyl functionality in the cyclohexene ring succeeded to form a hydrogen bond with the neuraminidase active site. Despite the fact that santonin revealed similarity to both reference neuraminidase inhibitors in forming hydrogen bonds with essential amino acids, it illustrated shape alignment to oseltamivir more than zanamivir according to Tanimoto algorithms. This study highlights the applicability of santonica flower extract as a promising natural antiviral against low and highly pathogenic influenza A viruses.

Organocatalytic Enantioselective Synthesis of Axially Chiral Molecules: Development of Strategies and Skeletons.

The growing importance of axially chiral architectures in different scientific domains has unveiled shortcomings in terms of efficient synthetic access and skeletal variety. This account describes our strategies in answering these challenges within the organocatalytic context where the emergence of bifunctional catalysts such as chiral phosphoric acids (CPAs) has proven invaluable in controlling the sense of axial chirality. The wide occurrence of bi(hetero)aryl skeletons in privileged structures constitutes a strong motivation to devise more effective arylation methods. Our design revolves around modulating the intrinsic nucleophilicity of aromatic amines and alcohols. The first approach involves the design of an electron-withdrawing activating group which could associate with the catalyst for reactivity enhancement and selectivity control. The resonance of arenes offers the unique mechanistic possibility to select between activating sites. C2-Azo- and nitroso-substituted naphthalenes undergo atroposelective ortho C- or N-arylation with (hetero)aromatic nucleophiles. For monocyclic benzenes, programmable charge localization leads to regioselective activation by catalytic control alone or aided by substrate design. For instance, selective addition to nitroso nitrogen enables successive annulation initiated by the amine to yield axially chiral N-arylbenzimidazoles. In a biomimetic manner, a finely tuned catalyst could direct a para-selective nucleophilic approach in the atroposelective arylation of azobenzenes. The second strategy employs electrophilic arene precursors for arylation which occurs via rearomatization with central-to-axial chirality transfer. This enabled the arylation of (imino)quinones with indoles to access phenylindole atropisomers. By adapting this chemistry with an additional oxidation event to liberate the carbonyl functionalities, aryl-o-naphthoquinone and aryl-p-quinone atropisomers were attained. Along with the development of new arylation strategies, deriving new axially chiral structures has been another consistent theme of our research program. The atroposelective functionalization of alkynes provides broad entry to atropisomeric alkenes. The monofunctionalization of alkynes through the interception of an electrophilic vinylidene-quinone-methide (VQM) intermediate with 2-naphthols yielded the new EBINOL scaffolds. By designing an internal directing group, the atroposelective dihalogenation of alkynes was realized using abundant alkali halides despite their weak nucleophilicities and poor solubilities. The atroposelective N-alkylation of alkenes was pursued to prepare multifunctionalized alkene atropisomers that could be converted into 2-arylpyrroles with chirality transfer. The synthesis of B-aryl-1,2-azaborines containing a C-B chiral axis was accomplished where the CPA catalyst effects the desymmetrization and defines the configuration of the distal C-B bond. Inspired by the axially chiral scaffold of allenes, we leveraged the developed arene activation strategy to achieve para-addition and dearomatization of judiciously designed azobenzenes, which led to structurally novel cyclohexadienylidene-based hydrazones. To complement these structures, axially chiral cyclohexadienyl oxime ethers were also attained through CPA-catalyzed condensation between hydroxylamines and spiro[4.5]trienones.

High clarity polyurethane laminating adhesives based on poly (propylene glycol). Effect of hard segment on microphase morphology, haze and adhesion

