Direct Analysis of Complex Reaction Mixtures: Formose Reaction.

Complex reaction mixtures, like those postulated on early Earth, present an analytical challenge because of the number of components, their similarity, and vastly different concentrations. Interpreting the reaction networks is typically based on simplified or partial data, limiting our insight. We present a new approach based on online monitoring of reaction mixtures formed by the formose reaction by ion-mobility-separation mass-spectrometry. Monitoring the reaction mixtures led to large data sets that we analyzed by non-negative matrix factorization, thereby identifying ion-signal groups capturing the time evolution of the network. The groups comprised ≈300 major ion signals corresponding to sugar-calcium complexes formed during the formose reaction. Multivariate analysis of the kinetic profiles of these complexes provided an overview of the interconnected kinetic processes in the solution, highlighting different pathways for sugar growth and the effects of different initiators on the initial kinetics. Reconstructing the network's topology further, we revealed so far unnoticed fast retro-aldol reaction of ketoses, which significantly affects the initial reaction dynamics. We also detected the onset of sugar-backbone branching for C6  sugars and cyclization reactions starting for C5  sugars. This top-down analytical approach opens a new way to analyze complex dynamic mixtures online with unprecedented coverage and time resolution.

Properties of Metal Hydrides of the Iron Triad.

Metal hydride complexes are essential intermediates in hydrogenation reactions. The hydride-donor ability determines the scope of use of these complexes. We present a new, simple mass-spectrometry method to study the hydride-donor ability of metal hydrides using a series of 18 iron, cobalt, and nickel complexes with N- and P-based ligands (L). The mixing of [(L)MII(OTf)2] with NaBH4 forms [(L)MII(BH4)]+ (M = Fe, Co, Ni) that can be detected by electrospray ionization mass spectrometry. Energy-resolved collision-induced dissociations of [(L)MII(BH4)]+ provide threshold energies (ΔECID) for the formations of [(L)MII(H)]+ that correlate well with the hydride donor ability of the metal hydride complexes. We studied the vibrational and electronic spectra of the generated metal hydrides, assigned their structure and spin state, and demonstrated a good correlation between ΔECID and the M-H stretching vibration frequencies. The ΔECID also correlates with reaction rates for hydride transfer reactivity in the gas phase and known reactivity trends in the solution phase.

Kinetic enantio-recognition of chiral viologen guests by planar-chiral porphyrin cages.

The kinetic enantio-recognition of chiral viologen guests by planar-chiral porphyrin cage compounds, measured in terms of ΔΔG‡on, is determined by the planar-chirality of the host and influenced by the size, as measured by ion mobility-mass spectrometry, but not the chirality of its substituents.

Generation, Spectroscopic Characterization, and Computational Analysis of a Six-Coordinate Cobalt(III)-Imidyl Complex with an Unusual S = 3/2 Ground State that Promotes N-Group and Hydrogen Atom-Transfer Reactions with Exogenous Substrates.

We report the synthesis and characterization of a mononuclear nonheme cobalt(III)-imidyl complex, [Co(NTs)(TQA)(OTf)]+ (1), with an S = 3/2 spin state that is capable of facilitating exogenous substrate modifications. Complex 1 was generated from the reaction of CoII(TQA)(OTf)2 with PhINTs at -20 °C. A flow setup with ESI-MS detection was used to explore the kinetics of the formation, stability, and degradation pathway of 1 in solution by treating the Co(II) precursor with PhINTs. Co K-edge XAS data revealed a distinct shift in the Co K-edge compared to the Co(II) precursor, in agreement with the formation of a Co(III) intermediate. The unusual S = 3/2 spin state was proposed based on EPR, DFT, and CASSCF calculations and Co Kß XES results. Co K-edge XAS and IR photodissociation (IRPD) spectroscopies demonstrate that 1 is a six-coordinate species, and IRPD and resonance Raman spectroscopies are consistent with 1 being exclusively the isomer with the NT ligand occupying the vacant site trans to the TQA aliphatic amine nitrogen atom. Electronic structure calculations (broken symmetry DFT and CASSCF/NEVPT2) demonstrate an S = 3/2 oxidation state resulting from the strong antiferromagnetic coupling of an •NTs spin to the high-spin S = 2 Co(III) center. Reactivity studies of 1 with PPh3 derivatives revealed its electrophilic characteristic in the nitrene-transfer reaction. While the activation of C-H bonds by 1 was proved to be kinetically challenging, 1 could oxidize weak O-H and N-H bonds. Complex 1 is, therefore, a rare example of a Co(III)-imidyl complex capable of exogenous substrate transformations.

