Amine Functionality Research Articles

Boron-Thioketonates: A New Class of S,O-Chelated Boranes as Acceptors in Optoelectronic Devices.

Development of new n-type semiconductors with tunable band gap and dielectric constant has significant implication in dissociating bound charge carrier relevant for demonstrating high performance optoelectronic devices. Boron-β-thioketonates (MTDKB), analogues to boron-β-diketonates containing a sulfur atom in the framework of β-diketones were synthesized. Bulk transport measurement exhibited an outstanding bulk electron mobility of ≈0.003 cm2 V-1 s-1 , which is among the best values reported till date in these class of semiconducting materials and correspondingly a single junction photo responsivity of upto 6 mA W-1 was obtained. This new family of O,S-chelated boron compounds exhibited luminescence in the far red/near-infrared region. The remarkable red shift of 89 nm (fluorescence) observed for 4 a in comparison with analogues boron-β-diketonate signifies the importance of sulfur in these molecules. MTDKBs with amine functionality have also been investigated as an ON/OFF fluorescent sensor.

Porous titania beads for remediation of arsenic contamination from acid mine drainage

Hierarchically porous titania beads with and without amine functionalisation have been developed and tested as adsorbents for removal of highly toxic As(V) from environments affected by acid mine drainage (AMD). The unique acid stability of the titania framework enables these adsorbents to function in highly acidified environments and their granular form facilitates practical deployment under continuous flow conditions. Herein, both non-functionalised and amine-functionalised titania beads have been demonstrated to selectively remove As(V) from simulated and real AMD solutions at pH 2.6. Novel selectivity for As(V) over Na(I), Mg(II), Al(III), Si(VI), Ca(II), Co(II), Cu(II), Zn(II), Nd(III) and Ho(III) was achieved, with competing element concentrations similar to or up to an order of magnitude greater than that of As(V). Although Fe(III) and some Fe(II) were also adsorbed by the titania beads, Fe adsorption did not inhibit As(V) adsorption, indicating different adsorption mechanisms for these two elements. The As(V) adsorption capacity of the titania beads decreased from ∼20 mg/g from pure As(V) solution to ∼10 mg/g from real AMD solution, demonstrating the importance of adsorbent testing under applied conditions. Amine functionalisation increased the kinetics of adsorption, but the non-functionalised titania beads showed greater selectivity for As(V) over Fe(II) and Fe(III) and hence were considered preferable for As remediation applications. Nevertheless, the functionalisation ability of the porous titania beads makes them a promising, flexible technology for remediation of a wide range of AMD affected environments.

Amphiphilic Dendrimer Doping Enhanced pH-Sensitivity of Liposomal Vesicle for Effective Co-delivery toward Synergistic Ferroptosis-Apoptosis Therapy of Hepatocellular Carcinoma.

Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxides, has emerged as an attractive strategy to reverse drug resistance. Of particular interest is the ferroptosis-apoptosis combination therapy for cancer treatment. Herein, a nanoplatform is reported for effective co-delivery of the anticancer drug sorafenib (S) and the ferroptosis inducer hemin (H), toward synergistic ferroptosis-apoptosis therapy of advanced hepatocellular carcinoma (HCC) as a proof-of-concept study. Liposome is an excellent delivery system; however, it is not sufficiently responsive to the acidic tumor microenvironment (TME) for tumor-targeted drug delivery. The pH-sensitive vesicles are therefore developed (SH-AD-L) by incorporating amphiphilic dendrimers (AD) into liposomes for controlled and pH-stimulated release of sorafeniband hemin in the acidic TME, thanks to the protonation of numerous amine functionalities in AD. Importantly, SH-AD-L not only blocked glutathione synthesis to disrupt the antioxidant system, but also increased intracellular Fe2+ and ·OH concentrations to amplify oxidative stress, both of which contribute to enhanced ferroptosis. Remarkably, high levels of ·OH also augmented sorafenib-mediated apoptosis in tumor cells. This study demonstrates the efficacy of ferroptosis-apoptosis combination therapy, as well as the promise of the AD-doped TME-responsive vesicles for drug delivery in combination therapy to treat advanced HCC.

