Applications of Transition Metal-Catalyzed ortho-Fluorine-Directed C-H Functionalization of (Poly)fluoroarenes in Organic Synthesis.

The synthesis of organic compounds efficiently via fewer steps but in higher yields is desirable as this reduces energy and reagent use, waste production, and thus environmental impact as well as cost. The reactivity of C-H bonds ortho to fluorine substituents in (poly)fluoroarenes with metal centers is enhanced relative to meta and para positions. Thus, direct C-H functionalization of (poly)fluoroarenes without prefunctionalization is becoming a significant area of research in organic chemistry. Novel and selective methodologies to functionalize (poly)fluorinated arenes by taking advantage of the reactivity of C-H bonds ortho to C-F bonds are continuously being developed. This review summarizes the reasons for the enhanced reactivity and the consequent developments in the synthesis of valuable (poly)fluoroarene-containing organic compounds.

Electronic Structure and Photophysics of Low Spin d5 Metallocenes.

The electronic structure and photophysics of two low spin metallocenes, decamethylmanganocene (MnCp*2) and decamethylrhenocene (ReCp*2), were investigated to probe their promise as photoredox reagents. Computational studies support the assignment of 2E2 ground state configurations and low energy ligand-to-metal charge transfer transitions for both complexes. Weak emission is observed at room temperature for ReCp*2 with τ = 1.8 ns in pentane, whereas MnCp*2 is not emissive. Calculation of the excited state reduction potentials for both metallocenes reveal their potential potency as excited state reductants (E°'([MnCp*2]+/0*) = -3.38 V and E°'([ReCp*2]+/0*) = -2.61 V vs Fc+/0). Comparatively, both complexes exhibit mild potentials for photo-oxidative processes (E°'([MnCp*2]0*/-) = -0.18 V and E°'([ReCp*2]0*/-) = -0.20 V vs Fc+/0). These results showcase the rich electronic structure of low spin d5 metallocenes and their promise as excited state reductants.

Opening a Pandora's Flask on a Prototype Catalytic Direct Arylation Reaction of Pentafluorobenzene: The Ag2CO3/Pd(OAc)2/PPh3 System.

Direct C-H functionalization reactions have opened new avenues in catalysis, removing the need for prefunctionalization of at least one of the substrates. Although C-H functionalization catalyzed by palladium complexes in the presence of a base is generally considered to proceed by the CMD/AMLA-6 mechanism, recent research has shown that silver(I) salts, frequently used as bases, can function as C-H bond activators instead of (or in addition to) palladium(II). In this study, we examine the coupling of pentafluorobenzene 1 to 4-iodotoluene 2a (and its analogues) to form 4-(pentafluorophenyl)toluene 3a catalyzed by palladium(II) acetate with the commonplace PPh3 ligand, silver carbonate as base, and DMF as solvent. By studying the reaction of 1 with Ag2CO3/PPh3 and with isolated silver (triphenylphosphine) carbonate complexes, we show the formation of C-H activation products containing the Ag(C6F5)(PPh3)n unit. However, analysis is complicated by the lability of the Ag-PPh3 bond and the presence of multiple species in the solution. The speciation of palladium(II) is investigated by high-resolution-MAS NMR (chosen for its suitability for suspensions) with a substoichiometric catalyst, demonstrating the formation of an equilibrium mixture of Pd(Ar)(κ1-OAc)(PPh3)2 and [Pd(Ar)(µ-OAc)(PPh3)]2 as resting states (Ar = Ph, 4-tolyl). These two complexes react stoichiometrically with 1 to form coupling products. The catalytic reaction kinetics is investigated by in situ IR spectroscopy revealing a two-term rate law and dependence on [Pdtot/nPPh3]0.5 consistent with the dissociation of an off-cycle palladium dimer. The first term is independent of [1], whereas the second term is first order in [1]. The observed rates are very similar with Pd(PPh3)4, Pd(Ph)(κ1-OAc)(PPh3)2, and [Pd(Ph)(µ-OAc)(PPh3)]2 catalysts. The kinetic isotope effect varied significantly according to conditions. The multiple speciation of both AgI and PdII acts as a warning against specifying the catalytic cycles in detail. Moreover, the rapid dynamic interconversion of AgI species creates a level of complexity that has not been appreciated previously.

