The Effect of Conformational Freedom vs Restriction on the Rate in Asymmetric Hydrogenation: Iridium-Catalyzed Regio- and Enantioselective Monohydrogenation of Dienones.

Transition metal-catalyzed asymmetric hydrogenation constitutes an efficient strategy for the preparation of chiral molecules. When dienes are subjected to hydrogenation, control over regioselectivity still presents a large challenge and the fully saturated alkane is often yielded. A few successful monohydrogenations of dienes have been reported, but hitherto these are only efficient for dienes comprised of two distinctly different olefins. Herein, the reactivity of a conjugated carbonyl compound as a function of their conformational freedom is studied, based on a combined experimental and theoretical approach. It was found that alkenes in the (s)-cis conformation experience a large rate acceleration while (s)-trans restrained alkenes undergo hydrogenation slowly. Ultimately, this reactivity aspect was exploited in a novel method for the monohydrogenation of dienes based on conformational restriction ((s)-cis vs (s)-trans). This mode of discrimination conceptually differs from existing monohydrogenations and dienones constructed of two olefins similar in nature could efficiently be hydrogenated to the chiral alkene (up to 99 % ee). The extent of regioselection is even powerful enough to overcome the conventional reactivity order of substituted olefins (di>tri>tetra). This high yielding and atom-economical protocol provides an interesting opportunity to instal a stereogenic center on a carbocycle, while leaving a synthetically useful alkene untouched.

Removing the Barrier in O-O Bond Formation Via the Combination of Intramolecular Radical Coupling and the Oxide Relay Mechanism.

The Ru(tda) catalyst has been a major milestone in the development of molecular water oxidation catalysts due to its outstanding performance at neutral pH. The role of the noncoordinating carboxylate group is to act as a nucleophile, donating an oxygen atom to the oxo group, thereby acting as an oxide relay (OR) mechanism for O-O bond formation. A substitution of the carboxylates for phosphonate groups has been proposed, resulting in the Ru(tPaO) catalyst, which has shown even more efficient performance in experimental characterization. In this study, we explore the feasibility of the OR mechanism in the newly reported Ru(tPaO) molecular catalyst. We investigated the catalytic cycle using density functional theory and identified a variation of the OR mechanism that involves radical oxygen atoms in O-O bond formation. We have also determined that the subsequent hydroxide nucleophilic attack is the sole rate-limiting step in the catalytic cycle. All activation free energies are very low, with a free-energy barrier of 2.1 kcal/mol for O-O bond formation and 4.2 kcal/mol for OH- nucleophilic attack.

Bioinspired Active Site with a Coordination-Adaptive Organosulfonate Ligand for Catalytic Water Oxidation at Neutral pH.

Many enzymes use adaptive frameworks to preorganize substrates, accommodate various structural and electronic demands of intermediates, and accelerate related catalysis. Inspired by biological systems, a Ru-based molecular water oxidation catalyst containing a configurationally labile ligand [2,2':6',2″-terpyridine]-6,6″-disulfonate was designed to mimic enzymatic framework, in which the sulfonate coordination is highly flexible and functions as both an electron donor to stabilize high-valent Ru and a proton acceptor to accelerate water dissociation, thus boosting the catalytic water oxidation performance thermodynamically and kinetically. The combination of single-crystal X-ray analysis, various temperature NMR, electrochemical techniques, and DFT calculations was utilized to investigate the fundamental role of the self-adaptive ligand, demonstrating that the on-demand configurational changes give rise to fast catalytic kinetics with a turnover frequency (TOF) over 2000 s-1, which is compared to oxygen-evolving complex (OEC) in natural photosynthesis.

Development and mechanistic investigation of the dehydrogenation of alcohols with an iron(III) salen catalyst.

The iron(III) salen complex (R,R)-N,N'-bis(salicylidene)-1,2-cyclohexanediamineiron(III) chloride has been developed as a catalyst for the acceptorless dehydrogenation of alcohols. The complex catalyzes the direct synthesis of imines in good yields from different primary alcohols and amines with the liberation of hydrogen gas. The mechanism has been investigated experimentally with labelled substrates and theoretically with density functional theory calculations. In contrast to the corresponding manganese(III) salen-catalyzed dehydrogenation, it has not been possible to identify a homogeneous catalytic pathway with the iron complex. Instead, poisoning experiments with trimethylphosphine and mercury indicated that the catalytically active species are heterogeneous small iron particles.