Lithium, Tin(II), and Zinc Amino-Boryloxy Complexes: Synthesis and Characterization.

Analogous to the ubiquitous alkoxide ligand, metal boroxide and boryloxy complexes are an underexplored class of hard anionic O- ligand. A new series of amine-stabilized Li, Sn(II), and Zn boryloxy complexes, comprising electron-rich tetrahedral boron centers have been synthesized and characterized. All complexes have been characterized by one-dimensional (1D), two-dimensional (2D), and DOSY NMR, which are consistent with the solid-state structures unambiguously determined via single-crystal X-ray diffraction. Electron-rich μ2- (Sn and Zn) and μ3- (Li) boryloxy binding modes are observed. Compounds 6-9 are the first complexes of this class, with the chelating bis- and tris-phenol ligands providing a scaffold that can be easily functionalized and provides access to the boronic acid pro-ligand, hence allowing facile direct synthesis of the resulting compounds. Computational quantum chemical studies suggest a significant enhancement of the π-donor ability of the amine-stabilized boryloxy ligand because of electron donation from the amine functionality into the p-orbital of the boron atom.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) adsorbed on microplastics in drinking water: Implications for female exposure, reproductive health risk and its mitigation strategies through in silico methods

In this paper, molecular dynamics (MD) simulations were used to analyze the effects of different additive combinations in microplastics (MPs) on the female reproductive toxicity of perfluoroalkyl and polyfluoroalkyl substances (PFAS). It was found that 59.38% of plastic additive combinations had synergistic toxicity effects. And the plastic additive combination scheme with 31.10% decrease of joint toxic action was selected. By simulating the PFAS adsorption by MPs in drinking water through MD, it was found that hydrophobic PFAS was more easily adsorbed by MPs, and the van der Waals interaction energy may have an influential role in MPs adsorbing PFAS. The degree of interference with PFAS adsorption by MPs is greater when the MP is supplemented with a more hydrophobic additive. During AC adsorbing PFAS and MPs, it was found that some of the PFAS was adsorbed by MPs, and improving the adsorption of MPs by AC could also improve the removal rate of PFAS from drinking water. The effect of hydrophobic natural organic matter (NOM) on AC adsorbing PFAS and MPs was more significant, and the higher the molecular weight, the greater the effect on the adsorption performance of the AC. Within a certain range, ACs show an increasing tendency to adsorb PFAS and MPs with decreasing pore size and increasing amine functionalization. Machine learning method was used to get the influence rule of molecular parameters on improving PFAS function and reducing female reproductive toxicity. This study aims to mitigate the toxic hazards to female reproductive from current exposure to PFAS through drinking water, and to provide theoretical guidance for designing PFAS alternatives with low female reproductive toxicity.

Pressure-Induced Hysteretic and Abrupt Spin Transition in Amine Functionalized Isoquinoline-Based Two-Dimensional FeII Hofmann Frameworks

Two two-dimensional (2D) Hofmann-type coordination frameworks are synthesized by employing the square planar tetracyanometallate building blocks and an amine-functionalized isoquinoline ligand with the general formula of [Fe(L)2{M(CN)4}] (L = 5-amino isoquinoline) (M = Pt (1Pt) and Pd (1Pd)) to explore the spin-state switching behavior. The inclusion of the amine functional group in the isoquinoline ligand plays a major role in exhibiting a complete spin crossover (SCO) behavior under ambient atmospheric pressure. The effective host–host supramolecular interaction such as strong π···π stacking and N–H···C interactions between interlayer 2D sheets of {FeII[Pt (CN)4]}n is responsible for the abrupt hysteretic spin transition behavior. Interestingly, the applied external pressure enhances the stabilization of the low spin states revealing a one-step abrupt and hysteretic spin transition near room temperature.