Solution and solid-state studies of hydrogen and halogen bonding with N-heterocyclic carbene supported nickel(II) fluoride complexes.

Nickel fluoride complexes of the type [Ni(F)(L)2(ArF)] (L = phosphine, ArF = fluorinated arene) are well-known to form strong halogen and hydrogen bonds in solution and in the solid state. A comprehensive study of such non-covalent interactions using bis(carbene) complexes as acceptors and suitable halogen and hydrogen bond donors is presented. In solution, the complex [Ni(F)(iPr2Im)2(C6F5)] forms halogen and hydrogen bonds with iodopentafluorobenzene and indole, respectively, which have formation constants (K300) an order of magnitude greater than those of structurally related phosphine supported nickel fluorides. Co-crystallisation of this complex and its backbone-methylated analogue [Ni(F)(iPr2Me2Im)2(C6F5)] with 1,4-diiodotetrafluorobenzene produces halogen bonding adducts which were characterised by X-ray analysis and 19F MAS solid state NMR analysis. Differences in the chemical shifts between the nickel fluoride and its halogen bonding adduct are well in line with data that were obtained from titration studies in solution.

Solid-State 19F NMR Chemical Shift in Square-Planar Nickel-Fluoride Complexes Linked by Halogen Bonds.

The halogen bond (XB) is a highly directional class of noncovalent interactions widely explored by experimental and computational studies. However, the NMR signature of the XB has attracted limited attention. The prediction and analysis of the solid-state NMR (SSNMR) chemical shift tensor provide useful strategies to better understand XB interactions. In this work, we employ a computational protocol for modeling and analyzing the 19F SSNMR chemical shifts previously measured in a family of square-planar trans NiII-L2-iodoaryl-fluoride (L = PEt3) complexes capable of forming self-complementary networks held by a NiF···I(C) halogen bond [Thangavadivale, V.; Chem. Sci. 2018, 9, 3767-3781]. To understand how the 19F NMR resonances of the nickel-bonded fluoride are affected by the XB, we investigate the origin of the shielding in trans-[NiF(2,3,5,6-C6F4I)(PEt3)2], trans-[NiF(2,3,4,5-C6F4I)(PEt3)2], and trans-[NiF(C6F5)(PEt3)2] in the solid state, where a XB is present in the two former systems but not in the last. We perform the 19F NMR chemical shift calculations both in periodic and molecular models. The results show that the crystal packing has little influence on the NMR signatures of the XB, and the NMR can be modeled successfully with a pair of molecules interacting via the XB. Thus, the observed difference in chemical shift between solid-state and solution NMR can be essentially attributed to the XB interaction. The very high shielding of the fluoride and its driving contributor, the most shielded component of the chemical shift tensor, are well reproduced at the 2c-ZORA level. Analysis of the factors controlling the shielding shows how the highest occupied Ni/F orbitals shield the fluoride in the directions perpendicular to the Ni-F bond and specifically perpendicular to the coordination plane. This shielding arises from the magnetic coupling of the Ni(3d)/F(2p lone pair) orbitals with the vacant σNi-F* orbital, thereby rationalizing the very highly upfield (shielded) resonance of the component (δ33) along this direction. We show that these features are characteristic of square-planar nickel-fluoride complexes. The deshielding of the fluoride in the halogen-bonded systems is attributed to an increase in the energy gap between the occupied and vacant orbitals that are mostly responsible for the paramagnetic terms, notably along the most shielded direction.

Photochemistry of transition metal carbonyls.

The purpose of this Tutorial Review is to outline the fundamental photochemistry of metal carbonyls, and to show how the advances in technology have increased our understanding of the detailed mechanisms, particularly how relatively simple experiments can provide deep understanding of complex problems. We recall some important early experiments that demonstrate the key principles underlying current research, concentrating on the binary carbonyls and selected substituted metal carbonyls. At each stage, we illustrate with examples from recent applications. This review first considers the detection of photochemical intermediates in three environments: glasses and matrices; gas phase; solution. It is followed by an examination of the theory underpinning these observations. In the final two sections, we briefly address applications to the characterization and behaviour of complexes with very labile ligands such as N2, H2 and alkanes, concentrating on key mechanistic points, and also describe some principles and examples of photocatalysis.

