Paramagnetic Relaxation Agents for Enhancing Temporal Resolution and Sensitivity in Multinuclear FlowNMR Spectroscopy.

Sensitivity in FlowNMR spectroscopy for reaction monitoring often suffers from low levels of pre-magnetisation due to limited residence times of the sample in the magnetic field. While this in-flow effect is tolerable for high sensitivity nuclei such as 1 H and 19 F, it significantly reduces the signal-to-noise ratio in 31 P and 13 C spectra, making FlowNMR impractical for low sensititvity nuclei at low concentrations. Paramagnetic relaxation agents (PRAs), which enhance polarisation and spin-lattice relaxation, could eliminate the adverse in-flow effect and improve the signal-to-noise ratio. Herein, [Co(acac)3 ], [Mn(acac)3 ], [Fe(acac)3 ], [Cr(acac)3 ], [Ni(acac)2 ]3, [Gd(tmhd)3 ] and [Cr(tmhd)3 ] are investigated for their effectiveness in improving signal intensity per unit time in FlowNMR applications under the additional constraint of chemical inertness towards catalytically active transition metal complexes. High-spin Cr(III) acetylacetonates emerged as the most effective compounds, successfully reducing 31 P T1 values four- to five-fold at PRA concentrations as low as 10 mM without causing adverse line broadening. Whereas [Cr(acac)3 ] showed signs of chemical reactivity with a mixture of triphenylphosphine, triphenylphosphine oxide and triphenylphosphate over the course of several hours at 80° C, the bulkier [Cr(tmhd)3 ] was stable and equally effective as a PRA under these conditions. Compatibility with a range of representative transition metal complexes often used in homogeneous catalysis has been investigated, and application of [Cr(tmhd)3 ] in significantly improving 1 H and 31 P{1 H} FlowNMR data quality in a Rh-catalysed hydroformylation reaction has been demonstrated. With the PRA added, 13 C relaxation times were reduced more than six-fold, allowing quantitative reaction monitoring of substrate consumption and product formation by 13 C{1 H} FlowNMR spectroscopy at natural abundance.

Synthesis, Structure, and Reactivity of Magnesium Pentalenides.

The first magnesium pentalenide complexes have been synthesized via deprotonative metalation of 1,3,4,6-tetraphenyldihydropentalene (Ph4PnH2) with magnesium alkyls. Both the nature of the metalating agent and the reaction solvent influenced the structure of the resulting complexes, and an equilibrium between Mg[Ph4Pn] and [nBuMg]2[Ph4Pn] was found to exist and investigated by NMR, XRD, and UV-vis spectroscopic techniques. Studies on the reactivity of Mg[Ph4Pn] with water, methyl iodide, and trimethylsilylchloride revealed that the [Ph4Pn]2- unit undergoes electrophilic addition at 1,5-positions instead of 1,4-positions known for the unsubstituted pentalenide, Pn2-, highlighting the electronic influence of the four aryl substituents on the pentalenide core. The ratio of syn/anti addition was found to be dependent on the size of the incoming electrophile, with methylation yielding a 60:40 mixture, while silylation yielded exclusively the anti-isomer.

Connect Four: Tetraarylated Dihydropentalenes and Triarylated Monocyclic Pentafulvenes from Cyclopentadienes and Enones.

In search of novel pentalenide ligands for use in organometallic chemistry and homogeneous catalysis, we report the scope of a straightforward base-promoted Michael annulation of cyclopentadienes with α,ß-unsaturated ketones that allows the introduction of symmetrical as well as unsymmetrical aryl and alkyl substitution patterns including electron-donating as well as electron-withdrawing substituents. More than 16 examples of various isomers of 1,3,4,6-tetraarylated dihydropentalenes have been synthesized in isolated yields of up to 78%, representing a substantial expansion of the range of dihydropentalene scaffolds known to date. Double bond isomerization between the two pentacyclic rings in 1,2-dihydropentalenes with electronically different substituents occurred depending on the polarization of the molecule. The melting points of the air-stable dihydropentalenes decrease, and their solubilities in organic solvents improve with increasing substitution and decreasing symmetry of the molecule. A competitive pseudo-retro-aldol pathway produces 1,3,6-triarylated monocyclic pentafulvenes as side products in yields of 9-68%, which can be cleanly isolated (8 new examples) and used for other synthetic purposes, including separate cyclization to other dihydropentalenes.

Multi-nuclear, high-pressure, operando FlowNMR spectroscopic study of Rh/PPh3 - catalysed hydroformylation of 1-hexene.

