Intermediate Alkyl Research Articles

Highly selective α-aryloxyalkyl C-H functionalisation of aryl alkyl ethers.

We report highly selective photocatalytic functionalisations of alkyl groups in aryl alkyl ethers with a range of electron-poor alkenes using an acridinium catalyst with a phosphate base and irradiation with visible light (456 nm or 390 nm). Experiments indicate that the reaction operates via direct single-electron oxidation of the arene substrate ArOCHRR' to its radical cation by the excited state organic photocatalyst; this is followed by deprotonation of the ArOC-H in the radical cation to yield the radical ArOC˙RR'. This radical then attacks the electrophile to form an intermediate alkyl radical that is reduced to complete the photocatalytic cycle. The oxidation step is selective for activated arenes (ArOR) over their non-activated counterparts and the subsequent deprotonation of the methoxy group affords the α-aryloxyalkyl radical that leads to a wide range of functionalised products in good to excellent yield.

Pretreatment of Plastic Waste: Removal of Colorants from HDPE Using Biosolvents.

Plastics recycling remains a challenge due to the relatively low quality of the recycled material, since most of the developed recycling processes cannot deal with the additives present in the plastic matrix, so the recycled products end up in lower-grade applications. The application of volatile organic solvents for additives removal is the preferred choice. In this study, pretreatment of plastic packaging waste to remove additives using biosolvents was investigated. The plastic waste used was high-density polyethylene (HDPE) with blue and orange colorants (pigment and/or dye). The first step was to identify the type of colorants present in the HDPE, and we found that both plastics presented only one colorant that was actually a pigment. Then, limonene, a renewable solvent, was used to solubilize HDPE. After HDPE dissolution, a wide range of alcohols (mono-, di-, and tri-alcohols) was evaluated as antisolvents in order to selectively precipitate the polymer and maximize its purity. The use of limonene as solvent for plastic dissolution, in combination with poly-alcohols with an intermediate alkyl chain length and a large number of hydroxyl (OH) groups, was found to work best as an antisolvent (1,2,3-propanetriol and 1,2,4-butanetriol), leading to a removal of up to 94% and 100% of the blue and orange pigments, respectively. Finally, three cycles of extraction were carried out, proving the capability of the solvent and antisolvent to be recovered and reused, ensuring the economic viability and sustainability of the process. This pretreatment provides a secondary source of raw materials and revenue for the recycling process, which may lead to an increase in the quality of recycled polymers, contributing to the development of an economical and sustainable recycling process.

Methanol to hydrocarbons conversion: Why dienes and monoenes contribute differently to catalyst deactivation?

Dienes, formed at much lower concentrations than monoenes via alkylation of monoenes with formaldehyde (HCHO), have much higher propensity than monoenes to foment catalyst deactivation in methanol-to-hydrocarbons (MTH) conversion over zeolites via HCHO-mediated deactivation pathways. The mechanistic basis for why monoenes and dienes contribute differently to cause catalyst deactivation during MTH is investigated using independent kinetic studies of HCHO reactions with representative monoenes and dienes, i.e., propylene and 1,3-butadiene, over zeolites. Despite 3,6-dihydro-2H-pyran being the predominant product for both propylene/HCHO and 1,3-butadiene/HCHO reactions, a combination of transient and steady-state rate measurements and stoichiometric experiments reveals distinct persistent intermediates being involved in the addition of HCHO to different surface-bound alkyl species derived from propylene and butadiene. These persistent intermediates desorb only via HCHO- and water-mediated proton transfer steps and as such can be sequestered on the catalyst. A nonlinear mixed-effects kinetic model reveals that the intermediate formed during HCHO-diene reactions has a higher steady-state surface coverage and its desorption via HCHO- and water-mediated routes exhibit > 8× and > 3×, respectively, higher rate constants than those during HCHO-monoene reactions. These results evidence the distinct identity, surface coverage, and reactivities of surface-bound alkyl intermediates as critical factors in the much more pernicious effects of dienes compared to monoenes on catalyst lifetime during MTH.

