Electron-withdrawing CF3 Research Articles

Fluorescence quenching of deprotonated phenylurea through twisting motion induced by an electron-donating substituent group.

The excited-state proton transfer (ESPT) reaction between anthracen-2-yl-3-phenylurea (PUA) derivatives and tetrabutylammonium acetate (TBAAc) in dimethyl sulfoxide (DMSO) solvent was theoretically investigated using time-dependent density functional theory. The electron-donating methoxy group (OMe) and electron-withdrawing trifluoromethyl group (CF3) were bonded to 2PUA to form OMe-2PUA and CF3-2PUA, respectively. Two hydrogen bonds formed in the 1 : 1 hydrogen-bonded complexes between the 2PUA derivative and acetate ion (AcO-), namely N1-H1⋯O1 and N2-H2⋯O2. Strong charge transfer (CT) due to the electron-donating OMe group led to H1 transfer in the S1 state for the OMe-2PUA:AcO- hydrogen-bonded complex. On the contrary, weak CT due to the electron-withdrawing CF3 group led to H2 transfer in the S1 state for CF3-2PUA. After the ESPT reaction, the binding energies of the hydrogen-bonded complexes strongly decreased in both cases, and this promoted the separation of contact-ion pairs (CIPs*) and formed different types of anionic species. CF3-2PUA- could keep its nearly planar structure in the S1 state and emit "abnormal" fluorescence. On the other hand, the anionic OMe-2PUA- underwent a twisting motion to form a twisted structure in the S1 state with very low energy, and this led to a rapid internal conversion (IC) to quench long-wave fluorescence in the emission spectra.

Improving In Vivo Tumor Accumulation and Efficacy of Platinum Antitumor Agents by Electronic Tuning of the Kinetic Lability.

The impact of kinetic lability or reactivity on in vitro cytotoxicity, stability in plasma, in vivo tumor and tissue accumulation, and antitumor efficacy of functional platinum(II) (Pt) anticancer agents containing a O˄O β-diketonate leaving ligand remain largely unexplored. To investigate this, we synthesized Pt complexes [(NH3 )2 Pt(L1-H)]NO3 and [(DACH)Pt(L1-H)]NO3 (L1=4,4,4-trifluoro-1-ferrocenylbutane-1,3-dione, DACH=1R,2R-cyclohexane-1,2-diamine) containing an electron deficient [L1-H]- O˄O leaving ligand and [(NH3 )2 Pt(L2-H)]NO3 and [(DACH)Pt(L2-H)]NO3 (L2=1-ferrocenylbutane-1,3-dione) containing an electron-rich [L2-H]- O˄O leaving ligand. While all four complexes have comparable lipophilicity, the presence of the electron-withdrawing CF3 group was found to dramatically enhance the reactivity of these complexes toward nucleophilic biomolecules. In vitro cellular assays revealed that the more reactive complexes have higher cellular uptake and higher anticancer potency as compared to their less reactive analogs. But the scenario is opposite in vivo, where the less reactive complex showed improved tissue and tumor accumulation and better anticancer efficacy in mice bearing ovarian xenograft when compared to its more reactive analog. Finally, in addition to demonstrating the profound but contrasting impact of kinetic lability on in vitro and in vivo antitumor potencies, we also described the impact of kinetic lability on the mechanism of action of this class of promising antitumor agents.

Ortho-Fluoro or ortho Effect? Oxidative Addition of Zerovalent Nickel into the C-CN Bond of Substituted Benzonitriles.

A recent study of the oxidative addition of zerovalent Ni to the C-CN bond of F-substituted benzonitriles showed significantly increased stabilization of the C-CN oxidative addition products with o-F groups (-6.6 kcal/mol per o-F) compared to m-F groups (-1.8 kcal/mol per m-F). To answer the question of whether this is an o-F effect or an ortho effect, in this study the effect of CF3 and CH3 groups on the oxidative addition of the [Ni(dmpe)] fragment [dmpe = 1,2-bis(dimethylphosphino)ethane] to the C-CN bond of benzonitriles has been studied. A density functional theory study of the reaction pathway between η2-CN complexes and the C-CN oxidative addition products shows stabilization of the C-CN oxidative addition product with the electron-withdrawing CF3 group and destabilization with the electron-donating CH3 group in both tetrahydrofuran and toluene. There is a slightly larger ortho effect with CF3 (-7.4 kcal/mol) than with F. However, due to steric crowding, two o-CF3 groups did not show considerably more stabilization than one o-CF3 group. There is a linear relationship between ΔG° and the number of meta groups (2.0 kcal/mol stabilization per m-CF3 and 0.8 kcal/mol destabilization per m-CH3). On the basis of natural population analysis, as the C-CN bond becomes more polarized, the stability of the C-CN oxidative addition products with respect to the η2-CN complexes increases.

