Iridium Cyclooctene Complex That Forms a Hyperpolarization Transfer Catalyst before Converting to a Binuclear C–H Bond Activation Product Responsible for Hydrogen Isotope Exchange

[IrCl­(COE)₂]₂ (<b>1</b>) reacts with pyridine (py) and H₂ to form crystallographically characterized IrCl­(H)₂(COE)­(py)₂ (<b>2</b>). <b>2</b> undergoes py loss to form 16-electron IrCl­(H)₂(COE)­(py) (<b>3</b>), with equivalent hydride ligands. When this reaction is studied with parahydrogen, <b>1</b> efficiently achieves hyperpolarization of free py (and nicotinamide, nicotine, 5-aminopyrimidine, and 3,5-lutudine) via signal amplification by reversible exchange (SABRE) and hence reflects a simple and readily available precatayst for this process. <b>2</b> reacts further over 48 h at 298 K to form crystallographically characterized (Cl)­(H)­(py)­(μ-Cl)­(μ-H)­(κ-μ-NC₅H₄)­Ir­(H)­(py)₂ (<b>4</b>). This dimer is active in the hydrogen isotope exchange process that is used in radiopharmaceutical preparations. Furthermore, while [Ir­(H)₂(COE)­(py)₃]­PF₆ (<b>6</b>) forms upon the addition of AgPF₆ to <b>2</b>, its stability precludes its efficient involvement in SABRE

Iridium Cyclooctene Complex That Forms a Hyperpolarization Transfer Catalyst before Converting to a Binuclear C–H Bond Activation Product Responsible for Hydrogen Isotope Exchange

[IrCl­(COE)₂]₂ (<b>1</b>) reacts with pyridine (py) and H₂ to form crystallographically characterized IrCl­(H)₂(COE)­(py)₂ (<b>2</b>). <b>2</b> undergoes py loss to form 16-electron IrCl­(H)₂(COE)­(py) (<b>3</b>), with equivalent hydride ligands. When this reaction is studied with parahydrogen, <b>1</b> efficiently achieves hyperpolarization of free py (and nicotinamide, nicotine, 5-aminopyrimidine, and 3,5-lutudine) via signal amplification by reversible exchange (SABRE) and hence reflects a simple and readily available precatayst for this process. <b>2</b> reacts further over 48 h at 298 K to form crystallographically characterized (Cl)­(H)­(py)­(μ-Cl)­(μ-H)­(κ-μ-NC₅H₄)­Ir­(H)­(py)₂ (<b>4</b>). This dimer is active in the hydrogen isotope exchange process that is used in radiopharmaceutical preparations. Furthermore, while [Ir­(H)₂(COE)­(py)₃]­PF₆ (<b>6</b>) forms upon the addition of AgPF₆ to <b>2</b>, its stability precludes its efficient involvement in SABRE

Iridium Cyclooctene Complex That Forms a Hyperpolarization Transfer Catalyst before Converting to a Binuclear C–H Bond Activation Product Responsible for Hydrogen Isotope Exchange

[IrCl­(COE)₂]₂ (<b>1</b>) reacts with pyridine (py) and H₂ to form crystallographically characterized IrCl­(H)₂(COE)­(py)₂ (<b>2</b>). <b>2</b> undergoes py loss to form 16-electron IrCl­(H)₂(COE)­(py) (<b>3</b>), with equivalent hydride ligands. When this reaction is studied with parahydrogen, <b>1</b> efficiently achieves hyperpolarization of free py (and nicotinamide, nicotine, 5-aminopyrimidine, and 3,5-lutudine) via signal amplification by reversible exchange (SABRE) and hence reflects a simple and readily available precatayst for this process. <b>2</b> reacts further over 48 h at 298 K to form crystallographically characterized (Cl)­(H)­(py)­(μ-Cl)­(μ-H)­(κ-μ-NC₅H₄)­Ir­(H)­(py)₂ (<b>4</b>). This dimer is active in the hydrogen isotope exchange process that is used in radiopharmaceutical preparations. Furthermore, while [Ir­(H)₂(COE)­(py)₃]­PF₆ (<b>6</b>) forms upon the addition of AgPF₆ to <b>2</b>, its stability precludes its efficient involvement in SABRE