Microscopic Insights into Cation-Coupled Electron Hopping Transport in a Metal-Organic Framework.

Electron transport through metal-organic frameworks by a hopping mechanism between discrete redox active sites is coupled to diffusion-migration of charge-balancing counter cations. Experimentally determined apparent diffusion coefficients, Deapp, that characterize this form of charge transport thus contain contributions from both processes. While this is well established for MOFs, microscopic descriptions of this process are largely lacking. Herein, we systematically lay out different scenarios for cation-coupled electron transfer processes that are at the heart of charge diffusion through MOFs. Through systematic variations of solvents and electrolyte cations, it is shown that the Deapp for charge migration through a PIZOF-type MOF, Zr(dcphOH-NDI) that is composed of redox-active naphthalenediimide (NDI) linkers, spans over 2 orders of magnitude. More importantly, however, the microscopic mechanisms for cation-coupled electron propagation are contingent on differing factors depending on the size of the cation and its propensity to engage in ion pairs with reduced linkers, either non-specifically or in defined structural arrangements. Based on computations and in agreement with experimental results, we show that ion pairing generally has an adverse effect on cation transport, thereby slowing down charge transport. In Zr(dcphOH-NDI), however, specific cation-linker interactions can open pathways for concerted cation-coupled electron transfer processes that can outcompete limitations from reduced cation flux.

Promoting Proton Transfer and Stabilizing Intermediates in Catalytic Water Oxidation via Hydrophobic Outer Sphere Interactions.

The outer coordination sphere of metalloenzyme often plays an important role in its high catalytic activity, however, this principle is rarely considered in the design of man-made molecular catalysts. Herein, four Ru-bda (bda=2,2'-bipyridine-6,6'-dicarboxylate) based molecular water oxidation catalysts with well-defined outer spheres are designed and synthesized. Experimental and theoretical studies showed that the hydrophobic environment around the Ru center could lead to thermodynamic stabilization of the high-valent intermediates and kinetic acceleration of the proton transfer process during catalytic water oxidation. By this outer sphere stabilization, a 6-fold rate increase for water oxidation catalysis has been achieved.

Promoting Selective Generation of Formic Acid from CO2 Using Mn(bpy)(CO)3Br as Electrocatalyst and Triethylamine/Isopropanol as Additives.

Urgent solutions are needed to efficiently convert the greenhouse gas CO2 into higher-value products. In this work, fac-Mn(bpy)(CO)3Br (bpy = 2,2'-bipyridine) is employed as electrocatalyst in reductive CO2 conversion. It is shown that product selectivity can be shifted from CO toward HCOOH using appropriate additives, i.e., Et3N along with iPrOH. A crucial aspect of the strategy is to outrun the dimer-generating parent-child reaction involving fac-Mn(bpy)(CO)3Br and [Mn(bpy)(CO)3]- and instead produce the Mn hydride intermediate. Preferentially, this is done at the first reduction wave to enable formation of HCOOH at an overpotential as low as 260 mV and with faradaic efficiency of 59 ± 1%. The latter may be increased to 71 ± 3% at an overpotential of 560 mV, using 2 M concentrations of both Et3N and iPrOH. The nature of the amine additive is crucial for product selectivity, as the faradaic efficiency for HCOOH formation decreases to 13 ± 4% if Et3N is replaced with Et2NH. The origin of this difference lies in the ability of Et3N/iPrOH to establish an equilibrium solution of isopropyl carbonate and CO2, while with Et2NH/iPrOH, formation of the diethylcarbamic acid is favored. According to density-functional theory calculations, CO2 in the former case can take part favorably in the catalytic cycle, while this is less opportune in the latter case because of the CO2-to-carbamic acid conversion. This work presents a straightforward procedure for electrochemical reduction of CO2 to HCOOH by combining an easily synthesized manganese catalyst with commercially available additives.

Combined Theoretical and Experimental Studies Unravel Multiple Pathways to Convergent Asymmetric Hydrogenation of Enamides.

