Speciation and Reactivity of Mono- and Binuclear Ni Intermediates in Aminoquinoline-Directed C-H Arylation and Benzylation.

This paper describes detailed organometallic studies of the aminoquinoline-directed Ni-catalyzed C-H functionalization of 2,3,4,5-tetrafluoro-N-(quinolin-8-yl)benzamide with diaryliodonium reagents. A combination of 19F NMR spectroscopy and X-ray crystallography is used to track and characterize diamagnetic and paramagnetic intermediates throughout this transformation. These provide key insights into both the cyclometalation and oxidative functionalization steps of the catalytic cycle. The reaction conditions (solvent, ligands, base, and stoichiometry) play a central role in the observation of a NiII precyclometalation intermediate as well as in the speciation of the NiII products of C-H activation. Both mono- and binuclear cyclometalated NiII species are observed and interconvert, depending on the reaction conditions. Cyclic voltammetry reveals that the NiII/III redox potentials for the cyclometalated intermediates vary by more than 700 mV depending on their coordination environments, and these differences are reflected in their relative reactivity with diaryliodonium oxidants. The oxidative functionalization reaction affords a mixture of arylated and solvent functionalization organic products, depending on the conditions and solvent. For example, conducting oxidation in toluene leads to the preferential formation of the benzylated product. A series of experiments implicate a NiII/III/IV pathway for this transformation.

Characterization and Reactivity of Copper(II) and Copper(III) σ-Aryl Intermediates in Aminoquinoline-Directed C-H Functionalization.

Over the past decade, numerous reports have focused on the development and applications of Cu-mediated C-H functionalization reactions; however, to date, little is known about the Cu intermediates involved in these transformations. This paper details the observation and characterization of CuII and CuIII intermediates in aminoquinoline-directed C(sp2)-H functionalization of a fluoroarene substrate. An initial C(sp2)-H activation at CuII occurs at room temperature to afford an isolable anionic cyclometalated CuII complex. This complex undergoes single-electron oxidation with ferrocenium or AgI salts under mild conditions (5 min at room temperature) to afford C(sp2)-C(sp2) or C(sp2)-NO2 coupling products. Spectroscopic studies implicate the formation of a transient diamagnetic CuIII-σ-aryl intermediate that undergoes either (i) a second C(sp2)-H activation at CuIII followed by C-C bond-forming reductive elimination or (ii) reaction with a NO2- nucleophile and C(sp2)-NO2 coupling.

Nickel(IV) Intermediates in Aminoquinoline-Directed C(sp2)-C(sp3) Coupling.

We use a ligand design strategy to isolate a cyclometalated nickel(IV) complex that is directly analogous to a key intermediate proposed in aminoquinoline-directed C-H functionalization catalysis. This nickel(IV) complex is formed by oxidative addition of a diaryliodonium reagent to an anionic nickel(II)-picolinate precursor. The nickel(IV) σ-aryl complex is stable at room temperature but undergoes C(sp2)-C(sp3) bond-forming reductive elimination under mild conditions (70 °C, 120 min). Overall, this study demonstrates the accessibility of long-sought-after nickel(IV) intermediates in C-H functionalization catalysis. Furthermore, it demonstrates that LX-type (bidentate, mono-anionic) ligands such as picolinate dramatically stabilize these nickel(IV) species.

Distortion of the [FeNO]2 Core in Flavodiiron Nitric Oxide Reductase Models Inhibits N-N Bond Formation and Promotes Formation of Unusual Dinitrosyl Iron Complexes: Implications for Catalysis and Reactivity.

