Formation Of Alkyl Research Articles

Quantum-chemical study of alkyl- and alkenyladamantanes formation by ionic alkylation with olefins

In B3LYP-D3(BJ)/6-311++G** approximation thermodynamic parameters of formation reactions (total energy at 0 К, enthalpy and the Gibbs free energy at temperature 298.15 К and pressure 101325 Pa) are assessed for the products of ionic alkylation of adamantane and lower alkyladamantanes with ethylene and propylene. Aluminium chloride was used as acid catalyst model. Quantum-chemical calculations demonstrate the influence of methyl groups in adamantanes and olefin molecular weight on energetics of formation of relevant alkyl- and alkenyladamantanes.

Photocatalyzed Direct C(sp3)-H Alkenylation of Unactivated Alkanes via Tandem C-C Activation of Cyclopropenes.

A highly adaptable method has been developed for the alkenylation of a broad spectrum of inert alkanes, employing milder reaction conditions. Tetrabutylammonium decatungstate (TBADT) serves as a photocatalyst for hydrogen atom transfer (HAT), instigating the formation of transient alkyl radicals through C(sp3)-H functionalization. These radicals exhibit regioselective addition to cyclopropenes, followed by the subsequent activation of C-C bonds, forming the corresponding vinylated derivatives. This methodology accommodates diverse unreactive C(sp3)-H bond motifs and multisubstituted cyclopropenes, enabling the efficient synthesis of highly functionalized olefins with high diastereoselectivity.

The role of water in APCI-MS online monitoring of gaseous n-alkanes

In atmospheric pressure chemical ionization mass spectrometry (APCI-MS), [M−3H+H2O]+ ions can deliver analyte-specific signals that enable direct analysis of volatile n-alkane mixtures. The underlying ionization mechanisms have been the subject of open debate, and in particular the role of water is insufficiently clarified to allow for reliable process analytics when the humidity level changes over time. This can be a problem, particularly in online monitoring, where analyte accumulation in the ion source can also occur. Here, we investigated the role of water during APCI-MS of volatile n-alkanes by changing the carrier gas for sample injection from a dry to a wetted state as well as by using 18O-labeled water. This allowed for a distinction between gaseous and surface-adsorbed water molecules. While adsorbed water seems to be responsible for the desired [M−3H+H2O]+ signals through surface reactions with the analyte molecules, gaseous water was found to promote the formation of CnH2n+1O+ of different (and analyte-independent) hydrocarbons, revealing a reaction with hydrocarbon species which accumulated in the ion source during continuous operation. At the same time, gaseous water competed with analyte molecules for ionization and thus suppressed the formation of alkyl (CnH2n+1+) and alkenyl (CnH2n−1+) ions. The results reveal a memory effect due to hydrocarbon adsorption, which may cause severe interpretation difficulties when the ionization chamber undergoes sudden humidity changes. The use of [M−3H+H2O]+ for n-alkane analysis in alkane/water mixtures can be facilitated by constantly maintaining high humidity and hence stabilizing the ionization conditions.Graphical abstract

In situ copper photocatalysts triggering halide atom transfer of unactivated alkyl halides for general C(sp3)-N couplings

Direct reduction of unactivated alkyl halides for C(sp3)-N couplings under mild conditions presents a significant challenge in organic synthesis due to their low reduction potential. Herein, we introduce an in situ formed pyridyl-carbene-ligated copper (I) catalyst that is capable of abstracting halide atom and generating alkyl radicals for general C(sp3)-N couplings under visible light. Control experiments confirmed that the mono-pyridyl-carbene-ligated copper complex is the active species responsible for catalysis. Mechanistic investigations using transient absorption spectroscopy across multiple decades of timescales revealed ultrafast intersystem crossing (260 ps) of the photoexcited copper (I) complexes into their long-lived triplet excited states (>2 μs). The non-Stern-Volmer quenching dynamics of the triplets by unactivated alkyl halides suggests an association between copper (I) complexes and alkyl halides, thereby facilitating the abstraction of halide atoms via inner-sphere single electron transfer (SET), rather than outer-sphere SET, for the formation of alkyl radicals for subsequent cross couplings.

Dual Nickel- and Photoredox-Catalyzed Asymmetric Reductive Cross-Couplings: Just a Change of the Reduction System?