We present a highly efficient convergent asymmetric hydrogenation of E/Z mixtures of enamides catalyzed by N,P-iridium complexes supported by mechanistic studies. It was found that reduction of the olefinic isomers (E and Z geometries) produces chiral amides with the same absolute configuration (enantioconvergent hydrogenation). This allowed the hydrogenation of a wide range of E/Z mixtures of trisubstituted enamides with excellent enantioselectivity (up to 99% ee). A detailed mechanistic study using deuterium labeling and kinetic experiments revealed two different pathways for the observed enantioconvergence. For α-aryl enamides, fast isomerization of the double bond takes place, and the overall process results in kinetic resolution of the two isomers. For α-alkyl enamides, no double bond isomerization is detected, and competition experiments suggested that substrate chelation is responsible for the enantioconvergent stereochemical outcome. DFT calculations were performed to predict the correct absolute configuration of the products and strengthen the proposed mechanism of the iridium-catalyzed isomerization pathway.

Electrostatic Interactions Accelerating Water Oxidation Catalysis via Intercatalyst O-O Coupling.

Intercatalyst coupling has been widely applied in the functional mimics for binuclear synergy in natural metal enzymes. Herein, we introduce two facile and effective design strategies, which facilitate the coupling of two catalytic units via electrostatic interactions. The first system is based on a catalyst molecule functionalized with both a positively charged and a negatively charged group in the structure being able to pair with each other in an antiparallel manner arranged by electrostatic interactions. The other system consists of a mixture of two different of catalysts modified with either positively or negatively charged groups to generate intermolecular electrostatic interactions. Applying these designs to Ru(bda) (H2bda = 2,2'-bipyridine-6,6'-dicarboxylic acid) water-oxidation catalysts improved the catalytic performance by more than an order of magnitude. The intermolecular electrostatic interactions in these two systems were fully identified by 1H NMR, TEM, SAXS, and electrical conductivity experiments. Molecular dynamics simulations further verified that electrostatic interactions contribute to the formation of prereactive dimers, which were found to play a key role in dramatically improving the catalytic performance. The successful strategies demonstrated here can be used in designing other intercatalyst coupling systems for activation and formation of small molecules and organic synthesis.

Pivotal Electron Delivery Effect of the Cobalt Catalyst in Photocarboxylation of Alkynes: A DFT Calculation.

Photocarboxylation of alkyne with carbon dioxide represents a highly attractive strategy to prepare functionalized alkenes with high efficiency and atomic economy. However, the reaction mechanism, especially the sequence of elementary steps (leading to different reaction pathways), reaction modes of the H-transfer step and carboxylation step, spin and charge states of the cobalt catalyst, etc., is still an open question. Herein, density functional theory calculations are carried out to probe the mechanism of the Ir/Co-catalyzed photocarboxylation of alkynes. The overall catalytic cycle mainly consists of four steps: reductive-quenching of the Ir catalyst, hydrogen transfer (rate-determining step), outer sphere carboxylation, and the final catalyst regeneration step. Importantly, the cobalt catalyst can facilitate the H-transfer by an uncommon hydride coupled electron transfer (HCET) process. The pivotal electron delivery effect of the Co center enables a facile H-transfer to the α-C(alkyne) of the aryl group, resulting in the high regioselectivity for ß-carboxylation.

Site- and Enantioselective Iridium-Catalyzed Desymmetric Mono-Hydrogenation of 1,4-Dienes.

The control of site selectivity in asymmetric mono-hydrogenation of dienes or polyenes remains largely underdeveloped. Herein, we present a highly efficient desymmetrization of 1,4-dienes via iridium-catalyzed site- and enantioselective hydrogenation. This methodology demonstrates the first iridium-catalyzed hydrogenative desymmetriation of meso dienes and provides a concise approach to the installation of two vicinal stereogenic centers adjacent to an alkene. High isolated yields (up to 96 %) and excellent diastereo- and enantioselectivities (up to 99:1 d.r. and 99 % ee) were obtained for a series of divinyl carbinol and divinyl carbinamide substrates. DFT calculations reveal that an interaction between the hydroxy oxygen and the reacting hydride is responsible for the stereoselectivity of the desymmetrization of the divinyl carbinol. Based on the calculated energy profiles, a model that simulates product distribution over time was applied to show an intuitive kinetics of this process. The usefulness of the methodology was demonstrated by the synthesis of the key intermediates of natural products zaragozic acid A and (+)-invictolide.

The Carboxylate Ligand as an Oxide Relay in Catalytic Water Oxidation.