Metathesis by Partner Interchange in σ-Bond Ligands: Expanding Applications of the σ-CAM Mechanism.

In 2007 two of us defined the σ-Complex Assisted Metathesis mechanism (Perutz and Sabo-Etienne, Angew. Chem. Int. Ed. 2007, 46, 2578-2592), that is, the σ-CAM concept. This new approach to reaction mechanisms brought together metathesis reactions involving the formation of a variety of metal-element bonds through partner-interchange of σ-bond complexes. The key concept that defines a σ-CAM process is a single transition state for metathesis that is connected by two intermediates that are σ-bond complexes while the oxidation state of the metal remains constant in precursor, intermediates and product. This mechanism is appropriate in situations where σ-bond complexes have been isolated or computed as well-defined minima. Unlike several other mechanisms, it does not define the nature of the transition state. In this review, we highlight advances in the characterization and dynamic rearrangements of σ-bond complexes, most notably alkane and zincane complexes, but also different geometries of silane and borane complexes. We set out a selection of catalytic and stoichiometric examples of the σ-CAM mechanism that are supported by strong experimental and/or computational evidence. We then draw on these examples to demonstrate that the scope of the σ-CAM mechanism has expanded to classes of reaction not envisaged in 2007 (additional σ-bond ligands, agostic complexes, sp2 -carbon, surfaces). Finally, we provide a critical comparison to alternative mechanisms for metathesis of metal-element bonds.

Electrocatalytic Proton Reduction by a Cobalt(III) Hydride Complex with Phosphinopyridine PN Ligands.

Cobalt complexes with 2-(diisopropylphosphinomethyl)pyridine (PN) ligands have been synthesized with the aim of demonstrating electrocatalytic proton reduction to dihydrogen with a well-defined hydride complex of an Earth-abundant metal. Reactions of simple cobalt precursors with 2-(diisopropylphosphino-methyl)pyridine (PN) yield [CoII(PN)2(MeCN)][BF4]2 1, [CoIII(PN)2(H)(MeCN)][PF6]2 2, and [CoIII(PN)2(H)(Cl)][PF6] 3. Complexes 1 and 3 have been characterized crystallographically. Unusually for a bidentate PN ligand, all three exhibit geometries with mutually trans phosphorus and nitrogen ligands. Complex 1 exhibits a distorted square-pyramidal geometry with an axial MeCN ligand in a low-spin electronic state. In complexes 2 and 3, the PN ligands lie in a plane leaving the hydride trans to MeCN or chloride, respectively. The redox behavior of the three complexes has been studied by cyclic voltammetry at variable scan rates and by spectroelectrochemistry. A catalytic wave is observed in the presence of trifluoroacetic acid (TFA) at an applied potential close to the Co(II/I) couple of 1. Bulk electrolysis of 1, 2, or 3 at a potential of ca. -1.4 V vs E(Fc+/Fc) in the presence of TFA yields H2 with Faradaic yields close to 100%. A catalytic mechanism is proposed in which the pyridine moiety of a PN ligand acts as a pendant proton donor following opening of the chelate ring. Additional mechanisms may also operate, especially in the presence of high acid concentration where speciation changes.

Towards measuring reactivity on micro-to-millisecond timescales with laser pump, NMR probe spectroscopy.