Hydroesterification and difunctionalization of olefins with N-hydroxyphthalimide esters.

Irradiation of aryl esters of N-hydroxyphthalimides in the presence of unactivated olefins promotes a mild and regioselective hydroesterification. Optimal results are obtained with the aid of fac-Ir(dFppy)3 in CH2Cl2. Terminal and 1,1-disubstituted olefins provide primary esters, and trisubstituted olefins provide secondary esters. The anti-Markovnikov selectivity is consistent with alkyl radical intermediates, which are also indicated by the formation of cyclized products from dienes. Mono-acylated diols are formed from tri- and tetrasubstituted olefins in the presence of water.

Effect of Nickel Active Site Density on the Deactivation of Ni-Beta Zeolite Catalysts during Ethene Dimerization

Isolated Ni(II) sites supported on zeolites and other porous materials transform in situ during alkene dimerization to form active Ni(II)-alkyl centers, and their density influences the kinetic orders and mechanisms of deactivation of Ni-Beta zeolites during ethene dimerization (453 K). Ni-Beta containing high Ni site densities shows deactivation rates that are second-order in Ni, consistent with a dual-site deactivation mechanism involving the formation of unreactive Ni-alkyl-Ni intermediates, as confirmed by DFT calculations. Under the same reaction conditions, by contrast, Ni-Beta containing low Ni site densities shows deactivation rates that are first-order in Ni, consistent with a single-site deactivation mechanism reflecting inhibition by strongly bound intermediates derived from heavier alkene oligomers. On Ni-Beta containing low Ni site densities, cofeeding H2 along with ethene results in a higher number of Ni(II)-alkyl intermediates formed at initial reaction times and a concomitant change to deactivation kinetics that become second-order in Ni. These findings reveal the strong influence of the density of active Ni(II)-alkyl centers in porous supports, which depends both on material properties and reaction conditions that generate active centers in situ, on the kinetics and mechanisms of deactivation during alkene oligomerization.

Construction of Acyclic All-Carbon Quaternary Stereocenter Based on Asymmetric Michael Addition of Chiral Amine.

Acyclic asymmetric quaternary stereocenters, which are composed of four carbon-carbon bonds, were finely constructed by utilizing a face-selective alkylation of enolate intermediates derived from an asymmetric Michael addition reaction of a chiral lithium amide with trisubstituted (E)-α,β-unsaturated esters. The present face-selective alkylation was able to employ diverse alkyl halides as an electrophile to afford various Michael adducts having an all-carbon quaternary stereocenter. With regard to the deprotection of the chiral auxiliary, N-iodosuccinimide used in our previous study did not work in the present cases; however, we found that pyridine iodine monochloride in the presence of H2O was effective to remove the bornyl group and the benzyl group on the amino group to provide the β-amino ester derivative.

Polyethylene Hydrogenolysis at Mild Conditions over Ruthenium on Tungstated Zirconia.

Plastics waste has become a major environmental threat, with polyethylene being one of the most produced and hardest to recycle plastics. Hydrogenolysis is potentially the most viable catalytic technology for recycling. Ruthenium (Ru) is one of the most active hydrogenolysis catalysts but yields too much methane. Here we introduce ruthenium supported on tungstated zirconia (Ru-WZr) for hydrogenolysis of low-density polyethylene (LDPE). We show that the Ru-WZr catalysts suppress methane formation and produce a product distribution in the diesel and wax/lubricant base-oil range unattainable by Ru-Zr and other Ru-supported catalysts. Importantly, the enhanced performance is showcased for real-world, single-use LDPE consumables. Reactivity studies combined with characterization and density functional theory calculations reveal that highly dispersed (WOx)n clusters store H as surface hydroxyls by spillover. We correlate this hydrogen storage mechanism with hydrogenation and desorption of long alkyl intermediates that would otherwise undergo further C–C scission to produce methane.