Distal meta-alkenylation of formal amines enabled by catalytic use of hydrogen-bonding anionic ligands

•Distal C–H activation mediated by non-covalent interactions •Catalytic amount of anionic ligand induces H-bonding interaction with amides •H bonding enables Pd-catalyzed distal meta-activation •Amines with variable linker lengths are susceptible to this protocol Regioselective and site-selective functionalization of distal C–H bonds has remained a significant challenge over the last decades. Although covalently attached directing groups have been designed to help solve this puzzle, their profound impact on step economy significantly hinders the protocol’s applicability. Weak non-covalent interactions have been developed to overcome this, but they have mainly been explored with Ir catalysis. Herein, we aim to execute a Pd-catalyzed meta-selective C–H functionalization of simple amines by harnessing weak non-covalent interactions between an anionic ligand and neutral substrate. A catalytic amount of organic salt acts as a suitable ligand for efficient meta-selective C–H olefination. Experimental and computational studies suggest that site selectivity is governed by the key H-bonding interaction between an anionic donating ligand and neutral motifs. The protocol can be further extended to amines with variable linker lengths, outlining the versatility and applicability of our methodology, while utilizing only a catalytic amount of directing ligand for the transformation. Regioselective and site-selective functionalization of distal C–H bonds has remained a significant challenge over the last decades. Although covalently attached directing groups have been designed to help solve this puzzle, their profound impact on step economy significantly hinders the protocol’s applicability. Weak non-covalent interactions have been developed to overcome this, but they have mainly been explored with Ir catalysis. Herein, we aim to execute a Pd-catalyzed meta-selective C–H functionalization of simple amines by harnessing weak non-covalent interactions between an anionic ligand and neutral substrate. A catalytic amount of organic salt acts as a suitable ligand for efficient meta-selective C–H olefination. Experimental and computational studies suggest that site selectivity is governed by the key H-bonding interaction between an anionic donating ligand and neutral motifs. The protocol can be further extended to amines with variable linker lengths, outlining the versatility and applicability of our methodology, while utilizing only a catalytic amount of directing ligand for the transformation. Charge-controlled Pd catalysis enables the meta-C–H activation and olefination of arenesMondal et al.ChemJanuary 24, 2023In Briefvan Gemmeren and co-workers report a method that enables the meta-selective olefination of arenes on the basis of a charge-controlled Pd-catalyzed C–H activation. The method relies on charge-charge and charge-dipole interactions to achieve unconventional regioselectivities. Mechanistic investigations support this novel means of controlling regioselectivity in Pd-catalyzed C–H activation. A broad scope of functionalized benzyl ammonium products can be accessed, and these are shown to be valuable linchpins for further functionalization toward densely functionalized arenes with challenging substitution patterns. Full-Text PDF Open Access

Catalytic and Aerobic Oxidative C−H Annulation Reaction of Saturated Cyclic Amines for Synthesis of Dipyrroloquinolines

AbstractWith the aim of providing an efficient platform for the one‐step construction of nitrogen‐containing polycyclic frameworks, we report a heterogeneous platinum‐catalyzed oxidative α,β‐C(sp3)−H dual functionalization of saturated cyclic amines. This method involves a tandem oxidative dehydrogenation/hetero Diels‐Alder reaction under aerobic mild conditions, providing tetracyclic octahydro‐dipyrroloquinoline frameworks in good yields. The reaction was applied to the synthesis of natural products incargranine B aglycone and seneciobipyrrolidine in one step. This study provides efficient and rapid access to nitrogen‐containing fused tetracyclic compounds in a highly atom‐economical fashion.magnified image

Primary Amine Functionalized Carbon Dots for Dead and Alive Bacterial Imaging.