We present a quantitative analysis of the timescales of reactivity that are accessible to a laser pump, NMR probe spectroscopy method using para-hydrogen induced polarisation (PHIP) and identify three kinetic regimes: fast, intermediate and slow. These regimes are defined by the relative rate of reaction, k, compared to δω, the frequency of the NMR signal oscillations associated with the coherent evolution of the hyperpolarised 1H NMR signals created after para-hydrogen (p-H2) addition during the pump-probe delay. The kinetic regimes are quantitatively defined by a NMR dephasing parameter, ε = δω/k. For the fast regime, where k ≫ δω and ε tends to zero, the observed NMR signals are not affected by the chemical evolution of the system and so only an upper bound on k can be determined. In the slow regime, where k ≪ δω and ε tends to infinity, destructive interference leads to the complete dephasing of the coherent NMR signal intensity oscillations. As a result, the observed NMR signal evolution during the pump-probe delay reflects only the chemical change of the system and NMR relaxation. Finally, in the intermediate regime, where k ∼ δω, characteristic partial dephasing of the NMR signal oscillations is predicted. In the limit where the dephasing parameter is small but non-zero, chemical evolution manifests itself as a phase shift in the NMR signal oscillation that is equal to the dephasing parameter. As this phase shift is predicted to persist for pump-probe delays much longer than the timescale of the formation of the product molecules, it provides a route to measure reactivity on micro-to-millisecond timescales through NMR detection. We predict that the most significant fundamental limitations of the accessible reaction timescales are the duration of the NMR excitation pulse (∼1 µs) and the chemical shift difference (in Hz) between the p-H2-derived protons in the product molecule.

Benchmarking of Halogen Bond Strength in Solution with Nickel Fluorides: Bromine versus Iodine and Perfluoroaryl versus Perfluoroalkyl Donors.

The energetics of halogen bond formation in solution have been investigated for a series of nickel fluoride halogen bond acceptors; trans-[NiF(2-C5 NF4 )(PEt3 )2 ] (A1), trans-[NiF{2-C5 NF3 (4-H)}(PEt3 )2 ] (A2), trans-[NiF{2-C5 NF3 (4-NMe2 )}(PEt3 )2 ] (A3) and trans-[NiF{2-C5 NF2 H(4-CF3 )}(PCy3 )2 ] (A4) with neutral organic halogen bond donors, iodopentafluorobenzene (D1), 1-iodononafluorobutane (D2) and bromopentafluorobenzene (D3), in order to establish the significance of changes from perfluoroaryl to perfluoroalkyl donors and from iodine to bromine donors. 19 F NMR titration experiments have been employed to obtain the association constants, enthalpy, and entropy for the halogen bond formed between these donor-acceptor partners in protiotoluene. For A2-A4, association constants of the halogen bonds formed with iodoperfluoroalkane (D2) are consistently larger than those obtained for analogous complexes with the iodoperfluoroarene (D1). For complexes formed with A2-A4, the strength of the halogen bond is significantly lowered upon modification of the halogen donor atom from I (in D1) to Br (in D3) (for D1: 5≤K285 ≤12 m-1 , for D3: 1.0≤K193 ≤1.6 m-1 ). The presence of the electron donating NMe2 substituent on the pyridyl ring of acceptor A3 led to an increase in -ΔH, and the association constants of the halogen bond complexes formed with D1-D3, compared to those formed by A1, A2 and A4 with the same donors.

Self-complementary nickel halides enable multifaceted comparisons of intermolecular halogen bonds: fluoride ligands vs. other halides.