Chain and cluster models of methylaluminoxane as activators of zirconocene hydride, alkyl and metallacyclopropane intermediates in alkene transformations

The reactions of zirconocene hydride, alkyl, and metallacyclopropane intermediates with chain and cluster models of methylaluminoxane (MAO) have been studied using a quantum chemical approach (DFT). These reactions are considered as possible activation steps of the key intermediates in various olefin transformations. Complexes with MAO differing in the structure and stability were tested for the propene insertion stage for which thermodynamic and activation parameters were determined. Comparative analysis of the results demonstrated a significant role of chain and cage MAO structures in the formation of the sites most active toward the alkene.

Lipid Nature and Alkyl Length Influence Lymph Node Accumulation of Lipid‐Polyethylene Glycol Amphiphiles

AbstractImmunomodulatory drugs are of great relevance in the context of vaccine delivery and cancer immunotherapy. Due to the ubiquitous presence of immune cells throughout the body, gaining control over the biodistribution and activity of such drugs is crucial to limit off‐target inflammatory responses. Here, the authors report on lipid‐PEG (polyethylene glycol) amphiphiles as well‐defined amphiphilic carries for lymph node targeted delivery. Comparing cholesterol and dialkyl lipids with different alkyl chain length, the authors found that both the nature of the lipid, as well as, the alkyl chain length have a dramatic influence on cellular uptake and lymph node translocation. Whereas shorter dioctyl‐PEG amphiphiles show overall poor performance, larger dioctadecyl‐PEG amphiphiles are prone to solubility issues. Didodecyl‐PEG amphiphiles with intermediate alkyl chain length are on par with cholesteryl‐PEG amphiphiles in in vitro and in vivo cellular uptake and lymphoid tissue targeting. Immunization with a cholesteryl‐PEG‐imidazoquinoline (TLR7/8 agonist) amphiphile‐adjuvanted model antigen shows induction of immune responses that are qualitatively different from Montanide‐adjuvanted antigen, characterized by effector CD8+ T cells with immediate cytotoxic potential and robust IgG2 antibody responses. These findings provide a rational base for further adjuvant design based on the type of immunity needed for a specific vaccination or therapeutic setting.

Extremely rapid self-reactions of hydrochlorofluoromethanes and hydrochlorofluoroethanes and implications in destruction of ozone

To assess the ozone depletion potentials of hydrochlorofluoromethanes (HCFMs) and hydrochlorofluoroethanes (HCFEs), atmospheric behaviors of these chlorofluorocarbon alternatives with OH radicals were investigated using quantum chemical and kinetic calculations. The results showed that the H-abstraction reactivity of HCFMs initiated by OH radicals enhances with the increase of the chlorination degree. The intermediate alkyl radicals can generate stable chlorofluorocarbons (CFCs) through self-reactions, which may compete with the reactions of radicals with O2 molecules and increase the risk of ozone layer depletion. The self-reactions of HCFEs result in the increase of carbon chain length, and formed hydrochlorofluorocarbons can further react with OH radicals.

Aryl Radical Activation of C–O Bonds: Copper-Catalyzed Deoxygenative Difluoromethylation of Alcohols

Given their ubiquity in natural products and pharmaceuticals, alcohols represent one of the most attractive starting materials for the construction of C-C bonds. We report herein the first catalytic strategy to harness the reactivity of aryl radicals for the activation of C-O bonds in alcohol-derived xanthate esters, allowing for the discovery of the first catalytic deoxygenative difluoromethylation reaction. Under copper-catalyzed conditions, a wide variety of alkyl xanthate esters, readily synthesized from alcohol feedstocks, were activated by catalytically generated aryl radicals and were converted to the alkyl-difluoromethane products via alkyl radical intermediates. This scalable protocol exhibits a broad substrate scope and functional group tolerance, enabling late-stage modification of complex pharmaceutical agents. A one-pot protocol has been developed that allows for the direct use of free alcohols without purification of the xanthate esters. Mechanistic studies are consistent with the hypothesis of aryl radicals being formed and initiating the cleavage of the C-O bonds of xanthate esters, to generate alkyl radicals as the key intermediates. This aryl radical activation approach represents a new strategy for the activation of alcohols as cross-coupling partners.