ConspectusIn recent years, nickel-catalyzed asymmetric coupling reactions have emerged as efficient methods for constructing chiral C(sp3) carbon centers. Numerous novel approaches have been reported to rapidly construct chiral carbon-carbon bonds through nickel-catalyzed asymmetric couplings between electrophiles and nucleophiles or asymmetric reductive cross-couplings of two different electrophiles. Building upon these advances, our group has been devoted to interrogating dual nickel- and photoredox-catalyzed asymmetric reductive cross-coupling reactions.In our endeavors over the past few years, we have successfully developed several dual Ni-/photoredox-catalyzed asymmetric reductive cross-coupling reactions involving organohalides. While some probably think that this system is just a change of the reduction system from traditional metal reductants to a photocatalysis system, a question that we also pondered at the beginning of our studies, both the achievable reaction types and mechanisms suggest a different conclusion: that this dual catalysis system has its own advantages in the chiral carbon-carbon bond formation. Even in certain asymmetric reactions where the photocatalysis regime functions only as a reducing system, the robust reducing capability of photocatalysts can effectively accelerate the regeneration of low-valent nickel species, thus expanding the selectable scope of chiral ligands. More importantly, in many transformations, besides reducing nickel catalysts, the photocatalysis system can also undertake the responsibility of alkyl radical formation, thereby establishing two coordinated, yet independent catalytic cycles. This catalytic mode has been proven to play a crucial role in achieving diverse asymmetric coupling reactions with great challenges.In this Account, we elucidate our understanding of this system based on our experience and findings. In the Introduction, we provide an overview of the main distinctions between this system and traditional Ni-catalyzed asymmetric reductive cross-couplings with metal reductants and the potential opportunities arising from these differences. Subsequently, we outline various chiral carbon-carbon bond-forming types obtained by this dual Ni/photoredox catalysis system and their mechanisms. In terms of chiral C(sp3)-C(sp2) bond formation, extensive discussion focuses on the asymmetric arylations of α-chloroboronates, α-trifluoromethyl alkyl bromides, α-bromophosphonates, and so on. In the realm of chiral C(sp3)-C(sp) bond formation, asymmetric alkynylations of α-bromophosphonates and α-trifluoromethyl alkyl bromides have been presented herein. Regarding C(sp3)-C(sp3) bond formation, we take the asymmetric alkylation of α-chloroboronates as a compelling example to illustrate the great efficiency of this dual catalysis system. This summary would enable a better grasp of the advantages of this dual catalysis system and clarify how the photocatalysis regime facilitates enantioselective transformations. We anticipate that this Account will offer valuable insights and contribute to the development of new methodologies in this field.

Selective Electrochemical Modification and Degradation of Polymers

AbstractWe demonstrate that electrochemical‐induced decarboxylation enables reliable post‐polymerization modification and degradation of polymers. Polymers containing N‐(acryloxy)phthalimides were subjected to electrochemical decarboxylation under mild conditions, which led to the formation of transient alkyl radicals. By installing these redox‐active units, we systematically modified the pendent groups and chain ends of polyacrylates. This approach enabled the production of poly(ethylene‐co‐methyl acrylate) and poly(propylene‐co‐methyl acrylate) copolymers, which are difficult to synthesize by direct polymerization. Spectroscopic and chromatographic techniques reveal these transformations are near‐quantitative on several polymer systems. Electrochemical decarboxylation also enables the degradation of all‐methacrylate poly(N‐(methacryloxy)phthalimide‐co‐methyl methacrylate) copolymers with a degradation efficiency of >95 %. Chain cleavage is achieved through the decarboxylation of the N‐hydroxyphthalimide ester and subsequent β‐scission of the backbone radical. Electrochemistry is thus shown to be a powerful tool in selective polymer transformations and controlled macromolecular degradation.

Selective Electrochemical Modification and Degradation of Polymers.

We demonstrate that electrochemical-induced decarboxylation enables reliable post-polymerization modification and degradation of polymers. Polymers containing N-(acryloxy)phthalimides were subjected to electrochemical decarboxylation under mild conditions, which led to the formation of transient alkyl radicals. By installing these redox-active units, we systematically modified the pendent groups and chain ends of polyacrylates. This approach enabled the production of poly(ethylene-co-methyl acrylate) and poly(propylene-co-methyl acrylate) copolymers, which are difficult to synthesize by direct polymerization. Spectroscopic and chromatographic techniques reveal these transformations are near-quantitative on several polymer systems. Electrochemical decarboxylation also enables the degradation of all-methacrylate poly(N-(methacryloxy)phthalimide-co-methyl methacrylate) copolymers with a degradation efficiency of >95 %. Chain cleavage is achieved through the decarboxylation of the N-hydroxyphthalimide ester and subsequent β-scission of the backbone radical. Electrochemistry is thus shown to be a powerful tool in selective polymer transformations and controlled macromolecular degradation.