Computational Studies Explain the Importance of Two Different Substituents on the Chelating Bis(amido) Ligand for Transfer Hydrogenation by Bifunctional Cp*Rh(III) Catalysts

A computational approach (DFT-B3PW91) is used to address previous experimental studies (<i>Chem. Commun.</i> <b>2009</b>, 6801) that showed that transfer hydrogenation of a cyclic imine by Et₃N·HCO₂H in dichloromethane catalyzed by 16-electron bifunctional Cp*Rh^III­(XNC₆H₄NX′) is faster when XNC₆H₄NX′ = TsNC₆H₄NH than when XNC₆H₄NX′ = HNC₆H₄NH or TsNC₆H₄NTs (Cp* = η⁵-C₅Me₅, Ts = toluenesulfonyl). The computational study also considers the role of the formate complex observed experimentally at low temperature. Using a model of the experimental complex in which Cp* is replaced by Cp and Ts by benzenesulfonyl (Bs), the calculations for the systems in gas phase reveal that dehydrogenation of formic acid generates CpRh^IIIH­(XNC₆H₄NX′H) via an outer-sphere mechanism. The 16-electron Rh complex + formic acid are shown to be at equilibrium with the formate complex, but the latter lies outside the pathway for dehydrogenation. The calculations reproduce the experimental observation that the transfer hydrogenation reaction is fastest for the nonsymmetrically substituted complex CpRh^III­(XNC₆H₄NX′) (X = Bs and X′ = H). The effect of the linker between the two N atoms on the pathway is also considered. The Gibbs energy barrier for dehydrogenation of formic acid is calculated to be much lower for CpRh^III­(XNCHPhCHPhNX′) than for CpRh^III­(XNC₆H₄NX′) for all combinations of X and X′. The energy barrier for hydrogenation of the imine by the rhodium hydride complex is much higher than the barrier for hydride transfer to the corresponding iminium ion, in agreement with mechanisms proposed for related systems on the basis of experimental data. Interpretation of the results by MO and NBO analyses shows that the most reactive catalyst for dehydrogenation of formic acid contains a localized Rh–NH π-bond that is associated with the shortest Rh–N distance in the corresponding 16-electron complex. The asymmetric complex CpRh^III(BsNC₆H₄NH) is shown to generate a good bifunctional catalyst for transfer hydrogenation because it combines an electrophilic metal center and a nucleophilic NH group

Computational Studies Explain the Importance of Two Different Substituents on the Chelating Bis(amido) Ligand for Transfer Hydrogenation by Bifunctional Cp*Rh(III) Catalysts

A computational approach (DFT-B3PW91) is used to address previous experimental studies (<i>Chem. Commun.</i> <b>2009</b>, 6801) that showed that transfer hydrogenation of a cyclic imine by Et₃N·HCO₂H in dichloromethane catalyzed by 16-electron bifunctional Cp*Rh^III­(XNC₆H₄NX′) is faster when XNC₆H₄NX′ = TsNC₆H₄NH than when XNC₆H₄NX′ = HNC₆H₄NH or TsNC₆H₄NTs (Cp* = η⁵-C₅Me₅, Ts = toluenesulfonyl). The computational study also considers the role of the formate complex observed experimentally at low temperature. Using a model of the experimental complex in which Cp* is replaced by Cp and Ts by benzenesulfonyl (Bs), the calculations for the systems in gas phase reveal that dehydrogenation of formic acid generates CpRh^IIIH­(XNC₆H₄NX′H) via an outer-sphere mechanism. The 16-electron Rh complex + formic acid are shown to be at equilibrium with the formate complex, but the latter lies outside the pathway for dehydrogenation. The calculations reproduce the experimental observation that the transfer hydrogenation reaction is fastest for the nonsymmetrically substituted complex CpRh^III­(XNC₆H₄NX′) (X = Bs and X′ = H). The effect of the linker between the two N atoms on the pathway is also considered. The Gibbs energy barrier for dehydrogenation of formic acid is calculated to be much lower for CpRh^III­(XNCHPhCHPhNX′) than for CpRh^III­(XNC₆H₄NX′) for all combinations of X and X′. The energy barrier for hydrogenation of the imine by the rhodium hydride complex is much higher than the barrier for hydride transfer to the corresponding iminium ion, in agreement with mechanisms proposed for related systems on the basis of experimental data. Interpretation of the results by MO and NBO analyses shows that the most reactive catalyst for dehydrogenation of formic acid contains a localized Rh–NH π-bond that is associated with the shortest Rh–N distance in the corresponding 16-electron complex. The asymmetric complex CpRh^III(BsNC₆H₄NH) is shown to generate a good bifunctional catalyst for transfer hydrogenation because it combines an electrophilic metal center and a nucleophilic NH group