A Molecular Analogue of the C−H Activation Intermediate of the Silica‐Supported Ga(III) Single‐Site Propane Dehydrogenation Catalyst: Structure and XANES Signature

AbstractPropane dehydrogenation is an important field of research due to an increasing world‐wide demand of propene while classical production routes through naphtha cracking are in decline. In that context, silica‐supported Ga(III) sites, synthesized from surface organometallic chemistry principles, show high selectivity and stability in the propane dehydrogenation reaction. This performance is in significant contrast to the reported fast deactivation and lower selectivity of most Ga2O3 and CrO3 based materials. The Ga‐catalyzed propane dehydrogenation reaction is proposed to proceed through the formation of Ga alkyl intermediates for which it would be desirable to have detailed structural and spectroscopic information. Here, we prepare a consistent series of Ga(III) molecular complexes with varying numbers of alkyl and siloxide ligands; they are characterized by single crystal X‐Ray diffraction and X‐Ray Absorption Near Edge Structure analysis, which is known to be highly sensitive to the Ga coordination environment. We report in particular the structure and the spectroscopic signatures of [Ga(iPr)(OSi(OtBu)3)2(HOSi(OtBu)3)], a molecular mimic of the key proposed reaction intermediates in the Ga‐catalyzed PDH reaction.

Synthesis of Benzo-Fused Cyclic Ketones via Metal-Free Ring Expansion of Cyclopropanols Enabled by Proton-Coupled Electron Transfer.

The metal-free ring expansion of cyclopropanols containing a pendant styrene moiety was successfully achieved using a proton-coupled electron transfer enabled by an organic photoredox catalyst. Through this, variants of 1-tetralone and 1-benzosuberone bearing a substituent at the benzylic position were selectively obtained through the regioselective ring closure of alkyl radical intermediates depending on the substitution pattern of the alkene moiety.

Olefin oligomerization by main group Ga3+ and Zn2+ single site catalysts on SiO2

In heterogeneous catalysis, olefin oligomerization is typically performed on immobilized transition metal ions, such as Ni2+ and Cr3+. Here we report that silica-supported, single site catalysts containing immobilized, main group Zn2+ and Ga3+ ion sites catalyze ethylene and propylene oligomerization to an equilibrium distribution of linear olefins with rates similar to that of Ni2+. The molecular weight distribution of products formed on Zn2+ is similar to Ni2+, while Ga3+ forms higher molecular weight olefins. In situ spectroscopic and computational studies suggest that oligomerization unexpectedly occurs by the Cossee-Arlman mechanism via metal hydride and metal alkyl intermediates formed during olefin insertion and β-hydride elimination elementary steps. Initiation of the catalytic cycle is proposed to occur by heterolytic C-H dissociation of ethylene, which occurs at about 250 °C where oligomerization is catalytically relevant. This work illuminates new chemistry for main group metal catalysts with potential for development of new oligomerization processes.

Transition-Metal-Free Reductive Cross-Coupling Employing Metabisulfite as a Connector: General Construction of Alkyl–Alkyl Sulfones

Transition-Metal-Free Reductive Cross-Coupling Employing Metabisulfite as a Connector: General Construction of Alkyl–Alkyl Sulfones

Effect of alkyl chain length on the antioxidant activity of alkylresorcinol homologues in bulk oils and oil-in-water emulsions

The antioxidant cut-off theory details the importance of fine-tuning antioxidant hydrophobicity to optimize antioxidant effectiveness for a given food system; however, previous research has utilized synthetic antioxidant homologues which fail to align with the food industry’s demand for natural ingredients. Alkylresorcinols represent a natural homologous series of phenolipid antioxidants. The antioxidant activities of individual alkylresorcinol homologues were investigated in bulk oils and oil-in-water emulsions. In oils, antioxidant activity decreased as alkyl chain length increased and there was no effect on rate of loss. In emulsions, optimum antioxidant activity was observed at intermediate alkyl chain length (C21:0) and longer homologues were lost more rapidly. Radical scavenging capacity decreased as alkyl chain length increased but alkylresorcinols were unable to chelate iron. This suggests that intrinsic properties (e.g. radical scavenging capacity) are responsible for the antioxidant activity of alkylresorcinols in oils while physicochemical phenomena (e.g. partitioning) drive antioxidant activity of alkylresorcinols in emulsions.