Quantum-Chemical Study of Formation of Alkyl- and Alkenyladamantanes by Ionic Alkylation with Olefins

Quantum-Chemical Study of Formation of Alkyl- and Alkenyladamantanes by Ionic Alkylation with Olefins

Formation of alkoxymethyl hydroperoxides and alkyl formates from simplest Criegee intermediate (CH2OO) + ROH (R=CH3, CH3CH2, and (CH3)2CH) reaction systems

Formation of alkoxymethyl hydroperoxides and alkyl formates from simplest Criegee intermediate (CH2OO) + ROH (R=CH3, CH3CH2, and (CH3)2CH) reaction systems

Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction

Chemically modified nucleosi(ti)des and functional oligonucleotides (ONs, including therapeutic oligonucleotides, aptamer, nuclease, etc.) have been identified playing an essential role in the areas of medicinal chemistry, chemical biology, biotechnology, and nanotechnology. Introduction of functional groups into the nucleobases of ONs mostly relies on the laborious de novo chemical synthesis. Due to the importance of nucleosides modification and aforementioned limitations of functionalizing ONs, herein, we describe a highly efficient site-selective alkylation at the C8-position of guanines in guanosine (together with its analogues), GMP, GDP, and GTP, as well as late-stage functionalization of dinucleotides and single-strand ONs (including ssDNA and RNA) through photo-mediated Minisci reaction. Addition of catechol to assist the formation of alkyl radicals via in situ generated boronic acid catechol ester derivatives (BACED) markedly enhances the yields especially for the reaction of less stable primary alkyl radicals, and is the key to success for the post-synthetic alkylation of ONs. This method features excellent chemoselectivity, no necessity for pre-protection, wide range of substrate scope, various free radical precursors, and little strand lesion. Downstream applications in disease treatment and diagnosis, or as biochemical probes to study biological processes after linking with suitable fluorescent compounds are expected.

Hollow AMn2O4-δ (A = Co, Zn, Ni) nanotube for direct photo-oxidation of methane to C1 and C2 alcohols at atmospheric pressure and room temperature

Methane (CH4) conversion is brought into research hotspot in the field of environment, and direct photo-oxidation of methane into C1 and C2 alcohols under moderate conditions remains a huge challenge. Herein, we report a series of hollow AMn2O4-δ (A = Co, Zn, Ni) spinel nanotubes (HNTs) for the direct photo-oxidation of methane (DPOM) reaction. The results of catalytic performance demonstrated that the CH4 conversion and the yields of high value-added liquid products arrange in order of ZnMn2O4-δ HNTs > CoMn2O4-δ HNTs > NiMn2O4-δ HNTs. The ZnMn2O4-δ HNTs exhibited a superior CH4 conversion of 53.9 %, a liquid product yield of 241.7 μmol g−1h−1 (CH3OH 40.1 μmol g−1h−1, CH3CH2OH 200.9 μmol g−1h−1) and a selectivity of 100 % under light irradiation at atmospheric pressure and room temperature conditions. Xray photoelectron spectroscopy (XPS) and low-temperature electron paramagnetic resonance (EPR) analysis showed that the substitution of Zn ion at the A-site of manganate spinel significantly improved surface chemisorbed oxygen (Oα) and oxygen vacancy activity, which were beneficial to the formation of •CH3. Multi-technology photocatalytic activity characterizations results showed that ZnMn2O4-δ HNTs possessed a narrower band gap and greatly favored the separation of photogenerated carriers. Moreover, the DPOM reaction mechanism involving the formation and dehydrogenation of alkyl and alkoxy intermediates was proposed over AMn2O4-δ (A = Zn, Co, Ni) HNTs, which was investigated through temperature-programmed desorption of CH4 (CH4-TPD), in situ EPR, in situ Fourier transform infrared spectroscopy (FT-IR) and density functional theoretical (DFT) calculations. It emphasized that CH3OH was formed via the combination of •CH3 and •OH. And it was more inclined to generate CH3CH2OH through the intermediates *CH2CH3/*CH3O. This study could broaden the avenue toward the application of manganese-based spinel in the direct photo-oxidation of methane into alcohols and offer a disparate perspective on the role of the substitution of metal ion at the A-site in enhancing the photocatalytic performance.