Small molecular dyes are commonly used for bacterial imaging, but they still meet a bottleneck of biological toxicity and fluorescence photobleaching. Carbon dots have shown high potential for bio-imaging due to their low cost and negligible toxicity and anti-photobleaching. However, there is still large space to enhance the quantum yield of the carbon quantum dots and to clarify their mechanisms of bacterial imaging. Using carbon dots for dyeing alive bacteria is difficult because of the thick density and complicated structure of bacterial cell walls. In this work, both dead or alive bacterial cell imaging can be achieved using the primary amine functionalized carbon dots based on their small size, excellent quantum yield and primary amine functional groups. Four types of carbon quantum dots were prepared and estimated for the bacterial imaging. It was found that the spermine as one of precursors can obviously enhance the quantum yield of carbon dots, which showed a high quantum yield of 66.46% and high fluorescence bleaching-resistance (70% can be maintained upon 3-h-irradiation). Furthermore, a mild modifying method was employed to bound ethylenediamine on the surface of the spermine-carbon dots, which is favorable for staining not only the dead bacterial cells but also the alive ones. Investigations of physical structure and chemical groups indicated the existence of primary amine groups on the surface of spermine-carbon quantum dots (which own a much higher quantum yield) which can stain alive bacterial cells visibly. The imaging mechanism was studied in detail, which provides a preliminary reference for exploring efficient and environment-friendly carbon dots for bacterial imaging.

Indication of Pd-C or Cu-C Intermediate in Respective Bimetallic Nanoclusters Pd/Au-PVP or Cu/Au-PVP Catalyzed Oxidations of endo-4-Oxatricyclo[5.2.1.02,6]-8-decene and Tetrahydro-γ-carbolines.

Catalytic oxidations of tricyclic endo-norbornene-fused tetrahydrofuran with bimetallic nanoclusters Cu/Au-PVP and H2O2 or t-BuOOH as an oxidant provided C-H bond oxidation adjacent to the ether function and 4-oxa-tricyclo[5.2.1.0]-8,9-exo-epoxydecane (4), however, oxidation with Pd/Au-PVP took place at the C=C function giving epoxide 4 and oxidative three-bond forming dimeric product, dodecahydro-1,4:6,9-dimethanodibenzofurano[2,3-b:7,8-b']bisoxolane (5). Formation of the latter suggests the involvement of a reactive Pd-C intermediate. Similarly, oxidative C-C bond forming reactions were found in cycloaddition reactions of N2-Boc-1,2,3,4-tetrahydro-γ-carbolines and 2,3-dihydroxybenzoic acid with 2 - 5 mol% Cu/Au-PVP and H2O2 at 25 °C, providing two-bond-forming [4+2] cycloadducts. Under similar reaction conditions, Pd/Au-PVP did not produce the cycloadduct, indicating a need of complexation between Cu with the carboxylic acid group of 2,3-dihydroxybenzoic acid and allylic amine function of γ-carbolines in the cyclization reaction. The reported intermolecular coupling reactions using Pd/Au-PVP or Cu/Au-PVP nanocluster catalysts under oxidative conditions at 25 °C are unprecedented.

Biotransformation of the Novel Myeloperoxidase Inhibitor AZD4831 in Preclinical Species and Humans.