The hydroformylation of 1-hexene with 12 bar of 1 : 1 H2/CO in the presence of the catalytic system [Rh(acac)(CO)2]/PPh3 was successfully studied by real-time multinuclear high-resolution FlowNMR spectroscopy at 50 °C. Quantitative reaction progress curves that yield rates as well as chemo- and regioselectivities have been obtained with varying P/Rh loadings. Dissolved H2 can be monitored in solution to ensure true operando conditions without gas limitation. 31P{1H} and selective excitation 1H pulse sequences have been periodically interleaved with 1H FlowNMR measurements to detect Rh-phosphine intermediates during the catalysis. Stopped-flow experiments in combination with diffusion measurements and 2D heteronuclear correlation experiments showed the known tris-phosphine complex [RhH(CO)(PPh3)3] to generate rapidly exchanging isomers of the bis-phosphine complex [Rh(CO)2(PPh3)2] under CO pressure that directly enter the catalytic cycle. A new mono-phosphine acyl complex has been identified as an in-cycle reaction intermediate.

Selective Catalytic Synthesis of 1,2- and 8,9-Cyclic Limonene Carbonates as Versatile Building Blocks for Novel Hydroxyurethanes.

The selective catalytic synthesis of limonene-derived monofunctional cyclic carbonates and their subsequent functionalisation via thiol-ene addition and amine ring-opening is reported. A phosphotungstate polyoxometalate catalyst used for limonene epoxidation in the 1,2-position is shown to also be active in cyclic carbonate synthesis, allowing a two-step, one-pot synthesis without intermittent epoxide isolation. When used in conjunction with a classical halide catalyst, the polyoxometalate increased the rate of carbonation in a synergistic double-activation of both substrates. The cis isomer is shown to be responsible for incomplete conversion and by-product formation in commercial mixtures of 1,2-limomene oxide. Carbonation of 8,9-limonene epoxide furnished the 8,9-limonene carbonate for the first time. Both cyclic carbonates underwent thiol-ene addition reactions to yield linked di-monocarbonates, which can be used in linear non-isocyanate polyurethanes synthesis, as shown by their facile ring-opening with N-hexylamine. Thus, the selective catalytic route to monofunctional limonene carbonates gives straightforward access to monomers for novel bio-based polymers.

Insight into catalyst speciation and hydrogen co-evolution during enantioselective formic acid-driven transfer hydrogenation with bifunctional ruthenium complexes from multi-technique operando reaction monitoring.

Transfer hydrogenation of acetophenone from formic acid/triethylamine mixtures catalysed by the Ikariya-Noyori complex [(mesitylene)RuCl(R,R)-(TsDPEN)] has been investigated using simultaneous high-resolution FlowNMR and FlowUV-Vis spectroscopies coupled with on-line sampling head-space mass spectrometry and chiral high-performance liquid chromatography using an integrated, fully automated recirculating flow setup. In line with previous observations, the combined results show a gradual switch from formic acid dehydrogenation to hydrogen transfer mediated by the same Ru-hydride complex, and point to a Ru-formate species as the major catalyst intermediate. Hydrogen bonding in the formic acid/triethylamine mixture emerges as a sensitive 1H NMR probe for the transfer hydrogenation activity of the system and can be used to locate optimum reaction conditions.

Unlocking the potential of supported liquid phase catalysts with supercritical fluids: low temperature continuous flow catalysis with integrated product separation.

Solution-phase catalysis using molecular transition metal complexes is an extremely powerful tool for chemical synthesis and a key technology for sustainable manufacturing. However, as the reaction complexity and thermal sensitivity of the catalytic system increase, engineering challenges associated with product separation and catalyst recovery can override the value of the product. This persistent downstream issue often renders industrial exploitation of homogeneous catalysis uneconomical despite impressive batch performance of the catalyst. In this regard, continuous-flow systems that allow steady-state homogeneous turnover in a stationary liquid phase while at the same time effecting integrated product separation at mild process temperatures represent a particularly attractive scenario. While continuous-flow processing is a standard procedure for large volume manufacturing, capitalizing on its potential in the realm of the molecular complexity of organic synthesis is still an emerging area that requires innovative solutions. Here we highlight some recent developments which have succeeded in realizing such systems by the combination of near- and supercritical fluids with homogeneous catalysts in supported liquid phases. The cases discussed exemplify how all three levels of continuous-flow homogeneous catalysis (catalyst system, separation strategy, process scheme) must be matched to locate viable process conditions.

Electrochemical activation of Cp* iridium complexes for electrode-driven water-oxidation catalysis.

Organometallic iridium complexes bearing oxidatively stable chelate ligands are precursors for efficient homogeneous water-oxidation catalysts (WOCs), but their activity in oxygen evolution has so far been studied almost exclusively with sacrificial chemical oxidants. In this report, we study the electrochemical activation of Cp*Ir complexes and demonstrate true electrode-driven water oxidation catalyzed by a homogeneous iridium species in solution. Whereas the Cp* precursors exhibit no measurable O2-evolution activity, the molecular species formed after their oxidative activation are highly active homogeneous WOCs, capable of electrode-driven O2 evolution with high Faradaic efficiency. We have ruled out the formation of heterogeneous iridium oxides, either as colloids in solution or as deposits on the surface of the electrode, and found indication that the conversion of the precursor to the active molecular species occurs by a similar process whether carried out by chemical or electrochemical methods. This work makes these WOCs more practical for application in photoelectrochemical dyads for light-driven water splitting.