Inductive Effects on Intramolecular Hydrogen Bond Strength: An Investigation of the Effect of an Electron-Withdrawing CF3 Group Adjacent to an Alcohol Hydrogen Bond Donor.

This combined experimental and theoretical study seeks to determine the role that inductive effects have on hydrogen bonds by an investigation into the change in intramolecular hydrogen bond strength in 2-amino-1-trifluoromethylethanol (2ATFME) relative to that in 2-aminoethanol (2AE). Toward this end, the rotational spectra of the normal, 13C, and 15N isotopologues have been measured using Fourier transform microwave spectroscopy and fit to the rotational, quadrupole coupling, and centrifugal distortion constants of the Watson A-reduction Hamiltonian. Structural parameters used to characterize the strength of the intramolecular hydrogen bond have been determined from the experimental structures of both 2ATFME and 2AE as well as from MP2/6-311++G(d,p) calculations. A comparison of these parameters in 2ATFME with those of 2AE indicates that the electron-withdrawing trifluoromethyl CF3 group strengthens the hydrogen bond. These include a 4% decrease in the distance between the donor and acceptor heavy atoms of the hydrogen bond, a 6% increase toward linearity of the OH···N angle, and a 23% decrease of the COH···N torsional angle toward planarity in 2ATFME relative to 2AE. This trend toward increased intramolecular hydrogen bond strength in 2ATFME is also observed within the ab initio structures.

Visible-Light-Induced [4+1] Cyclization-Aromatization of Acylsilanes and α,β-Unsaturated Ketones

Visible-Light-Induced [4+1] Cyclization-Aromatization of Acylsilanes and α,β-Unsaturated Ketones

Inherently Chiral 6,7-Diphenyldibenzo[ e,g ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

Inherently Chiral 6,7-Diphenyldibenzo[ <i>e,g</i> ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Deep-Red and Near-Infrared Iridium Complexes with Fine-Tuned Emission Colors by Adjusting Trifluoromethyl Substitution on Cyclometalated Ligands Combined with Matched Ancillary Ligands for Highly Efficient Phosphorescent Organic Light-Emitting Diodes.

Six novel Ir(C^N)2(L^X)-type heteroleptic iridium complexes with deep-red and near-infrared region (NIR)-emitting coverage were constructed through the cross matching of various cyclometalating (C^N) and ancillary (LX) ligands. Here, three novel C^N ligands were designed by introducing the electron-withdrawing group CF3 on the ortho (o-), meta (m-), and para (p-) positions of the phenyl ring in the 1-phenylisoquinoline (piq) group, which were combined with two electron-rich LX ligands (dipba and dipg), respectively, leading to subsequent iridium complexes with gradually changing emission colors from deep red (≈660 nm) to NIR (≈700 nm). Moreover, a series of phosphorescent organic light-emitting diodes (PhOLEDs) were fabricated by employing these phosphors as dopant emitters with two doping concentrations, 5% and 10%, respectively. They exhibited efficient electroluminescence (EL) with significantly high EQE values: >15.0% for deep red light0 (λmax = 664 nm) and >4.0% for NIR cases (λmax = 704 nm) at a high luminance level of 100 cd m−2. This work not only provides a promising approach for finely tuning the emission color of red phosphors via the easily accessible molecular design strategy, but also enables the establishment of an effective method for enriching phosphorescent-emitting molecules for practical applications, especially in the deep-red and near-infrared region (NIR).

Inkable CF3-functionalized benzothiazole/benzimidazole-Ir(III) complexes for efficient bilayer-inkjet-printed OLEDs