We report herein an in-depth analysis of the metabolism of the novel myeloperoxidase inhibitor AZD4831 ((R)-1-(2-(1-aminoethyl)-4-chlorobenzyl)-2-thioxo-2,3-dihydro-1H-pyrrolo[3,2-d]pyrimidin-4(5H)-one) in animals and human. Quantitative and qualitative metabolite profiling were performed on samples collected from mass balance studies in rats and humans. Exposure of circulating human metabolites with comparable levels in animal species used in safety assessment were also included. Structural characterization of 20 metabolites was performed by liquid chromatography high-resolution mass spectrometry, and quantification was performed by either 14C analysis using solid phase scintillation counting or accelerator mass spectrometry and, where available, authentication with synthesized metabolite standards. A complete mass balance study in rats is presented, while data from dogs and human are limited to metabolite profiling and characterization. The metabolism of AZD4831 is mainly comprised of reactions at the primary amine nitrogen and the thiourea sulfur, resulting in several conjugated metabolites with or without desulfurization. A carbamoyl glucuronide metabolite of AZD4831 (M7) was the most abundant plasma metabolite in both human healthy volunteers and heart failure patients after single and repeated dose administration of AZD4831, accounting for 75%-80% of the total drug-related exposure. Exposures to M7 and other human circulating metabolites were covered in rats and/or dogs, the two models most frequently used in the toxicology studies, and were also highly abundant in the mouse, the second model other than rat used in carcinogenicity studies. The carbamoyl glucuronide M7 was the main metabolite in rat bile, while a desulfurized and cyclized metabolite (M5) was abundant in rat plasma and excreta. SIGNIFICANCE STATEMENT: The biotransformation of AZD4831, a novel myeloperoxidase inhibitor inhibiting xanthine derivative bearing thiourea and primary aliphatic amine functions, is described. Twenty characterized metabolites demonstrate the involvement of carbamoylation with glucuronidation, desulfurization, and cyclization as main biotransformation reactions. The carbamoyl glucuronide was the main metabolite in human plasma, likely governed by a significant species difference in plasma protein binding for this metabolite, but this and other human plasma metabolites were covered in animals used in the toxicity studies.

Amine Functionalization Within Hierarchically‐Porous Zeotype Framework for Plasmonic Catalysis over PdAu Nanoparticles

AbstractPlasmonic catalysis has revealed improved product yield and selectivity in various chemical transformation reactions over the past decade. In this report, the effect of tertiary amine (‐NR3) functionalization on the surface of hierarchically‐porous zeotype (HP‐AlPO‐5) materials to enhance the plasmon‐mediated catalysis, utilizing a combination of the plasmonic antenna (Au) and catalytic reactor (Pd) nanoparticles (NPs) was investigated. The catalysts have been characterized using enhanced techniques such as HAADF‐STEM, FT‐EXAFS, and probe‐based FT‐IR to reveal the proximity and interaction between bimetallic NPs, and thermal stability of amines in the presence of Au or PdAu NPs. Interestingly, a four‐fold enhancement in the Suzuki‐Miyaura coupling reaction product yield was obtained over PdAu/HP‐AlPO‐5‐NR3 when compared with the analogous plasmonic catalyst with no amine functionalization under visible light irradiation. A range of amines were functionalized and their influence in the nucleation, uniform growth and stabilization of catalytic active site (Pd) and formation of electron‐rich species under visible light irradiation has also been investigated. The presence of tertiary amine in the nanostructured catalyst enhanced the turnover number (TON) significantly under light irradiation conditions in comparison to dark conditions. This study provides an enriched understanding of plasmon‐driven chemistry, where the maximized reaction rate enhancement requires the existence of active metal species and the formation of electron‐enriched species under light irradiation conditions.

Investigations of Nanoparticle Suspensions of Prussian Blue and Its Copper Analogue: Amine Functionalization and Electrochemical Studies