Modes of activation of organometallic iridium complexes for catalytic water and C-H oxidation.

Sodium periodate (NaIO4) is added to Cp*Ir(III) (Cp* = C5Me5(-)) or (cod)Ir(I) (cod = cyclooctadiene) complexes, which are water and C-H oxidation catalyst precursors, and the resulting aqueous reaction is investigated from milliseconds to seconds using desorption electrospray ionization, electrosonic spray ionization, and cryogenic ion vibrational predissociation spectroscopy. Extensive oxidation of the Cp* ligand is observed, likely beginning with electrophilic C-H hydroxylation of a Cp* methyl group followed by nonselective pathways of further oxidative degradation. Evidence is presented that the supporting chelate ligand in Cp*Ir(chelate) precursors influences the course of oxidation and is neither eliminated from the coordination sphere nor oxidatively transformed. Isomeric products of initial Cp* oxidation are identified and structurally characterized by vibrational spectroscopy in conjunction with density functional theory (DFT) modeling. Less extensive but more rapid oxidation of the cod ligand is also observed in the (cod)Ir(I) complexes. The observations are consistent with the proposed role of Cp* and cod as sacrificial placeholder ligands that are oxidatively removed from the precursor complexes under catalytic conditions.

Twinned versus linked organometallics - bimetallic "half-baguette" pentalenide complexes of Rh(I).

The application of Mg[Ph4Pn] and Li·K[Ph4Pn] in transmetalation reactions to a range of Rh(I) precursors led to the formation of "half-baguette" anti-[RhI(L)n]2[µ:η5:η5Ph4Pn] (L = 1,5-cyclooctadiene, norbornadiene, ethylene; n = 1, 2) and syn-[RhI(CO)2]2[µ:η5:η5Ph4Pn] complexes as well as the related iridium complex anti-[IrI(COD)]2[µ:η5:η5Ph4Pn]. With CO exclusive syn metalation was obtained even when using mono-nuclear Rh(I) precursors, indicating an electronic preference for syn metalation. DFT analysis showed this to be the result of π overlap between the adjacent M(CO)2 units which overcompensates for dz2 repulsion of the metals, an effect which can be overridden by steric clash of the auxiliary ligands to yield anti-configuration as seen in the larger olefin complexes. syn-[RhI(CO)2]2[µ:η5:η5Ph4Pn] is a rare example of a twinned organometallic where the two metals are held flexibly in close proximity, but the two d8 Rh(I) centres did not show signs of M-M bonding interactions or exhibit Lewis basic behaviour as in some related mono-nuclear Cp complexes due to the acceptor properties of the ligands. The ligand substitution chemistry of syn-[RhI(CO)2]2[µ:η5:η5Ph4Pn] was investigated with a series of electronically and sterically diverse donor ligands (P(OPh)3, P(OMe)3, PPh3, PMe3, dppe) yielding new mono- and bis-substituted complexes, with E-syn-[RhI(CO)(P{OR})3]2[µ:η5:η5Ph4Pn] (R = Me, Ph) characterised by XRD.

Water co-catalysis in aerobic olefin epoxidation mediated by ruthenium oxo complexes.

We report the development of a versatile Ru-porphyrin catalyst system which performs the aerobic epoxidation of aromatic and aliphatic (internal) alkenes under mild conditions, with product yields of up to 95% and turnover numbers (TON) up to 300. Water is shown to play a crucial role in the reaction, significantly increasing catalyst efficiency and substrate scope. Detailed mechanistic investigations employing both computational studies and a range of experimental techniques revealed that water activates the RuVI di-oxo complex for alkene epoxidation via hydrogen bonding, stabilises the RuIV mono-oxo intermediate, and is involved in the regeneration of the RuVI di-oxo complex leading to oxygen atom exchange. Distinct kinetics are obtained in the presence of water, and side reactions involved in catalyst deactivation have been identified.

Precursor transformation during molecular oxidation catalysis with organometallic iridium complexes.