The inkjet-printed organic light-emitting diodes (OLEDs) are gradually gaining popularity due to their low cost, free vacuum environment, patterning, and large-area display capability, but inkable phosphors are yet less reported. In order to develop inkable phosphorescent luminescent material, the introduction of the strong electron-withdrawing CF3 in the C^N ligand of iridium(III) [Ir(III)] complexes is a wise choice. Herein, a serials of phosphorescent Ir(III) complexes consisting of 2-phenybenzothiazole/1,2-diphenylbenzimidazole with the introduction of CF3 group at ortho (o)/meta (m)/para (p) position of the phenyl ring abbreviated as (obt)2Ir(acac), (mbt)2Ir(acac), (pbt)2Ir(acac), (obm)2Ir(acac), (mbm)2Ir(acac), (pbm)2Ir(acac), respectively, were designed and synthesized. The substituent effect and position effect of CF3 group based on the Ir(III) complexes were investigated in all aspects. The bilayer-inkjet-printed OLEDs with those phosphors were studied and showed promising electroluminescent performances. Among them, the OLEDs with (obt)2Ir(acac)/(obm)2Ir(acac) emitter exhibited the maximum external quantum efficiency of 3.7%/3.3%. In addition, the vacuum-deposited OLEDs with those Ir(III) phosphors as emitters were further investigated and demonstrated outstanding device performance.

Critical Role of CF3 Groups in the Electronic Stabilization of [PdAu24(C≡CC6H3(CF3)2)18]2- as Revealed by Gas-Phase Anion Photoelectron Spectroscopy.

The role of alkynyl ligands with electron-withdrawing nature in the stability of metal clusters was investigated by gas-phase anion photoelectron spectroscopy (PES) on heteroleptic cluster anions [PdAu24(C≡CArF)18-x(C≡CPh)x]2- (ArF = 3,5-(CF3)2C6H3). Gas-phase PES on the cluster anions with specific x (= 0-6) revealed that electron binding energies decreased linearly with x, indicating that the electron-withdrawing CF3 substituents on the alkynyl ligand played a critical role in the electronic stabilization of [PdAu24(C≡CArF)18]2-. Density functional theory calculations reproduced the decrease of electron binding energies and rationally explained the ligand effect by a mechanism similar to the modulation of the work function of gold films by organic monolayers.

Novel Oxidovanadium Complexes with Redox-Active R-Mian and R-Bian Ligands: Synthesis, Structure, Redox and Catalytic Properties.

A new monoiminoacenaphthenone 3,5-(CF3)2C6H3-mian (complex 2) was synthesized and further exploited, along with the already known monoiminoacenaphthenone dpp-mian, to obtain oxidovanadium(IV) complexes [VOCl2(dpp-mian)(CH3CN)] (3) and [VOCl(3,5-(CF3)2C6H3-bian)(H2O)][VOCl3(3,5-(CF3)2C6H3-bian)]·2.85DME (4) from [VOCl2(CH3CN)2(H2O)] (1) or [VCl3(THF)3]. The structure of all compounds was determined using X-ray structural analysis. The vanadium atom in these structures has an octahedral coordination environment. Complex 4 has an unexpected structure. Firstly, it contains 3,5-(CF3)2C6H3-bian instead of 3,5-(CF3)2C6H3-mian. Secondly, it has a binuclear structure, in contrast to 3, in which two oxovanadium parts are linked to each other through V=O···V interaction. This interaction is non-covalent in origin, according to DFT calculations. In structures 2 and 3, non-covalent π-π staking interactions between acenaphthene moieties of the neighboring molecules (distances are 3.36–3.40 Å) with an estimated energy of 3 kcal/mol were also found. The redox properties of the obtained compounds were studied using cyclic voltammetry in solution. In all cases, the reduction processes initiated by the redox-active nature of the mian or bian ligand were identified. The paramagnetic nature of complexes 3 and 4 has been proven by EPR spectroscopy. Complexes 3 and 4 exhibited high catalytic activity in the oxidation of alkanes and alcohols with peroxides. The yields of products of cyclohexane oxidation were 43% (complex 3) and 27% (complex 4). Based on the data regarding the study of regio- and bond-selectivity, it was concluded that hydroxyl radicals play the most crucial role in the reaction. The initial products in the reactions with alkanes are alkyl hydroperoxides, which are easily reduced to their corresponding alcohols by the action of triphenylphosphine (PPh3). According to the DFT calculations, the difference in the catalytic activity of 3 and 4 is most likely associated with a different mechanism for the generation of ●OH radicals. For complex 4 with electron-withdrawing CF3 substituents at the diimine ligand, an alternative mechanism, different from Fenton’s and involving a redox-active ligand, is assumed.

Base-Mediated Claisen Rearrangement of CF3-Containing Bisallyl Ethers.