Prussian blue (PB) and its analogues are promising materials for electrochemical energy storage, yet their use in flow-type devices is limited by their lack of redox responsiveness as colloidal suspensions. We have investigated the redox chemistry amine functionalization of PB along with its Cu analogue (CuPBA). No redox response of colloidal PB was observed and suspensions of CuPBA formed films on electrode surfaces with and without applied potentials; the films were redox-active but the material that remained suspended in solution did not participate in redox chemistry. Propylamine (pa), ethylenediamine (en), or tetramethylethylenediamine (TMEDA) were added in an attempt to maintain well dispersed suspensions through nanoparticle surface functionalization. Propylamine modifications resulted in a loss of the CuPBA network and subsequent precipitation of insoluble materials. Coordination of ethylenediamine prompted the formation of Cu and Fe monomers ([Cu(en)2]m+/[Fe(CN)6]n-]) that remained soluble in aqueous electrolytes. In the absence of supporting electrolytes, these monomers formed a one-dimensional (1D) polymeric structure (Cu2Fe-1D). TMEDA modification preserved the CuPBA extended structure with only modest precipitate formation over 30 min. The redox responsiveness of these suspensions depended on conditions; in 1 M KCl, no redox chemistry was observed for the CuPBA. In pH 4 potassium hydrogen phthalate buffer, a signal was observed that was attributed to the Fe centers of CuPBA. Under these conditions, the material precipitated in ∼15 min and the signal was lost. Although the Fe centers in these networks are redox-active, additional work is needed to realize longer-term redox activity and stability. Ligand modifications can alter the properties of these networks but within a given ligand class, e.g., amines, the effects can vary greatly from the deconstruction of the framework to preventing film formation.

Metal-Free Amine-Anchored Triazine-Based Covalent Organic Polymers for Selective CO2 Adsorption and Conversion to Cyclic Carbonates Under Mild Conditions

Attaining both large uptake and high conversion of CO2 under mild reaction conditions within a metal-free covalent organic polymer (COP) is an attractive and challenging strategy for CO2 utilization because CO2 is an abundant and renewable C1 source and a main greenhouse gas. In this study, novel amine-anchored covalent triazine aromatic polymers (CTP-1-NH2 and CTP-2-NH2) were synthesized from 2-amino-4,6-dichloro-1,3,5-triazine, biphenyl, and 1,3,5-triphenylbenzene via facile Friedel–Crafts arylation for CO2 adsorption and conversion reaction. At 273 K and 1 bar, CTP-1-NH2 and CTP-2-NH2 exhibited CO2 uptakes of 187.4 and 224.41 mg/g and CO2/N2 selectivity of 69.45 and 61.38, respectively, outperforming many previously reported COP materials. Moreover, metal-free CTP-1-NH2 with tetrabutylammonium bromide (n-Bu4NBr) exhibited high epoxide conversion and product selectivity under mild (40 °C and 1 bar) and solvent-free conditions within 36 h of reaction time, which were very much comparable to the performances of many metal-coordinated COP catalysts. The spent catalyst was also highly reusable with no active species leaching. A plausible mechanism for CO2 cycloaddition over the CTP-1-NH2 catalyst is proposed. Incorporating amine functionalities into a nitrogen-rich structure could be a promising strategy for developing materials with simultaneous CO2 capture and conversion.

Synthesis of Dihydropyridine Spirocycles by Semi-Pinacol-Driven Dearomatization of Pyridines

The identification of the beneficial pharmacokinetic properties of aza-spirocycles has led to the routine incorporation of these highly rigid and three-dimensional structures in pharmaceuticals. Herein, we report an operationally simple synthesis of spirocyclic dihydropyridines via an electrophile-induced dearomative semi-pinacol rearrangement of 4-(1'-hydroxycyclobutyl)pyridines. The various points for diversification of the spirocyclization precursors, as well as the synthetic utility of the amine and ketone functionalities in the products, provide the potential to rapidly assemble medicinally relevant spirocycles.

Transition‐Metal‐Free Methods for the Remote C−H Bond Functionalization of Cyclic Amines

AbstractC−H bond functionalization is one of the most efficient strategies for the rapid synthesis of cyclic amines containing substituents in the ring, which are core structures of many bioactive molecules. However, it is much more challenging to perform this strategy on remote C−H bonds than on α‐C−H bonds of cyclic amines. This review provides a comprehensive overview on the transition metal‐free methods for the remote C−H bond functionalization of cyclic amines, complementary to methods relying on transition metal catalysis. Selected substrate scope and discussion of reaction mechanism are given when necessary.

Plasma-Functionalised Dressings for Enhanced Wound Healing.