The syntheses of three series of complexes designed with self-complementary motifs for formation of halogen bonds between an iodotetrafluorophenyl ligand and a halide ligand at square-planar nickel are reported, allowing structural comparisons of halogen bonding between all four halides C6F4I···X-Ni (X = F, Cl, Br, I). In the series trans-[NiX(2,3,5,6-C6F4I)(PEt3)2] 1pX and trans-[NiX(2,3,4,5-C6F4I)(PEt3)2] (X = F, Cl, Br, I) 1oX, the iodine substituent on the benzene ring was positioned para and ortho to the metal, respectively. The phosphine substituents were varied in the series, trans-[NiX(2,3,5,6-C6F4I)(PEt2Ph)2] (X = F, I) 2pX. Crystal structures were obtained for the complete series 1pX, and for 1oF, 1oCl, 1oI and 2pI. All these complexes exhibited halogen bonds in the solid state, of which 1pF exhibited unique characteristics with a linear chain, the shortest halogen bond d(C6F4I···F-Ni) = 2.655(5) Å and the greatest reduction in halogen bond distance (I···F) compared to the sum of the Bondi van der Waals radii, 23%. The remaining complexes form zig-zag chains of halogen bonds with distances also reduced with respect to the sum of the van der Waals radii. The magnitude of the reductions follow the pattern F > Cl ∼ Br > I, 1pX > 1oX, consistent with the halogen bond strength following the same order. The variation in the I···X-Ni angles is consistent with the anisotropic charge distribution of the halide ligand. The temperature dependence of the X-ray structure of 1pF revealed a reduction in halogen bond distance of 0.055(7) Å on cooling from 240 to 111 K. Comparison of three polymorphs of 1oI shows that the halogen bond geometry may be altered significantly by the crystalline environment. The effect of the halogen bond on the 19F NMR chemical shift in the solid state is demonstrated by comparison of the magic-angle spinning NMR spectra of 1pF and 1oF with that of a complex incapable of halogen bond formation, trans-[NiF(C6F5)(PEt3)2] 3F. Halogen bonding causes deshielding of δiso in the component of the tensor perpendicular to the nickel coordination plane. The results demonstrate the potential of fluoride ligands for formation of halogen bonds in supramolecular structures.

Hydrogen bonding vs. halogen bonding: the solvent decides.

Control of intermolecular interactions is integral to harnessing self-assembly in nature. Here we demonstrate that control of the competition between hydrogen bonds and halogen bonds, the two most highly studied directional intermolecular interactions, can be exerted by choice of solvent (polarity) to direct the self-assembly of co-crystals. Competitive co-crystal formation has been investigated for three pairs of hydrogen bond and halogen bond donors, which can compete for a common acceptor group. These competitions have been examined in seven different solvents. Product formation has been determined and phase purity has been examined by analysis of powder X-ray diffraction patterns. Formation of hydrogen-bonded co-crystals is favoured from less polar solvents and halogen-bonded co-crystals from more polar solvents. The solvent polarity at which the crystal formation switches from hydrogen-bond to halogen-bond dominance depends on the relative strengths of the interactions, but is not a function of the solution-phase interactions alone. The results clearly establish that an appreciation of solvent effects is critical to obtain control of the intermolecular interactions.

Selectivity of C-H Activation and Competition between C-H and C-F Bond Activation at Fluorocarbons.

Partially fluorinated alkanes, arenes, and alkenes can be transformed by a variety of transition metal and lanthanide systems. Although the C-H bond is weaker than the C-F bond regardless of the hybridization of the carbon, the reaction of the C-F bond at the metal is usually more exothermic than the corresponding reaction of the C-H bonds. Both bonds are activated by the metal systems, but the preference for activating these bonds depends on the nature of the hydrocarbon and of the metal system, so that the reaction can be directed exclusively toward C-H or C-F bonds or yield a mixture of products. Additionally, the presence of fluorine differentiates between C-H bonds at different positions resulting in regioselective C-H bond activation; paradoxically, the strongest C-H bond reacts preferentially. The purpose of this review is to describe the field of reactions of partially fluorinated substrates with transition metal atoms, ions, and molecular complexes. The controlling physical properties (thermodynamics and kinetics) are described first, followed by a description of stoichiometric reactions, with the competition between the C-H and C-F activations as focus. A few representative catalytic systems are discussed. The review also highlights the benefit of combining experimental and theoretical studies.

Coherent evolution of parahydrogen induced polarisation using laser pump, NMR probe spectroscopy: Theoretical framework and experimental observation.

We recently reported a pump-probe method that uses a single laser pulse to introduce parahydrogen (p-H2) into a metal dihydride complex and then follows the time-evolution of the p-H2-derived nuclear spin states by NMR. We present here a theoretical framework to describe the oscillatory behaviour of the resultant hyperpolarised NMR signals using a product operator formalism. We consider the cases where the p-H2-derived protons form part of an AX, AXY, AXYZ or AA'XX' spin system in the product molecule. We use this framework to predict the patterns for 2D pump-probe NMR spectra, where the indirect dimension represents the evolution during the pump-probe delay and the positions of the cross-peaks depend on the difference in chemical shift of the p-H2-derived protons and the difference in their couplings to other nuclei. The evolution of the NMR signals of the p-H2-derived protons, as well as the transfer of hyperpolarisation to other NMR-active nuclei in the product, is described. The theoretical framework is tested experimentally for a set of ruthenium dihydride complexes representing the different spin systems. Theoretical predictions and experimental results agree to within experimental error for all features of the hyperpolarised 1H and 31P pump-probe NMR spectra. Thus we establish the laser pump, NMR probe approach as a robust way to directly observe and quantitatively analyse the coherent evolution of p-H2-derived spin order over micro-to-millisecond timescales.