We have previously clarified that the strongly electron-withdrawing CF3 group nicely affected the base-mediated proton shift of CF3-containing propargylic or allylic alcohols to afford the corresponding α,β-unsaturated or saturated ketones, respectively, which was applied this time to the Claisen rearrangement after O-allylation of the allylic alcohols with a CF3 group, followed by isomerization to the corresponding allyl vinyl ethers via the proton shift, enabling the desired rearrangement in a tandem fashion, or in a stepwise manner, the latter of which was proved to have attained an excellent diastereoselectivity with the aid of a palladium catalyst.

Neutral Cyclometalated Ir(III) Complexes with Pyridylpyrrole Ligand for Photocatalytic Hydrogen Generation from Water.

To explore structure-activity relationships with respect to light-harvesting behavior, a family of neutral iridium complexes [Ir(ppy)2(LR)] 1-4 (where ppy = 2-phenylpyridine, and N̂N = 2-(1H-pyrrol-2-yl)pyridine and its functionalized derivatives) were designed and synthesized. The structural modifications in metal complexes are accomplished through the attributions of electron-donating CH3 in 2, OCH3 in 3, and electron-withdrawing CF3 in 4. The structural analysis displays that the pyridylpyrrole acts as one-negative charged bidentated ligand to chelate the iridium center. The electrochemical and photophysical properties of these complexes were systematically studied. The neutral 1-4 as well as the ionic structurally analogous [Ir(ppy)2(bpy)](PF6) (5) were utilized as PSs in photocatalytic hydrogen generation from water with [Co(bpy)3](PF6)2 as catalyst and triethanolamine (TEOA) as electron sacrificial agent in the presence of salt LiCl. Complex 1 maintains activity for more than 144 h under irradiation, and the total turnover number is up to 1768. The electrochemical properties and the quenching reaction indicate the H2 generation by neutral complexes 1-4 is involved exclusively in the oxidative quenching process.

Green to blue-green-emitting cationic iridium complexes with a CF3-substituted phenyl-triazole type cyclometalating ligand: synthesis, characterization and their use for efficient light-emitting electrochemical cells.

Green to blue-green-emitting cationic iridium complexes free of sp2 C-F bonds, namely [Ir(CF3-dPhTAZ)2(bpy)]PF6 (1), [Ir(CF3-dPhTAZ)2(dmebpy)]PF6 (2) and [Ir(CF3-dPhTAZ)2(phpyim)]PF6 (3), have been designed and synthesized with 3,4-diphenyl-5-(trifluoromethyl)-4H-1,2,4-triazole (CF3-dPhTAZ) as the cyclometalating ligand (C^N) and 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (dmebpy) or 2-(1-phenyl-1H-imidazol-2-yl)pyridine (phpyim) as the ancillary ligand (N^N). In CH3CN solution, complexes 1-3 afford green to blue-green emission centered at 521, 508 and 498 nm, respectively. The electron-withdrawing CF3 group attached at the triazole ring in CF3-dPhTAZ largely blue-shifts (by over 20 nm) the emission of the complex through stabilizing the highest occupied molecular orbital. In doped films, the complexes afford sky-blue emission with near-unity phosphorescent efficiencies. In neat films, the complexes show largely suppressed phosphorescence concentration-quenching, with phosphorescent efficiencies of up to 0.66. Theoretical calculations reveal that the emission of the complexes can arise from either charge-transfer (Ir → C^N/C^N → N^N) or C^N/N^N-centered 3π-π* states, depending on the local environment of the complexes. Solid-state light-emitting electrochemical cells (LECs) based on the complexes afford green to blue-green electroluminescence centered at 525, 517 and 509 nm, respectively, with high current efficiencies of up to 35.1 cd A-1. The work reveals that CF3-dPhTAZ is a promising C^N ligand free of sp2 C-F bonds for constructing efficient cationic iridium complexes with blue-shifted emission.

Para-Substituted α-Phenyl-N-tert-butyl Nitrones: Spin-Trapping, Redox and Neuroprotective Properties.

In this work, a series of para-substituted α-phenyl-N-tert-butyl nitrones (PBN) were studied. Their radical-trapping properties were evaluated by electron paramagnetic resonance, with 4-CF3-PBN being the fastest derivative to trap the hydroxymethyl radical (•CH2OH). The redox properties of the nitrones were further investigated by cyclic voltammetry, and 4-CF3-PBN was the easiest to reduce and the hardest to oxidize. This is due to the presence of the electron-withdrawing CF3 group. Very good correlations between the Hammett constants (σp) of the substituents and both spin-trapping rates and redox potentials were observed. These correlations were further supported by computationally determined ionization potentials and atom charge densities. Finally, the neuroprotective effect of these derivatives was studied using two different in vitro models of cell death on primary cortical neurons injured by glutamate exposure or on glial cells exposed to tBuOOH. Trends between the protection afforded by the nitrones and their lipophilicity were observed. 4-CF3-PBN was the most potent agent against tBuOOH-induced oxidative stress on glial cells, while 4-Me2N-PBN showed potency in both models.