Within this publication, the performance of high clarity polyurethane adhesives based on a poly(propylene glycol) soft-phase within a polycarbonate or ethanolamine surface-treated polycarbonate laminate, is described. A series of polyurethanes were prepared, with poly(propylene glycol) used as soft-phase due to the high clarity of this polyol and absence of carbonyl functionality, which allows for hard-phase architecture to be resolved with greater resolution. In total, eight adhesives were synthesised, each contained a different chain-extender formulation to gauge what influence hard-phase architecture had on laminate haze and peel strength. This was investigated using either 4,4-methylene diphenyl diisocyanate or isophorone diisocyanate as hard-phase with trimethylolpropane as the only chain-extender or by including one of the following sterically hindered diols: 2,2-diethyl-1,3-propane diol, 1,3-butane diol or 1,2-proane diol. DSC analysis showed that microphase morphology was strongly influenced by the diisocyanate present, as shown by the degree of phase mixing being greater in methylene diphenyl diisocyanate based formulations when compared with isophorone diisocyanate based. ATR complements this observed difference in microphase morphology, with isophorone diisocyanate based formulations having a greater composition of hydrogen-bonded urethane and urea functionality present within the hard-phase which displays a more phase separated composition. Interestingly, differences in microphase mixing did not have a consistent influence on the peel strength obtained, with only 31% of laminate combinations tested recording a peel strength of <3 N mm −1 after 18 months. Diol chain-extended formulations based on methylene diphenyl diisocyanate accounted for 25% of these lower values and was a consequence of their poorer process-ability during lamination. This resulted in higher haze values being encountered for both polycarbonate and ethanolamine surface-treated polycarbonate laminates which contained methylene diphenyl diisocyanate based formulations when compared to isophorone diisocyanate based formulations, where all values were <1.5%.

Catalytic screening of the cascade reductive amination reaction of furfural and acetonitrile

The reductive amination reaction of furfural with acetonitrile has been explored employing various catalytic systems based on supported Rh, Ru, Pt and Pd nanoparticles. The synthesis of Rh and Ru nanoparticles supported on titania was accomplished following an environmentally friendly two step-protocol, based on the microwave assisted preparation of TiO2 and its subsequent functionalization by an impregnation/chemical reduction method. Commercial Pd/C, Pt/C and Ru/C were additionally evaluated to get insights into the effect of the metal component into the reaction progress and the products selectivity. Interestingly, the metal component resulted to have a drastic influence into the selectivity of the reaction. In particular, catalytic materials based on rhodium supported on TiO2, led to the selective formation of the reductive amination products, namely towards the secondary and tertiary amines, derived from the hydrogenated furfural ring. In turn, ruthenium-based materials drove the reaction progress towards the hydrogenation of the carbonyl functionality and did not favor the hydrogenation of the furan ring, similar to the behavior observed for platinum system. Furthermore, palladium-based catalyst favored the hydrogenation of the aldehyde group and, moreover, led to the hydrogenation of the furan ring. Products characterization was carried out by GC-MS and NMR spectroscopies. Outstanding conversion (>99%) and selectivity (76%) values towards the N-ethyl-N-((tetrahydrofuran-2-yl)methyl)ethanamine were reached for the TiO2-Rh1% catalyst.

Tunable Multi-Phase System for Highly Chemo-Selective Oxidation of Hydroxymethyl-Furfural.

Three different multiphase systems (MP 1-3) comprised of two immiscible liquids, with or without an ionic liquid (IL: methyltrioctyl ammonium chloride), were investigated for the oxidation of 5-hydroxymethyl-furfural (HMF) over 5 % Ru/C as a catalyst and air (8 bar) as an oxidant. These conditions proved versatile for an excellent control of the reaction selectivity to 4 distinct products derived from full or partial oxidation of the carbonyl and alcohol functions of HMF, and each one achieved in 87-96 % isolated yield at complete conversion. MP1 based on water and isooctane, yielded 2,5-furandicarboxylic acid (FDCA, 91 % yield). In MP2, obtained by adding the IL to MP1, the oxidation proceeded towards the formation of 5-formyl-2-furancarboxylic acid (FFCA, 87-89 % yield). MP2 also proved successful in the design of a one pot-two step oxidation/reduction sequence to prepare 5-hydroxymethyl-2-furancarboxylic acid (HMFCA, 85 % yield). In MP3, the use of an acetonitrile/cyclooctane biphase yielded 2,5-diformylfuran (DFF, 96 % yield). All the multiphase systems MP 1-3 allowed a perfect segregation of the catalyst in a single phase (either the hydrocarbon or the IL) distinct from the one containing HMF and its oxidation products. This was crucial not only for the catalyst/product separation but also for the recycle of Ru/C that was possible under all the tested conditions. Accordingly, MP-reaction were run in a semicontinuous mode without removing the catalyst from the reactor nor resorting to conventional separation and activation techniques. Negligible Ru leaching, less than 0.96 ppb, was measured in all cases.