Fundamental knowledge about cell-surface interactions can be applied in the development of wound dressings and scaffolds to encourage wounds to heal. As surfaces produced with acid-functionalised monomers encourage keratinocyte adhesion, proliferation and migration, whilst amine functionalisation enhances fibroblast proliferation and migration in vitro, standard care wound dressings were plasma-coated with either acrylic acid or allylamine and applied to 6 mm excisional wounds on the backs of mice to test their effectiveness in vivo. At day 3, the rate of wound healing was increased in mice treated with dressings that were plasma-coated with allylamine compared to uncoated dressings, with a significantly reduced wound area. However, healing may be impaired following prolonged treatment with allylamine-functionalised dressings, with delayed re-epithelialisation and increased cellularisation of the wound site at later timepoints. Acrylic acid functionalisation, however, offered no early improvement in wound healing, but wounds treated with these dressings displayed increased collagen deposition at day 7 post wounding. These results suggest that plasma polymerisation may allow for the development of new dressings which can enhance wound closure by directing cell behaviour, but that the application of these dressings may require a timed approach to enhance specific phases of the wound healing response.

Iminium and azonium-activated metal and oxidant-free C-H functionalization of aliphatic amines.

A wide variety of synthetic methods have been developed for the synthesis of functionalized aliphatic amines because of their broad utility in both synthetic and medicinal chemistry. The synthesis of functionalized aliphatic amines via direct C-H functionalization of readily available aliphatic amines, the majority of which rely on the use of metallic reagents/catalysts and hazardous oxidants, is advantageous in comparison to the classical multistep approaches. However, the scope to carry out such direct C-H functionalization of aliphatic amines under metal and oxidant-free conditions is being continuously explored. As a result, the examples of C-H functionalization of aliphatic amines employing iminium/azonium ions, which are formed via classical condensation of amines and carbonyl/nitroso compounds, are on the rise. This article summarizes the recent developments in the iminium and azonium-activated metal and oxidant-free C-H functionalization of aliphatic amines with the main focus on the intermolecular reactions of iminium/azonium ions, enamines, and zwitterions with suitable nucleophiles, electrophiles and dipolarophiles.

Hydroarylation of alkynes via dual ortho-C-H functionalization of diaryl amines on a dicopper(I,I) platform.

A pyridine and morpholine-functionalized dicopper(I,I)-NHC complex (1) features both terminal and bridging coordination modes of NHC within the same molecule, and catalyzes dual ortho-C-H functionalization of diaryl amines for the hydroarylation of alkynes. A bimetallic construct in catalyst 1 allows sequential activation of ortho-C-H bonds of two aryl units to furnish a wide variety of 9,10-dihydroacridine derivatives without the explicit use of a directing group.

Fragile intermediate identification and reactivity elucidation in electrochemical oxidative α-C(sp3)-H functionalization of tertiary amines.

The direct α-C(sp3)-H functionalization of widely available tertiary amines holds promise for the rapid construction of complex amine architectures. The activation of C(sp3)-H bonds through electron transfer and proton transfer by oxidants, photoredox catalysis and electrochemical oxidation have received wide attention recently. In these reactions, the direct capture and identification of the key reactive radical intermediates are technically difficult due to their short life-time. Herein, an online electrochemical mass spectrometry (MS) methodology was utilized to probe the short-lived intermediates in the electrochemical oxidative α-C(sp3)-H functionalization of tertiary amines. The resulting electrochemical oxidation intermediates, α-amino radical cation and iminium cation were successfully detected. Further, the α-amino C(sp3) radical added to the double bond of a phenyl trans-styryl sulfone, yielding another C(sp3) radical that leads to the final vinylation. Based on the mass spectrometric elucidation of the reactivity of the α-amino radical, a scale-up electrochemical radical vinylation methodology was established, with which a large variety of allylic amines with broad functional group tolerance were synthesized.