Preparation and characterization of aspirin–fucoidan complex and its admirable antitumor activity on human non-small cell lung cancer cells

The purpose of this work is to prepare a novel acetylated derivative of Undaria pinnatifida fucoidan (UPFUC) with admirable antitumor activity. Fucoidan was first acetylated by acetylsalicylic acid (aspirin, ASA) to form the ASA-UPFUC complex. The antitumor efficacy results stated that ASA-UPFUC inhibited the proliferation of human non-small cell lung cancer A549 cells in a dose-dependent manner, with an IC50 value of 49.09 μg/mL, 50.20 % lower than that of UPFUC. Importantly, the acetylation process had no adverse effects on the backbone structure of UPFUC. Simultaneously, ASA-UPFUC demonstrated a larger charge density than UPFUC, leading to enhanced solubility, improved surface charge effects, and a greater potential for exerting biological activity. Consequently, ASA-UPFUC increased the formation of alkyl and hydrogen bonds with tumor necrosis factor related apoptosis-inducing ligand receptors DR4 and DR5, thereby effectively stimulating the generation of cellular reactive oxygen species, diminishing mitochondrial membrane potential, suppressing nuclear factor κB (NFκB) p65 phosphorylation, enhancing the contents of Bax and cleaved caspase 3, and reducing the level of Bcl-2. The collective effects ultimately triggered the mitochondrial apoptotic pathway, leading to apoptosis in A549 cells. The findings support the potential utilization of ASA-UPFUC as a novel dietary additive for human lung cancer chemoprevention.

Particulate-bound alkyl nitrate pollution and formation mechanisms in Beijing, China

Abstract. Fine particulate matter (PM2.5) samples were collected between November 2020 and October 2021 at the Minzu University of China in Beijing, and the n-alkyl nitrate concentrations in the PM2.5 samples were determined to investigate n-alkyl nitrate pollution and formation mechanisms. C9–C16 n-alkyl nitrate standards were synthesized, and the n-alkyl nitrate concentrations in PM2.5 were determined by gas chromatography triple quadrupole mass spectrometry. Temporal trends in and correlations between particulate-bound n-alkyl nitrate, ozone, PM2.5, and nitrogen dioxide concentrations were investigated to assess the relationships between particulate-bound n-alkyl nitrate concentrations and gas-phase homogeneous reactions in the photochemical process and speculate the particulate-bound n-alkyl nitrates' formation mechanisms. The n-alkyl nitrate concentrations in the PM2.5 samples were 9.67–2730 pg m−3, and the mean was 578 pg m−3. The n-alkyl nitrate homologue group concentrations increased as the carbon chain length increased; i.e., long-chain n-alkyl nitrates contributed more than short-chain n-alkyl nitrates to the total n-alkyl nitrate concentrations in PM2.5. The n-alkyl nitrate concentrations clearly varied seasonally and diurnally, the concentrations decreasing in the order winter > spring > autumn > summer and the mean concentrations being higher at night than in the day. The particulate-bound n-alkyl nitrate and ozone concentrations significantly negatively correlated despite gas-phase alkyl nitrate and ozone concentrations previously being found to positively correlate. This indicated that long-chain alkyl nitrates may not be produced during gas-phase homogeneous reactions. The particulate-bound n-alkyl nitrate concentrations followed the same trends as and significantly positively correlated with the PM2.5 and nitrogen dioxide concentrations. Nitrogen dioxide is an important contributor of nitrates in particulate matter. This indicated that particulate-bound n-alkyl nitrates may form through non-homogeneous reactions between alkanes and nitrates on particulate matter surfaces. As secondary pollutants, particulate-bound alkyl nitrates are important components of PM2.5 during haze events and strongly affect haze pollution and atmospheric visibility.

Photoexcitation of (diarylmethylene)amino benziodoxolones for alkylamination of styrene derivatives with carboxylic acids.

The alkylamination of alkenes using pristine carboxylic acids was achieved by the photoexcitation of (diarylmethylene)amino benziodoxolones (DABXs), which serve as both an oxidant and an aminating reagent (an iminyl radical precursor). The developed method is a simple photochemical reaction without the need for external photosensitizers and shows a broad substrate scope for aliphatic carboxylic acids leading to the formation of primary, secondary, and tertiary alkyl radicals, thus enabling the facile synthesis of various structurally complex amines. Mechanistic investigations including transient absorption spectroscopy measurements using a laser flash photolysis (LFP) method disclosed the unique photochemical reactivity of DABXs, which undergoes homolysis of their I-N bonds to give an iminyl radical and ortho-iodobenzoyloxy radical, the latter of which participates in the single-electron oxidation of carboxylates.