Flavodiiron nitric oxide reductases (FNORs) carry out the reduction of nitric oxide (NO) to nitrous oxide (N2O), allowing infectious pathogens to mitigate toxic levels of NO generated in the human immune response. We previously reported the model complex [Fe2(BPMP)(OPr)(NO)2](OTf)2 (1, OPr- = propionate) that contains two coplanar NO ligands and that is capable of quantitative NO reduction to N2O [White et al. J. Am. Chem. Soc. 2018, 140, 2562-2574]. Here we investigate, for the first time, how a distortion of the active site affects the ability of the diiron core to mediate N2O formation. For this purpose, we prepared several analogues of 1 that contain two monodentate ligands in place of the bridging carboxylate, [Fe2(BPMP)(X)2(NO)2]3+/1+ (2-X; X = triflate, 1-methylimidazole, or methanol). Structural data of 2-X show that without the bridging carboxylate, the diiron core expands, leading to elongated (O)N-N(O) distances (from 2.80 Å in 1 to 3.00-3.96 Å in 2-X) and distorted (O)N-Fe-Fe-N(O) dihedral angles (from coplanarity (5.9°) in 1 to 52.9-85.1° in 2-X). Whereas 1 produces quantitative amounts of N2O upon one-electron reduction, N2O production is substantially impeded in 2-X, to an initial 5-10% N2O yield. The main products after reduction are unprecedented hs-FeII/{Fe(NO)2}9/10 dinitrosyl iron complexes (DNICs). Even though mononuclear DNICs are stable and do not show N-N coupling (since it is a spin-forbidden process), the hs-FeII/{Fe(NO)2}9/10 DNICs obtained from 2-X show unexpected reactivity and produce up to quantitative N2O yields after 2 h. The implications of these results for the active site structure of FNORs are discussed.

Tunable Optical Molecular Thermometers Based on Metallacrowns.

The effect of ligands' energy levels on thermal dependence of lanthanide emission was examined to create new molecular nanothermometers. A series of Ln2Ga8L8'L8″ metallacrowns (shorthand Ln2L8'), where Ln = Gd3+, Tb3+, or Sm3+ (H3L' = salicylhydroxamic acid (H3shi), 5-methylsalicylhydroxamic acid (H3mshi), 5-methoxysalicylhydroxamic acid (H3moshi), and 3-hydroxy-2-naphthohydroxamic acid (H3nha)) and H2L″ = isophthalic acid (H2iph), was synthesized and characterized. Within the series, ligand-centered singlet state (S1) energy levels ranged from 23,300 to 27,800 cm-1, while triplet (T1) energy levels ranged from 18,150 to 21,980 cm-1. We demonstrated that the difference between T1 levels and relevant energies of the excited 4G5/2 level of Sm3+ (17,800 cm-1) and 5D4 level of Tb3+ (20,400 cm-1) is the major parameter controlling thermal dependence of the emission intensity via the back energy transfer mechanism. However, when the energy difference between S1 and T1 levels is small (below 3760 cm-1), the S1 → T1 intersystem crossing (and its reverse, S1 ← T1) mechanism contributes to the thermal behavior of metallacrowns. Both mechanisms affect Ln3+-centered room-temperature quantum yields with values ranging from 2.07(6)% to 31.2(2)% for Tb2L8' and from 0.0267(7)% to 2.27(5)% for Sm2L8'. The maximal thermal dependence varies over a wide thermal range (ca. 150-350 K) based on energy gaps between relevant ligand-based and lanthanide-based electronic states. By mixing Tb2moshi8' with Sm2moshi8' in a 1:1 ratio, an optical thermometer with a relative thermal sensitivity larger than 3%/K at 225 K was created. Other temperature ranges are also accessible with this approach.

Defluorinative Functionalization of Pd(II) Fluoroalkyl Complexes.

When subjected to arylboranes, anionic trifluoromethyl and difluorobenzyl palladium(II) complexes undergo fluoride abstraction followed by 1,1-migratory insertion. The resulting intermediate fluoroalkyl species can be induced to undergo a subsequent transmetalation and reductive elimination from either an in situ formed fluoroboronate (FB(Ar3)-) or an exogenous boronic acid/ester (ArB(OR)2) and nucleophilic activator, representing a net defluorinative arylation reaction. The latter method enabled a structurally diverse substrate scope to be prepared from either an isolated palladium-CF3 complex, or from Pd(PPh3)4 and other commercially available reagents.

Iodinated Metallacrowns: Toward Combined Bimodal Near-Infrared and X-Ray Contrast Imaging Agents.