Carboxylate groups have diverse functionalities in ligands of transition metal catalysts. Here we present a conceptually different function of the carboxylates: the oxide relay. It functions by providing an intramolecular nucleophilic oxygen close to the oxo group to facilitate O-O bond formation and at a later stage a remote electrophilic center to facilitate OH- nucleophilic attack. Empirical valence bond-molecular dynamics (EVB-MD) models were generated for key bond forming steps, diffusion coefficients and binding free energies from potential of mean force estimations were calculated from molecular dynamics (MD) simulations, activation free energies of chemical steps were calculated using density functional theory (DFT). The catalyst studied is the extremely active Ru(tda)(py)2 water oxidation catalyst. The combination of simulation methods allowed for estimation of the turnover frequencies, which were within 1 order of magnitude from the experimental results at different pH values. From the calculated reaction rates we find that at low pH the OH- anion nucleophilic attack is the rate-limiting step, which changes at high pH to the O-O bond formation step. Both steps are extremely rapid, and key to the efficiency is the oxide relay functionality of a pendant carboxylate group. We cannot exclude all alternative mechanisms and suggest isotope experiments using 18O-labeled water to support or invalidate the oxide relay mechanism. The functionality was discovered for a ruthenium catalyst, but since there is nothing in the mechanism restricting it to this metal, the oxide relay functionality could open new ways to design the next-generation water oxidation catalysts with improved activity.

Paired Electrocatalytic Oxygenation and Hydrogenation of Organic Substrates with Water as the Oxygen and Hydrogen Source.

The use of water as an oxygen and hydrogen source for the paired oxygenation and hydrogenation of organic substrates to produce valuable chemicals is of utmost importance as a means of establishing green chemical syntheses. Inspired by the active Ni3+ intermediates involved in electrocatalytic water oxidation by nickel-based materials, we prepared NiBx as a catalyst and used water as the oxygen source for the oxygenation of various organic compounds. NiBx was further employed as both an anode and a cathode in a paired electrosynthesis cell for the respective oxygenation and hydrogenation of organic compounds, with water as both the oxygen and hydrogen source. Conversion efficiency and selectivity of ≥99 % were observed during the oxygenation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid and the simultaneous hydrogenation of p-nitrophenol to p-aminophenol. This paired electrosynthesis cell has also been coupled to a solar cell as a stand-alone reactor in response to sunlight.

Dynamics and Reactions of Molecular Ru Catalysts at Carbon Nanotube-Water Interfaces.

Immobilization of molecular catalysts to electrode surfaces can improve the recyclability and electron transfer rates. The drawback is that most experimental techniques and theoretical methods are not applicable. Here we present results from a study of a ruthenium water oxidation catalyst [RuVO(bda)L2] in explicit water at a carbon nanotube water interface, forming the key O-O bond between two 128 atom catalysts, all fully dynamically. Our methodology is based on a recently developed empirical valence bond (EVB) model. We follow the key steps of the reaction including diffusion of the catalysts at the interface, formation of the prereactive dimer, and the bond formation between the two catalysts. On the basis of the calculated parameters, we compute the turnover frequency (TOF) at the experimental loading, in excellent agreement with the experiments. The key O-O bond formation was significantly retarded at the surface, and limiting components were identified that could be improved by catalyst modification.

Mechanistic Studies on NaHCO3 Hydrogenation and HCOOH Dehydrogenation Reactions Catalysed by a FeII Linear Tetraphosphine Complex.

We present a theoretical extension of the previously published bicarbonate hydrogenation to formate and formic acid dehydrogenation catalysed by FeII complexes bearing the linear tetraphosphine ligand tetraphos-1. The hydrogenation reaction was found to proceed at the singlet surface with two competing pathways: A) H2 association to the Fe-H species followed by deprotonation to give a Fe(H)2 intermediate, which then reacts with CO2 to give formate. B) CO2 insertion into the Fe-H bond, followed by H2 association and subsequent deprotonation. B was found to be slightly preferred with an activation energy of 22.8 kcal mol-1 , compared to 25.3 for A. Further we have reassigned the Fe-H complex, as a Fe(H)(H2 ), which undergoes extremely rapid hydrogen exchange.

Csp3 -H Activation without Chelation Assistance in an Iridium Pincer Complex Forming Cyclometallated Products.

Cyclometallation of 8-methylquinoline and 2-(dimethylamino)-pyridine in an iridium-based pincer complex is described. The C-H activation of 2-(dimethylamino)pyridine is not chelation assisted, which has not been described before for Csp3 -H bonds in cyclometallation reactions. The mechanism of the cyclometallation of 2-(dimethylamino)pyridine was studied by DFT calculations and kinetic measurements.