Improving the Hyperpolarization of ³¹P Nuclei by Synthetic Design

Traditional ³¹P NMR or MRI measurements suffer from low sensitivity relative to ¹H detection and consequently require longer scan times. We show here that hyperpolarization of ³¹P nuclei through reversible interactions with <i>para</i>hydrogen can deliver substantial signal enhancements in a range of regioisomeric phosphonate esters containing a heteroaromatic motif which were synthesized in order to identify the optimum molecular scaffold for polarization transfer. A 3588-fold ³¹P signal enhancement (2.34% polarization) was returned for a partially deuterated pyridyl substituted phosphonate ester. This hyperpolarization level is sufficient to allow single scan ³¹P MR images of a phantom to be recorded at a 9.4 T observation field in seconds that have signal-to-noise ratios of up to 94.4 when the analyte concentration is 10 mM. In contrast, a 12 h 2048 scan measurement under standard conditions yields a signal-to-noise ratio of just 11.4. ³¹P-hyperpolarized images are also reported from a 7 T preclinical scanner

Iridium(III) Hydrido N‑Heterocyclic Carbene–Phosphine Complexes as Catalysts in Magnetization Transfer Reactions

The hyperpolarization (HP) method signal amplification by reversible exchange (SABRE) uses <i>para</i>-hydrogen to sensitize substrate detection by NMR. The catalyst systems [Ir­(H)₂(IMes)­(MeCN)₂(R)]­BF₄ and [Ir­(H)₂(IMes)­(py)₂(R)]­BF₄ [py = pyridine; R = PCy₃ or PPh₃; IMes = 1,3-bis­(2,4,6-trimethylphenyl)­imidazol-2-ylidene], which contain both an electron-donating N-heterocyclic carbene and a phosphine, are used here to catalyze SABRE. They react with acetonitrile and pyridine to produce [Ir­(H)₂(NCMe)­(py)­(IMes)­(PPh₃)]­BF₄ and [Ir­(H)₂(NCMe)­(py)­(IMes)­(PCy₃)]­BF₄, complexes that undergo ligand exchange on a time scale commensurate with observation of the SABRE effect, which is illustrated here by the observation of both pyridine and acetonitrile HP. In this study, the required symmetry breaking that underpins SABRE is provided for by the use of chemical inequivalence rather than the previously reported magnetic inequivalence. As a consequence, we show that the ligand sphere of the polarization transfer catalyst itself becomes hyperpolarized and hence that the high-sensitivity detection of a number of reaction intermediates is possible. These species include [Ir­(H)₂(NCMe)­(py)­(IMes)­(PPh₃)]­BF₄, [Ir­(H)₂(MeOH)­(py)­(IMes)­(PPh₃)]­BF₄, and [Ir­(H)₂(NCMe)­(py)₂(PPh₃)]­BF₄. Studies are also described that employ the deuterium-labeled substrates CD₃CN and C₅D₅N, and the labeled ligands P­(C₆D₅)₃ and IMes-<i>d</i>₂₂, to demonstrate that dramatically improved levels of HP can be achieved as a consequence of reducing proton dilution and hence polarization wastage. By a combination of these studies with experiments in which the magnetic field experienced by the sample at the point of polarization transfer is varied, confirmation of the resonance assignments is achieved. Furthermore, when [Ir­(H)₂(pyridine-<i>h</i>₅)­(pyridine-<i>d</i>₅)­(IMes)­(PPh₃)]­BF₄ is examined, its hydride ligand signals are shown to become visible through <i>para</i>-hydrogen-induced polarization rather than SABRE

Utilization of SABRE-Derived Hyperpolarization To Detect Low-Concentration Analytes via 1D and 2D NMR Methods