Correction to “Organophotoredox-Catalyzed Formation of Alkyl–Aryl and −Alkyl C–S/Se Bonds from Coupling of Redox-Active Esters with Thio/Selenosulfonates”

Correction to “Organophotoredox-Catalyzed Formation of Alkyl–Aryl and −Alkyl C–S/Se Bonds from Coupling of Redox-Active Esters with Thio/Selenosulfonates”

Copper-Catalyzed Enantioconvergent Radical C(sp3)-N Cross-Coupling to Access Chiral α-Amino-β-lactams.

A copper-catalyzed enantioconvergent radical C(sp3)-N cross-coupling of racemic tertiary α-bromo-β-lactams with aromatic amines is developed under mild thermal reaction conditions. The use of a sterically demanded oxazoline-derived sulfonamide N,N,N-ligand is crucial for the reaction initiation and effective enantio-discrimination of the azetidinone-derived cyclic alkyl radicals. The strategy provides an attractive approach to access chiral α-amino-β-lactams, an important structural motif in many biologically active molecules. Preliminary mechanistic studies support the formation of azetidinone-derived alkyl radicals from the L*Cu(I)-amido complex and α-bromo-β-lactams.

Theoretical determination of the standard enthalpies of formation of alkyl radicals using the concept of a complete set of homodesmotic reactions

The complete sets of homodesmotic reactions (HDR) for 107 acyclic alkyl free radicals С4-С9 of normal and branched structure were constructed using the graph-theoretic representation and analysis of a tested compound. The absolute enthalpies of the studied compounds and HDR reference structures were calculated using the M062X/cc-pVTZ level of theory. Based on these data, the thermal effects of HDRs were calculated and then applied to determine the standard enthalpies of formation of the studied radicals using the known enthalpies of formation of reference structures. The dissociation energies of BDE C–H and C–CH3 bonds were also calculated. The effect of radical structure on the BDE value is discussed, and a new effect of stabilization of the radical center in the skewed conformation of free radical is established; this effect has not been previously described in the scientific literature.

A Photoinduced Palladium-Catalyzed Cascade Reaction for the Synthesis of Chiral Piperidines with Chiral Amino Acid Derivatives and 1,3-Dienes

AbstractA photoinduced palladium-catalyzed cascade reaction involving remote C(sp3)–H functionalization and intramolecular Tsuji–Trost annulation is developed. The reaction is proposed to proceed through a sequence involving the amidyl radical generation, 1,5-HAT-mediated alkyl radical formation, and subsequent difunctionalization of 1,3-dienes. Without the use of exogeneous photosensitizers and external oxidants, the reaction provided an efficient approach to multi-substituted chiral piperidines in high yields, employing readily available chiral amino acid derivatives and 1,3-dienes as the substrates. In most cases, the syn/anti ratio of the product could be further improved by treatment with catalytic amount of iron salt.

2,2'-Biquinoline-Based Recyclable Electroauxiliaries for the Generation of Alkyl Radicals via C-C Bond Cleavage.

Alkyl radical precursors are essential for a wide variety of photocatalytic and 3d-metal-catalyzed C-C bond forming reactions. Neutral organic heterocycles as electroauxiliaries such as 4-alkyl Hantzsch esters have become reliable tools for alkyl radical formation. Here we show that 2,2'-biquinoline-derived alkyl-substituted dihydroquinolines act as competent radical precursors with the ability to form primary, secondary and tertiary alkyl radicals. Hydroalkylation of benzalmalononitriles and N-Boc protected diazenes has been achieved through copper catalysis under mild conditions of 50 °C with good to very good yields of up to 85 %. Furthermore, the dihydroquinolines' reactivity towards a denitrative alkylation of nitroolefins such as β-nitrostyrene was discovered. Most importantly, the released biquinoline can be recycled, which greatly improves the overall atom-economy of these alkyl radical precursors in comparison to previous N-heterocyclic electroauxiliaries.

On the Role of N-Heterocyclic Carbene Salts in Alkyl Radical Generation from Alkyl Alcohols: A Computational Study.

Formation of carbon-carbon bonds through cross-coupling reactions using readily available substrates, like alcohols, is crucial for modern organic chemistry. Recently, direct alkyl alcohol functionalization has been achieved by the use of N-Heterocyclic Carbene (NHC) salts via in situ formation of an alcohol-NHC adduct and its activation by a photoredox catalyst to generate carbon-centered alkyl radicals. Experimentally, only electron deficient NHC activators work but the reasons of this behavior remain underexplored. Herein, a DFT computational study of the mechanism of alcohol activation using up to seven NHC salts is performed to shed light into the influence of their electronic properties in the alkyl radical formation. This study demonstrates that four reaction steps are involved in the transformation and characterizes how the electronic properties of the NHC salt affect each step. A fine balance of the NHC electron-richness is proved to be determinant for this transformation.