Capturing the Role of Explicit Solvent in the Dimerization of RuV (bda) Water Oxidation Catalysts.

A ground-breaking empirical valence bond study for a soluble transition-metal complex is presented. The full reaction of catalyst monomers approaching and reacting in the RuV oxidation state were studied. Analysis of the solvation shell in the reactant and along the reaction coordinate revealed that the oxo itself is hydrophobic, which adds a significant driving force to form the dimer. The effect of the solvent on the reaction between the prereactive dimer and the product was small. The solvent seems to lower the barrier for the isoquinoline (isoq) complex while it is increased for pyridines. By comparing the reaction in the gas phase and solution, the proposed π-stacking interaction of the isoq ligands is found to be entirely driven by the water medium.

Base-Catalyzed Stereospecific Isomerization of Electron-Deficient Allylic Alcohols and Ethers through Ion-Pairing.

A mild base-catalyzed strategy for the isomerization of allylic alcohols and allylic ethers has been developed. Experimental and computational investigations indicate that transition metal catalysts are not required when basic additives are present. As in the case of using transition metals under basic conditions, the isomerization catalyzed solely by base also follows a stereospecific pathway. The reaction is initiated by a rate-limiting deprotonation. Formation of an intimate ion pair between an allylic anion and the conjugate acid of the base results in efficient transfer of chirality. Through this mechanism, stereochemical information contained in the allylic alcohols is transferred to the ketone products. The stereospecific isomerization is also applicable for the first time to allylic ethers, yielding synthetically valuable enantioenriched (up to 97% ee) enol ethers.

Solvent-Dependent Structure of Iridium Dihydride Complexes: Different Geometries at Low and High Dielectricity of the Medium.

The hydride iridium pincer complex [(PCyP)IrH2] (PCyP=cis-1,3-bis[(di-tert-butylphosphino)methyl]cyclohexane, 1) reveals remarkably solvent-dependent hydride chemical shifts, isotope chemical shifts, JHD and T1(min), with rHH increasing upon moving to more polar medium. The only known example of such behaviour (complex [(POCOP)IrH2], POCOP=2,6-(tBu2PO)2C6H3) was explained by the coordination of a polar solvent molecule to the iridium (J. Am. Chem. Soc. 2006, 128, 17114). Based on the existence of an agostic bond between α-C-H and iridium in 1 in all solvents, we argue that the coordination of solvent can be rejected. DFT calculations revealed that the structures of 1 and [(POCOP)IrH2] depend on the dielectric permittivity of the medium and these compounds adopt trigonal-bipyramidal geometries in non-polar media and square-pyramidal geometries in polar media.

Light-Driven Proton Reduction in Aqueous Medium Catalyzed by a Family of Cobalt Complexes with Tetradentate Polypyridine-Type Ligands.

A series of tetradentate 2,2':6',2″:6″,2‴-quaterpyridine-type ligands related to ppq (ppq = 8-(1″,10″-phenanthrol-2″-yl)-2-(pyrid-2'-yl)quinoline) have been synthesized. One ligand replaces the 1,10-phenanthroline (phen) moiety of ppq with 2,2'-bipyridine and the other two ligands have a 3,3'-polymethylene subunit bridging the quinoline and pyridine. The structural result is that both the planarity and flexibility of the ligand are modified. Co(II) complexes are prepared and characterized by ultraviolet-visible light (UV-vis) and mass spectroscopy, cyclic voltammetry, and X-ray analysis. The light-driven H2-evolving activity of these Co complexes was evaluated under homogeneous aqueous conditions using [Ru(bpy)3](2+) as the photosensitizer, ascorbic acid as a sacrificial electron donor, and a blue light-emitting diode (LED) as the light source. At pH 4.5, all three complexes plus [Co(ppq)Cl2] showed the fastest rate, with the dimethylene-bridged system giving the highest turnover frequency (2125 h(-1)). Cyclic voltammograms showed a significant catalytic current for H2 production in both aqueous buffer and H2O/DMF medium. Combined experimental and theoretical study suggest a formal Co(II)-hydride species as a key intermediate that triggers H2 generation. Spin density analysis shows involvement of the tetradentate ligand in the redox sequence from the initial Co(II) state to the Co(II)-hydride intermediate. How the ligand scaffold influences the catalytic activity and stability of catalysts is discussed, in terms of the rigidity and differences in conjugation for this series of ligands.