Recyclization reactions of 8,10-dibromocamphor with Grignard and organolithium compounds

Grignard reagents and organolithium compounds react with 8,10-dibromocamphor to afford substituted 1-methyl-2-methylenebicyclo[3.2.0]heptanes. Recyclization proceeds via intramolecular enolate alkylation and Grob fragmentation of the reaction intermediates. All compounds have been characterized by 1H, 13C and 19F NMR spectroscopy and their chemical composition proved by HRMS analyses. The relative spatial arrangement of substituents in the molecule of (1-methyl-2-methylenebicyclo[3.2.0]heptan-6-yl)diphenylmethanol was studied by NOESY experiments.

(o-Phenylenediamino)borylstannanes: Efficient Reagents for Borylation of Various Alkyl Radical Precursors.

(o-Phenylenediamino)borylstannanes were newly synthesized to achieve radical boryl substitutions of a variety of alkyl radical precursors. Dehalogenative, deaminative, decharcogenative, and decarboxylative borylations proceeded in the presence of a radical initiator to give the corresponding organic boron compounds. Radical clock experiments and computational studies have provided insights into the mechanism of the homolytic substitution (SH 2) of the borylstannanes with alkyl radical intermediates. DFT calculation disclosed that the phenylenediamino structure lowered the LUMO level including the vacant p-orbital on the boron atom to enhance the reactivity to alkyl radicals in SH 2. Moreover, C(sp3 )-H borylation of THF was accomplished using the triplet state of xanthone.

Selective, Catalytic Oxidations of C–H Bonds in Polyethylenes Produce Functional Materials with Enhanced Adhesion

Summary The synthesis of functional and processable polyethylenes from simple vinyl monomers with controlled molecular weights and architectures has been a grand challenge of polymer chemistry. Post-polymerization modification of the homopolymers of ethylene is attractive for this purpose but has been hampered by the lack of efficient methods for the selective functionalization of C–H bonds in polyolefins. We report the selective, catalytic oxidation of C–H bonds in commodity polyethylenes with varying molecular weights and architectures. Remarkably, the functionalized materials, even at low levels of functionalization, exhibit physical properties that are absent in unmodified polyolefins, such as strong adhesion and the ability to be painted with common waterborne latex paint. Such observations indicate that selectively modified polyethylenes as described here may help to transform existing commodity plastics into more valuable and potentially more sustainable materials.

Electroreductive Carbofunctionalization of Alkenes with Alkyl Bromides via a Radical-Polar Crossover Mechanism.

Electrochemistry grants direct access to reactive intermediates (radicals and ions) in a controlled fashion toward selective organic transformations. This feature has been demonstrated in a variety of alkene functionalization reactions, most of which proceed via an anodic oxidation pathway. In this report, we further expand the scope of electrochemistry to the reductive functionalization of alkenes. In particular, the strategic choice of reagents and reaction conditions enabled a radical-polar crossover pathway wherein two distinct electrophiles can be added across an alkene in a highly chemo- and regioselective fashion. Specifically, we used this strategy in the intermolecular carboformylation, anti-Markovnikov hydroalkylation, and carbocarboxylation of alkenes-reactions with rare precedents in the literature-by means of the electroreductive generation of alkyl radical and carbanion intermediates. These reactions employ readily available starting materials (alkyl halides, alkenes, etc.) and simple, transition-metal-free conditions and display broad substrate scope and good tolerance of functional groups. A uniform protocol can be used to achieve all three transformations by simply altering the reaction medium. This development provides a new avenue for constructing Csp3-Csp3 bonds.