Light-Induced Activation of a Molybdenum Oxotransferase Model within a Ru(II)-Mo(VI) Dyad.

Nature uses molybdenum-containing enzymes to catalyze oxygen atom transfer (OAT) from water to organic substrates. In these enzymes, the two electrons that are released during the reaction are rapidly removed, one at a time, by spatially separated electron transfer units. Inspired by this design, a Ru(II)-Mo(VI) dyad was synthesized and characterized, with the aim of accelerating the rate-determining step in the cis-dioxo molybdenum-catalyzed OAT cycle, the transfer of an oxo ligand to triphenyl phosphine, via a photo-oxidation process. The dyad consists of a photoactive bis(bipyridyl)-phenanthroline ruthenium moiety that is covalently linked to a bioinspired cis-dioxo molybdenum thiosemicarbazone complex. The quantum yield and luminescence lifetimes of the dyad [Ru(bpy)2(L2)MoO2(solv)]2+ were determined. The major component of the luminescence decay in MeCN solution (τ = 1149 ± 2 ns, 67%) corresponds closely to the lifetime of excited [Ru(bpy)2(phen-NH2)]2+, while the minor component (τ = 320 ± 1 ns, 31%) matches that of [Ru(bpy)2(H2-L2)]2+. In addition, the (spectro)electrochemical properties of the system were investigated. Catalytic tests showed that the dyad-catalyzed OAT from dimethyl sulfoxide to triphenyl phosphine proceeds significantly faster upon irradiation with visible light than in the dark. Methylviologen acts as a mediator in the photoredox cycle, but it is regenerated and hence only required in stoichiometric amounts with respect to the catalyst rather than sacrificial amounts. It is proposed that oxidative quenching of the photoexcited Ru unit, followed by intramolecular electron transfer, leads to the production of a reactive one-electron oxidized catalyst, which is not accessible by electrochemical methods. A significant, but less pronounced, rate enhancement was observed when an analogous bimolecular system was tested, indicating that intramolecular electron transfer between the photosensitizer and the catalytic center is more efficient than intermolecular electron transfer between the separate components.

Platinum(0)-mediated C-O bond activation of ethers via an SN2 mechanism.

A computational study of the C(methyl)-O bond activation of fluorinated aryl methyl ethers by a platinum(0) complex Pt(PCyp3)2 (Cyp = cyclopentyl) (N. A. Jasim, R. N. Perutz, B. Procacci and A. C. Whitwood, Chem. Commun., 2014, 50, 3914) demonstrates that the reaction proceeds via an SN2 mechanism. Nucleophilic attack of Pt(0) generates an ion pair consisting of a T-shaped platinum cation with an agostic interaction with a cyclopentyl group and a fluoroaryloxy anion. This ion-pair is converted to a 4-coordinate Pt(ii) product trans-[PtMe(OArF)(PCyp3)2]. Structure-reactivity correlations are fully consistent with this mechanism. The Gibbs energy of activation is calculated to be substantially higher for aryl methyl ethers without fluorine substituents and higher still for alkyl methyl ethers. These conclusions are in accord with the experimental results. Further support was obtained in an experimental study of the reaction of Pt(PCy3)2 with 2,3,5,6-tetrafluoro-4-allyloxypyridine yielding the salt of the Pt(η3-allyl) cation and the tetrafluoropyridinolate anion [Pt(PCy3)2(η3-allyl)][OC5NF4]. The calculated activation energy for this reaction is significantly lower than that for fluorinated aryl methyl ethers.