Visible-Light-Driven Anti-Markovnikov Hydrocarboxylation of Acrylates and Styrenes with CO 2

Light-driven carbon dioxide (CO2) capture and utilization is one of the most fundamental reactions in Nature. Herein, we report the first visible-light-driven photocatalyst-free hydrocarboxylation ...

Structure-Activity Relationships for the Anaesthetic and Analgaesic Properties of Aromatic Ring-Substituted Ketamine Esters.

A series of benzene ring substituted ketamine N-alkyl esters were prepared from the corresponding substituted norketamines. Few of the latter have been reported since they have not been generally accessible via known routes. We report a new general route to many of these norketamines via the Neber (oxime to α-aminoketone) rearrangement of readily available substituted 2-phenycyclohexanones. We explored the use of the substituents Cl, Me, OMe, CF3, and OCF3, with a wide range of lipophilic and electronic properties, at all available benzene ring positions. The 2- and 3-substituted compounds were generally more active than 4-substituted compounds. The most generally acceptable substituent was Cl, while the powerful electron-withdrawing substituents CF3 and OCF3 provided fewer effective analogues.

Highly Diastereoselective Anodic Fluorination of Organosulfur Compounds Based on Neighboring Participation

Highly diastereoselective and efficient anodic α-fluorination of phenyl, p-chlorophenyl, and 2-naphthyl 3,3,3-trifluoro-2-methoxypropyl sulfides was successfully carried out at platinum electrodes in Et3N-nHF (n = 3-5)/MeCN to provide the corresponding α-fluorinated products in good yields, whereas the corresponding p-methoxyphenyl sulfide derivative gave much lower diastereoselectivity. On the basis of such marked substituent effects on the diastereoselectivity and a previous study of anodic methoxylation of related sulfides,1) as well as the X-ray analysis of the configuration of the major diastereomer of the electrochemically fluorinated alph-naphthyl derivative, it was clarified that the high diastereoselectivity is attributable to the neighboring MeO group participation to the anodically generated cationic intermediate destabilized by an electron-withdrawing CF3 group.2)

Synthesis of 12-Membered Tetra-aza Macrocyclic Pyridinophanes Bearing Electron-Withdrawing Groups.

The number of substituted pyridine pyridinophanes found in the literature is limited due to challenges associated with 12-membered macrocycle and modified pyridine synthesis. Most notably, the electrophilic character at the 4-position of pyridine in pyridinophanes presents a unique challenge for introducing electrophilic chemical groups. Likewise, of the few reported, most substituted pyridine pyridinophanes in the literature are limited to electron-donating functionalities. Herein, new synthetic strategies for four new macrocycles bearing the electron-withdrawing groups CN, Cl, NO2, and CF3 are introduced. Potentiometric titrations were used to determine the protonation constants of the new pyridinophanes. Further, the influence of such modifications on the chemical behavior is predicted by comparing the potentiometric results to previously reported systems. X-ray diffraction analysis of the 4-Cl substituted species and its Cu(II) complex are also described to demonstrate the metal binding nature of these ligands. DFT analysis is used to support the experimental findings through energy calculations and ESP maps. These new molecules serve as a foundation to access a range of new pyridinophane small molecules and applications in future work.

Theoretical predication of Diels-Alder reactions of highly strained dienophiles

Using density functional theory M06-2X functional in combination with 6-311++G** basis set, we have obtained six types of highly strained dienophiles (1-6). The Diels-Alder reactions of 1-6 with butadiene (A), cyclopentadiene (B) and 3,6-bis(trifluoromethyl)-tetrazine (C) have been investigated. Calculated results show that these Diels-Alder reactions are both thermodynamically and kinetically feasible. The endo Diels-Alder reactions of 1-6 with A and B are more favorable than their exo Diels-Alder reactions, which originates from the distortion energy differences of A and B. The low activation energy of the Diels-Alder reactions of 1-6 with C arises from the electron-withdrawing group CF3 in C, which is consistent with the previous results (J. Am. Chem. Soc. 2013, 135, 15642). The Diels-Alder reactions of 1-6 with the three dienes give a family of novel propellanes but not six-membered carbocycles.