Multimodal probes capable of combining imaging modalities within a single molecule are in high demand today as they can provide information at both molecular and anatomical levels. Herein, a study was conducted on a series of gallium(III)/lanthanide(III) bis(12-MC-4) metallacrowns (MCs) with the general composition {Ln[12-MCGa III N(shi) -4]}2 (iph)4 (Ln-Ix , x=0, 4, 8, 12), where shi and iph are salicylhydroximate and isophthalate ligands, respectively, or their iodinated derivatives. For Yb-Ix , the attenuation in X-ray computed tomography (XCT) imaging and near-infrared (NIR) luminescence properties can be finely tuned by controlled structural modifications based on iodo groups. Solutions of Yb-Ix appear to be 22-40 times more efficient as XCT agents in comparison to the commercially available iobitridol, while providing an intense emission signal in the NIR range with total quantum yields up to 8.6 %, which are among the highest values reported so far. Therefore, these molecules are promising potential bimodal agents for combined NIR luminescence and XCT imaging.

Visible, Near-Infrared, and Dual-Range Luminescence Spanning the 4f Series Sensitized by a Gallium(III)/Lanthanide(III) Metallacrown Structure.

Lanthanide(III) ions (Ln3+) in coordination compounds exhibit unique luminescence properties with narrow and characteristic f-f transitions throughout the visible and near-infrared (NIR) ranges. In addition, some Ln3+ such as Pr3+, Sm3+, Dy3+, Ho3+, Er3+, and Tm3+ possess an exceptional ability, although less explored, to exhibit dual-range emissions. Such remarkable features allow highly specific use in materials science and biology, for example, for the creation of sophisticated barcode modules or for the next generation of optical imaging applications. Herein, a series of Ga3+/Ln3+ metallacrowns (MCs) with the general composition [LnGa8(shi)8(OH)4]Na·xCH3OH·yH2O (Ln-1, Ln = Pr3+, Nd3+, Sm3+-Yb3+ and analogue Y3+; H3shi = salicylhydroxamic acid) is presented. Ln-1 were obtained by reacting Ga3+ and Ln3+ nitrate salts with the H3shi ligand. X-ray single crystal unit cell analysis confirmed that all MCs are isostructural. The crystal structure was solved for the Nd3+ analogue and revealed that Nd3+ is centered between two [12-MCGaIIIN(shi)-4] MC rings and bound to eight hydroximate oxygen ions (four from each ring) in a pseudosquare antiprismatic fashion adopting a pseudo-D4h symmetry. Pulsed gradient spin echo diffusion ordered 1H NMR spectroscopy and electrospray ionization mass spectrometry confirmed that the structure of Ln-1 remains intact in methanol solutions while mass spectrometry suggests that four OH- bridges are exchanged with CH3O-/CD3O-. An exceptional ability of this series of MCs to sensitize the characteristic emission of Ln3+ was confirmed with the observation of bright red and green emission signals of Eu-1 and Tb-1, NIR emissions of Yb-1 and Nd-1, and dual-range emissions of Pr-1, Sm-1, Dy-1, Ho-1, Er-1, and Tm-1 in the solid state upon excitation into ligand-centered bands at 340 nm. The luminescence properties of Ln-1 (Ln = Nd3+, Sm3+, Eu3+, Tb3+, Dy3+, and Yb3+) were also investigated in CH3OH and CD3OD solutions. For Eu-1 and Yb-1 MCs, more extensive analyses of the photophysical properties were performed, which included the determination of radiative lifetimes, intrinsic quantum yields, and sensitization efficiencies. The absolute quantum yields (QLnL) of Ln-1 in the visible and NIR ranges have been determined. In the case of Sm-1, the values of QLnL in CH3OH and CD3OD solutions are exceptionally high, that is, 10.1(5) and 83(1) %. Values obtained for Yb-1, that is, 0.78(4) % in CH3OH and 8.4(1)% in CD3OD, are among the highest ones reported today for Yb3+ complexes formed with nondeuterated and nonhalogenated ligands.