The characterization of materials by the inherently insensitive method of NMR spectroscopy plays a vital role in chemistry. Increasingly, hyperpolarization is being used to address the sensitivity limitation. Here, by reference to quinoline, we illustrate that the SABRE hyperpolarization technique, which uses <i>para</i>-hydrogen as the source of polarization, enables the rapid completion of a range of NMR measurements. These include the collection of ¹³C, ¹³C­{¹H}, and NOE data in addition to more complex 2D COSY, ultrafast 2D COSY and 2D HMBC spectra. The observations are made possible by the use of a flow probe and external sample preparation cell to re-hyperpolarize the substrate between transients, allowing repeat measurements to be made within seconds. The potential benefit of the combination of SABRE and 2D NMR methods for rapid characterization of low-concentration analytes is therefore established

Hydrogen Activation by an Aromatic Triphosphabenzene

Aromatic hydrogenation is a challenging transformation typically requiring alkali or transition metal reagents and/or harsh conditions to facilitate the process. In sharp contrast, the aromatic heterocycle 2,4,6-tri-<i>tert</i>-butyl-1,3,5-triphosphabenzene is shown to be reduced under 4 atm of H₂ to give [3.1.0]­bicylo reduction products, with the structure of the major isomer being confirmed by X-ray crystallography. NMR studies show this reaction proceeds via a reversible 1,4-H₂ addition to generate an intermediate species, which undergoes an irreversible suprafacial hydride shift concurrent with P–P bond formation to give the isolated products. Further, <i>para</i>-hydrogen experiments confirmed the addition of H₂ to triphosphabenzene is a bimolecular process. Density functional theory (DFT) calculations show that facile distortion of the planar triphosphabenzene toward a boat-conformation provides a suprafacial combination of vacant acceptor and donor orbitals that permits this direct and uncatalyzed reduction of the aromatic molecule

Competing Pathways in the Photochemistry of Ru(H)₂(CO)(PPh₃)₃

The photochemistry of Ru­(H)₂(CO)­(PPh₃)₃ (<b>1</b>) has been reinvestigated employing laser and conventional light sources in conjunction with NMR spectroscopy and IR spectroscopy. The sensitivity of NMR experiments was enhanced by use of <i>p</i>-H₂-induced polarization (PHIP), and a series of unexpected reactions were observed. The photoinduced reductive elimination of H₂ was demonstrated (a) via NMR spectroscopy by the observation of hyperpolarized <b>1</b> on pulsed laser photolysis in the presence of <i>p</i>-H₂ and (b) via nanosecond time-resolved infrared (TRIR) spectroscopy studies of the transient [Ru­(CO)­(PPh₃)₃]. Elimination of H₂ competes with photoinduced loss of PPh₃, as demonstrated by formation of dihydrogen, triphenylarsine, and pyridine substitution products which are detected by NMR spectroscopy. The corresponding coordinatively unsaturated 16-electron intermediate [Ru­(H)₂(CO)­(PPh₃)₂] exists in two isomeric forms according to TRIR spectroscopy that react with H₂ and with pyridine on a nanosecond time scale. These two pathways, reductive elimination of H₂ and PPh₃ loss, are shown to occur with approximately equal quantum yields upon 355 nm irradiation. Low-temperature photolysis in the presence of H₂ reveals the formation of the dihydrogen complex Ru­(H)₂(η²-H₂)­(CO)­(PPh₃)₂, which is detected by NMR and IR spectroscopy. This complex reacts further within seconds at room temperature, and its behavior provides a rationale to explain the PHIP results. Furthermore, photolysis in the presence of AsPh₃ and H₂ generates Ru­(H)₂(AsPh₃)­(CO)­(PPh₃)₂. Two isomers of Ru­(H)₂(CO)­(PPh₃)₂(pyridine) are formed according to NMR spectroscopy on initial photolysis of <b>1</b> in the presence of pyridine under H₂. Two further isomers are formed as minor products; the configuration of each isomer was identified by NMR spectroscopy. Laser pump-NMR probe spectroscopy was used to observe coherent oscillations in the magnetization of one of the isomers of the pyridine complex; the oscillation frequency corresponds to the difference in chemical shift between the hydride resonances. Pyridine substitution products were also detected by TRIR spectroscopy