Total Synthesis of (-)-Cylindricine H.

Starting from (R)-phenylglycinol-derived tricyclic lactam 1, the enantioselective synthesis of (-)-cylindricine H is reported. From the stereochemical standpoint, the key steps are the stereoselective generation of the quaternary C10 stereocenter, the stereoselective introduction of the C4 acetoxy and C2 butyl substituents taking advantage of the lactam carbonyl functionality, and the assembly of the pyrrolidine ring with the required functionalized one-carbon chain at C13 by intramolecular opening of an epoxide.

How do zeolite-templated carbons grow?

Major insights into the formation mechanism of zeolite-templated carbons (ZTCs) were achieved via a thorough ex situ kinetic study of the hybrid (carbon/zeolite) and carbon materials. In depth characterization of the chemical, electrical, textural, and morphological properties of the materials allowed us to draw a precise picture of the key steps of the ZTC formation. An in situ time resolved GC study enabled us to achieve complementary insights into the ethylene consumption and hydrogen production during ZTC synthesis. Three stages could be disclosed: nucleation, growth and condensation. During nucleation, individual polyaromatic hydrocarbons (PAHs) develop through the aromatization of ethylene. These PAHs present high spin concentration and react upon zeolite dissolution, leading to unstructured carbon particles of undefined morphology. These carbons feature persistent radicals. During growth, the PAHs evolve to form more complex rylene-type molecules. Typical structural, textural, and morphological features of ZTCs start to emerge during this second stage. The evolution of electrical conductivity of hybrid materials indicates partial condensation of PAHs throughout the zeolite crystals leading to their connection. The carbon materials achieved during the second stage can be described as composites of ZTCs and randomly reacted PAHs. Condensation, which is importantly induced by heat treatment, triggers full connection of the ZTC network. Textural, morphological, structural, and electrical features develop, which result directly from zeolite templating. Final ZTCs feature carbonyl functionalization, which is inherent to the zeolite dissolution step and probably results from radical quenching with water.

Chemical Characterization and Visualization of Progressive Brown Rot Decay of Wood by Near Infrared Imaging and Multivariate Analysis.

Brown rot fungi cause a type of wood decay characterized by carbohydrate degradation and lignin modification. The chemical and physical changes caused by brown rot are usually studied using bulk analytical methods, but these methods fail to consider local variations within the wood material. In this study we applied hyperspectral near infrared imaging to Scots pine sapwood samples exposed to the brown rot fungi Coniophora puteana and Rhodonia placenta to obtain position-resolved chemical information on the fungal degradative process. A stacked-sample decay test was used to create a succession of decay stages within the samples. The results showed that the key chemical changes associated with decay were the degradation of amorphous and crystalline carbohydrates and an increase in aromatic and carbonyl functionality in lignin. The position-resolved spectral data revealed that the fungi initiated degradation in earlywood, and that earlywood remained more extensively degraded than latewood even in advanced decay stages. Apart from differences in mass losses, the two fungi produced similar spectral changes in a similar spatial pattern. The results show that near infrared imaging is a useful tool for analyzing brown rot decayed wood and may be used to advance our understanding of fungal degradative processes.

Palladium‐Catalyzed Oxidation of Glucose in Glycopeptides**

AbstractSelective modification of carbohydrate residues in glycopeptides is highly relevant as a tool in glycobiology. In particular, oxidation allows for subsequent ligation with a label or handle and can be effectuated enzymatically or chemically. Chemical oxidation of carbohydrate residues in glycopeptides is nearly invariably done using periodate cleavage, leading to aldehydes. In this work, we applied palladium‐catalyzed oxidation for the same purpose. The catalyst, [(neocuproine)PdOAc]2OTf2, developed for the site‐selective oxidation of mono‐ and oligosaccharides on preparative scale, proved suitable for the oxidation of glucose residues in a series of glucopeptides. Careful optimization of the reaction conditions is necessary to get acceptable conversions without excessive over‐oxidation of amino acid side‐chains, in particular threonine. The resulting carbonyl function can be used for an oxime‐ligation to biotin. A protocol for the analysis of the products using mass spectrometry is also reported.