Catalytically Relevant Intermediates in the Ni-Catalyzed C(sp2)-H and C(sp3)-H Functionalization of Aminoquinoline Substrates.

This Article describes the synthesis and characterization of cyclometalated aminoquinoline NiII σ-aryl and σ-alkyl complexes that have been proposed as key intermediates in Ni-catalyzed C-H functionalization reactions. These NiII complexes serve as competent catalysts for the C-H functionalization of aminoquinoline derivatives with I2. They also react stoichiometrically with I2 to form either aryl iodides or ß-lactams within minutes at room temperature. Furthermore, they react with AgI salts at -30 °C to afford isolable five-coordinate NiIII species. The NiIII σ-aryl complexes proved inert toward C(sp2)-I bond-forming reductive elimination under all conditions examined (up to 140 °C in DMF). In contrast, a NiIII σ-alkyl analogue underwent C(sp3)-N bond-forming reductive elimination at 140 °C in DMF to afford a ß-lactam product. However, despite the ability of this latter NiIII species to participate in stoichiometric product formation, the complex was not a competent catalyst for ß-lactam formation. Overall, these results suggest against the intermediacy of NiIII species in these C-H functionalization reactions.

Aryl-Fluoride Bond-Forming Reductive Elimination from Nickel(IV) Centers.

The treatment of pyridine- and pyrazole-ligated NiII σ-aryl complexes with Selectfluor results in C(sp2)-F bond formation under mild conditions. With appropriate design of supporting ligands, diamagnetic NiIV σ-aryl fluoride intermediates can be detected spectroscopically and/or isolated during these transformations. These studies demonstrate for the first time that NiIV σ-aryl fluoride complexes participate in challenging C(sp2)-F bond-forming reductive elimination to yield aryl fluoride products.

Connecting Organometallic Ni(III) and Ni(IV): Reactions of Carbon-Centered Radicals with High-Valent Organonickel Complexes.

This paper describes the one-electron interconversions of isolable NiIII and NiIV complexes through their reactions with carbon-centered radicals (R•). First, model NiIII complexes are shown to react with alkyl and aryl radicals to afford NiIV products. Preliminary mechanistic studies implicate a pathway involving direct addition of a carbon-centered radical to the NiIII center. This is directly analogous to the known reactivity of NiII complexes with R•, a step that is commonly implicated in catalysis. Second, a NiIV-CH3 complex is shown to react with aryl and alkyl radicals to afford C-C bonds via a proposed SH2-type mechanism. This pathway is leveraged to enable challenging H3C-CF3 bond formation under mild conditions. Overall, these investigations suggest that NiII/III/IV sequences may be viable redox pathways in high-oxidation-state nickel catalysis.

Nickel(II/IV) Manifold Enables Room-Temperature C(sp3)-H Functionalization.

This Article demonstrates a mild oxidatively induced C(sp3)-H activation at a high-valent Ni center. In contrast with most C(sp3)-H activation reactions at NiII, the transformation proceeds at room temperature and generates an isolable NiIV σ-alkyl complex. Density functional theory studies show two plausible mechanisms for this C-H activation process involving triflate-assisted C-H cleavage at either a NiIV or a NiIII intermediate. The former pathway is modestly favored over the latter (by ∼3 kcal/mol). The NiIV σ-alkyl product of C-H cleavage reacts with a variety of nucleophiles to form C(sp3)-X bonds (X = halide, oxygen, nitrogen, sulfur, or carbon). These stoichiometric transformations can be coupled using N-fluoro-2,4,6-trimethylpyridinium triflate as a terminal oxidant in conjunction with chloride as a nucleophile to achieve a proof-of-principle NiII/IV-catalyzed C(sp3)-H functionalization reaction.

Synthetic Model Complex of the Key Intermediate in Cytochrome P450 Nitric Oxide Reductase.