We present evidence for Cp* being a sacrificial placeholder ligand in the [Cp*Ir(III)(chelate)X] series of homogeneous oxidation catalysts. UV-vis and (1)H NMR profiles as well as MALDI-MS data show a rapid and irreversible loss of the Cp* ligand under reaction conditions, which likely proceeds through an intramolecular inner-sphere oxidation pathway reminiscent of the reductive in situ elimination of diolefin placeholder ligands in hydrogenation catalysis by [(diene)M(I)(L,L')](+) (M = Rh and Ir) precursors. When oxidatively stable chelate ligands are bound to the iridium in addition to the Cp*, the oxidized precursors yield homogeneous solutions with a characteristic blue color that remain active in both water- and CH-oxidation catalysis without further induction period. Electrophoresis suggests the presence of well-defined Ir-cations, and TEM-EDX, XPS, (17)O NMR, and resonance-Raman spectroscopy data are most consistent with the molecular identity of the blue species to be a bis-µ-oxo di-iridium(IV) coordination compound with two waters and one chelate ligand bound to each metal. DFT calculations give insight into the electronic structure of this catalyst resting state, and time-dependent simulations agree with the assignments of the experimental spectroscopic data. [(cod)Ir(I)(chelate)] precursors bearing the same chelate ligands are shown to be equally effective precatalysts for both water- and CH-oxidations using NaIO4 as chemical oxidant.

A fully integrated continuous-flow system for asymmetric catalysis: enantioselective hydrogenation with supported ionic liquid phase catalysts using supercritical CO(2) as the mobile phase.

A continuous-flow process based on a chiral transition-metal complex in a supported ionic liquid phase (SILP) with supercritical carbon dioxide (scCO(2)) as the mobile phase is presented for asymmetric catalytic transformations of low-volatility organic substrates at mild reaction temperatures. Enantioselectivity of >99% ee and quantitative conversion were achieved in the hydrogenation of dimethylitaconate for up to 30 h, reaching turnover numbers beyond 100000 for the chiral QUINAPHOS-rhodium complex. By using an automated high-pressure continuous-flow setup, the product was isolated in analytically pure form without the use of any organic co-solvent and with no detectable catalyst leaching. Phase-behaviour studies and high-pressure NMR spectroscopy assisted the localisation of optimum process parameters by quantification of substrate partitioning between the IL and scCO(2). Fundamental insight into the molecular interactions of the metal complex, ionic liquid and the surface of the support in working SILP catalyst materials was gained by means of systematic variations, spectroscopic studies and labelling experiments. In concert, the obtained results provided a rationale for avoiding progressive long-term deactivation. The optimised system reached stable selectivities and productivities that correspond to 0.7 kgL(-1)h(-1) space-time yield and at least 100 kg product per gram of rhodium, thus making such processes attractive for larger-scale application.

Particle formation during oxidation catalysis with Cp* iridium complexes.

Real-time monitoring of light scattering and UV-vis profiles of four different Cp*Ir(III) precursors under various conditions give insight into nanoparticle formation during oxidation catalysis with NaIO(4) as primary oxidant. Complexes bearing chelate ligands such as 2,2'-bipyridine, 2-phenylpyridine, or 2-(2'-pyridyl)-2-propanolate were found to be highly resistant toward particle formation, and oxidation catalysis with these compounds is thus believed to be molecular in nature under our conditions. Even with the less stable hydroxo/aqua complex [Cp*(2)Ir(2)(µ-OH)(3)]OH, nanoparticle formation strongly depended on the exact conditions and elapsed time. Test experiments on the isolated particles and comparison of UV-vis data with light scattering profiles revealed that the formation of a deep purple-blue color (~580 nm) is not indicative of particle formation during oxidation catalysis with molecular iridium precursors as suggested previously.

Continuous-flow hydrogenation of carbon dioxide to pure formic acid using an integrated scCO2 process with immobilized catalyst and base.

Dual role for CO(2): Pure formic acid can be obtained continuously by hydrogenation of CO(2) in a single processing unit. An immobilized ruthenium organometallic catalyst and a nonvolatile base in an ionic liquid (IL) are combined with supercritical CO(2) as both reactant and extractive phase.

Sustainable Synthesis of Dimethyl- and Diethyl Carbonate from CO2 in Batch and Continuous Flow-Lessons from Thermodynamics and the Importance of Catalyst Stability.

Equilibrium conversions for the direct condensation of MeOH and EtOH with CO2 to give dimethyl- and diethyl carbonate, respectively, have been calculated over a range of experimentally relevant conditions. The validity of these calculations has been verified in both batch and continuous flow experiments over a heterogeneous CeO2 catalyst. Operating under optimized conditions of 140 °C and 200 bar CO2, record productivities of 235 mmol/L·h DMC and 241 mmol/L·h DEC have been achieved using neat alcohol dissolved in a continuous flow of supercritical CO2. Using our thermodynamic model, we show that to achieve maximum product yield, both dialkyl carbonates and water should be continuously removed from the reactor instead of the conventionally used strategy of removing water alone, which is much less efficient. Catalyst stability rather than activity emerges as the prime limiting factor and should thus become the focus of future catalyst development.