Fungal denitrification plays a crucial role in the nitrogen cycle and contributes to the total N2O emission from agricultural soils. Here, cytochrome P450 NO reductase (P450nor) reduces two NO to N2O using a single heme site. Despite much research, the exact nature of the critical "Intermediate I" responsible for the key N-N coupling step in P450nor is unknown. This species likely corresponds to a Fe-NHOH-type intermediate with an unknown electronic structure. Here we report a new strategy to generate a model system for this intermediate, starting from the iron(III) methylhydroxylamide complex [Fe(3,5-Me-BAFP)(NHOMe)] (1), which was fully characterized by 1H NMR, UV-vis, electron paramagnetic resonance, and vibrational spectroscopy (rRaman and NRVS). Our data show that 1 is a high-spin ferric complex with an N-bound hydroxylamide ligand that is strongly coordinated (Fe-N distance, 1.918 Å; Fe-NHOMe stretch, 558 cm-1). Simple one-electron oxidation of 1 at -80 °C then cleanly generates the first model system for Intermediate I, [Fe(3,5-Me-BAFP)(NHOMe)]+ (1+). UV-vis, resonance Raman, and Mössbauer spectroscopies, in comparison to the chloro analogue [Fe(3,5-Me-BAFP)(Cl)]+, demonstrate that 1+ is best described as an FeIII-(NHOMe)• complex with a bound NHOMe radical. Further reactivity studies show that 1+ is highly reactive toward NO, a reaction that likely proceeds via N-N bond formation, following a radical-radical-type coupling mechanism. Our results therefore provide experimental evidence, for the first time, that an FeIII-(NHOMe)• electronic structure is indeed a reasonable electronic description for Intermediate I and that this electronic structure is advantageous for P450nor catalysis because it can greatly facilitate N-N bond formation and, ultimately, N2O generation.

A Unique LnIII {[3.3.1]GaIII Metallacryptate} Series That Possesses Properties of Slow Magnetic Relaxation and Visible/Near-Infrared Luminescence.

A new family of [3.3.1] metallacryptates with the general composition [LnGa6 (H2 shi)(Hshi)(shi)7 (C5 H5 N)] (Ln-1; shi3- =salicylhydroximate; Ln = Pr, Nd, Sm-Yb) has been synthesized and characterized. Ln-1 display both interesting magnetic and luminescent properties. Sm-1 has sharp emission bands in the visible and the near-infrared (NIR) regions with quantum yield values (QSmL ) of 1.64(9) and 5.5(2). 10-2 %, respectively. Tb-1 exhibits a weak green emission (QTbL =1.89(3). 10-1 %) while Pr-1, Nd-1, Ho-1, Er-1, and Yb-1 possess emission bands in the NIR range with QPrL =3.7(2). 10-3 %, QNdL =1.71(5). 10-1 %, QHoL =1.1(2). 10-3 %, QErL =7.1(2). 10-3 % and QYbL =0.65(3) %. Nd-1, Dy-1, and Yb-1 display slow magnetization relaxation in an applied field, where only Dy-1 has been observed to follow an Orbach process (Ueff =12.7 K). The combination of NIR emission with magnetic properties makes Nd-1 and Yb-1 attractive candidates as smart materials addressable in two manners.

One-Step Assembly of Visible and Near-Infrared Emitting Metallacrown Dimers Using a Bifunctional Linker.

A family of dimeric LnIII [12-MCGa(III)N(shi) -4] metallacrowns (MCs) (LnIII =Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb) was synthesized using the isophthalate group (ip2- ) as a linker. The [LnGa4 ]2 complexes exhibit remarkable photophysical properties, with large molar absorptivities of ≈4×104 m-1 cm-1 , high quantum yields and long luminescence lifetimes with values of (i) 31.2(2)% and 1.410(1) ms, respectively for the visible-emitting [TbGa4 ]2 complex and (ii) 2.43(6)% and 30.5(1) µs for the near-infrared (NIR) emitting [YbGa4 ]2 in the solid state. The NIR emission was obtained not only from Yb, Nd, and Er complexes but also from the less frequently observed emitters such as Pr and Ho. In addition, emission in both visible and NIR domains could be detected for Dy and Sm MCs. ESI-MS and UV/Vis data revealed that the complexes are highly stable in dimethylsulfoxide (DMSO) solution with the 1 H- and COSY-NMR spectra of the diamagnetic [YGa4 ]2 analogue providing evidence for long-term solution stability. This new approach allows one to construct a basis for highly luminescent MCs that may be further modified to be adapted for applications such as optical imaging.

Oxidatively Induced C-H Activation at High Valent Nickel.

This communication describes a series of oxidatively induced intramolecular arene C-H activation reactions of NiII model complexes to yield NiIV σ-aryl products. These reactions proceed within 10 min at room temperature, which represents among the mildest conditions reported for C-H cleavage at a Ni center. A combination of density functional theory and preliminary experimental mechanistic studies implicate a pathway involving initial 2e- oxidation of the NiII starting materials by the F+ transfer reagent N-fluoro-2,4,6-trimethylpyridinium triflate followed by triflate-assisted C-H cleavage at NiIV to yield the products.

Stoichiometric and Catalytic Aryl-Perfluoroalkyl Coupling at Tri-tert-butylphosphine Palladium(II) Complexes.

This Communication describes studies of Ph-RF (RF = CF3 or CF2CF3) coupling at Pd complexes of general structure (PtBu3)PdII(Ph)(RF). The CF3 analogue participates in fast Ph-CF3 coupling (<5 min at 80 °C). However, the formation of side products limits the yield of this transformation as well as its translation to catalysis. DFT and experimental studies suggest that the side products derive from facile α-fluoride elimination at the 3-coordinate PdII complex. Furthermore, they show that this undesired pathway can be circumvented by changing from a CF3 to a CF2CF3 ligand. Ultimately, the insights gained from stoichiometric studies enabled the identification of Pd(PtBu3)2 as a catalyst for the Pd-catalyzed cross-coupling of aryl bromides with TMSCF2CF3 to afford pentafluoroethylated arenes.

Ferric Heme-Nitrosyl Complexes: Kinetically Robust or Unstable Intermediates?

We have determined a convenient method for the bulk synthesis of high-purity ferric heme-nitrosyl complexes ({FeNO}6 in the Enemark-Feltham notation); this method is based on the chemical or electrochemical oxidation of corresponding {FeNO}7 precursors. We used this method to obtain the five- and six-coordinate complexes [Fe(TPP)(NO)]+ (TPP2- = tetraphenylporphyrin dianion) and [Fe(TPP)(NO)(MI)]+ (MI = 1-methylimidazole) and demonstrate that these complexes are stable in solution in the absence of excess NO gas. This is in stark contrast to the often-cited instability of such {FeNO}6 model complexes in the literature, which is likely due to the common presence of halide impurities (although other impurities could certainly also play a role). This is avoided in our approach for the synthesis of {FeNO}6 complexes via oxidation of pure {FeNO}7 precursors. On the basis of these results, {FeNO}6 complexes in proteins do not show an increased stability toward NO loss compared to model complexes. We also prepared the halide-coordinated complexes [Fe(TPP)(NO)(X)] (X = Cl-, Br-), which correspond to the elusive, key reactive intermediate in the so-called autoreduction reaction, which is frequently used to prepare {FeNO}7 complexes from ferric precursors. All of the complexes were characterized using X-ray crystallography, UV-vis, IR, and nuclear resonance vibrational spectroscopy (NRVS). On the basis of the vibrational data, further insight into the electronic structure of these {FeNO}6 complexes, in particular with respect to the role of the axial ligand trans to NO, is obtained.

Modular Attachment of Appended Boron Lewis Acids to a Ruthenium Pincer Catalyst: Metal-Ligand Cooperativity Enables Selective Alkyne Hydrogenation.

A new series of bifunctional Ru complexes with pendent Lewis acidic boranes were prepared by late-stage modification of an active hydrogen-transfer catalyst. The appended boranes modulate the reactivity of a metal hydride as well as catalytic hydrogenations. After installing acidic auxiliary groups, the complexes become multifunctional and catalyze the cis-selective hydrogenation of alkynes with higher rates, conversions, and selectivities compared with the unmodified catalyst.