Hydrogen Bonding Effect on the Oxygen Binding and Activation in Cobalt(III)-Peroxo Complexes.

Cobalt(III)peroxo complexes serve as model metal complexes mediating oxygen activation. We report a systematic study of the effect of hydrogen bonding on the O2 binding energy and the O-O bond activation within the cobalt(III)peroxo complexes. To this end, we prepared a series of tris(pyridin-2-ylmethyl)amine-based cobalt(III)peroxo complexes having either none, one, two, or three amino groups in the secondary coordination sphere. The hydrogen bonding between the amino group(s) and the peroxo ligand was investigated within the isolated complexes in the gas phase using helium tagging infrared photodissociation spectroscopy, energy-resolved collision-induced dissociation experiments, and density functional theory. The results show that the hydrogen bonding stabilizes the cobalt(III)peroxo core, but the effect is only 10-20 kJ mol-1. Introducing the first amino group to the secondary coordination sphere has the largest stabilization effect; more amino groups do not change the results significantly. The amino group can transfer a hydrogen atom to the peroxo ligands, which results in the O-O bond cleavage. This process is thermodynamically favored over the O2 elimination but entropically disfavored.

Aliphatic and Aromatic C-H Bond Oxidation by High-Valent Manganese(IV)-Hydroxo Species.

The strong C-H bond activation of hydrocarbons is a difficult reaction in environmental and biological chemistry. Herein, a high-valent manganese(IV)-hydroxo complex, [MnIV(CHDAP-O)(OH)]2+ (2), was synthesized and characterized by various physicochemical measurements, such as ultraviolet-visible (UV-vis), electrospray ionization-mass spectrometry (ESI-MS), electron paramagnetic resonance (EPR), and helium-tagging infrared photodissociation (IRPD) methods. The one-electron reduction potential (Ered) of 2 was determined to be 0.93 V vs SCE by redox titration. 2 is formed via a transient green species assigned to a manganese(IV)-bis(hydroxo) complex, [MnIV(CHDAP)(OH)2]2+ (2'), which performs intramolecular aliphatic C-H bond activation. The kinetic isotope effect (KIE) value of 4.8 in the intramolecular oxidation was observed, which indicates that the C-H bond activation occurs via rate-determining hydrogen atom abstraction. Further, complex 2 can activate the C-H bonds of aromatic compounds, anthracene and its derivatives, under mild conditions. The KIE value of 1.0 was obtained in the oxidation of anthracene. The rate constant (ket) of electron transfer (ET) from N,N'-dimethylaniline derivatives to 2 is fitted by Marcus theory of electron transfer to afford the reorganization energy of ET (λ = 1.59 eV). The driving force dependence of log ket for oxidation of anthracene derivatives by 2 is well evaluated by Marcus theory of electron transfer. Detailed kinetic studies, including the KIE value and Marcus theory of outer-sphere electron transfer, imply that the mechanism of aromatic C-H bond hydroxylation by 2 proceeds via the rate-determining electron-transfer pathway.

Mechanistic Studies on the Epoxidation of Alkenes by Macrocyclic Manganese Porphyrin Catalysts.

Macrocyclic metal porphyrin complexes can act as shape-selective catalysts mimicking the action of enzymes. To achieve enzyme-like reactivity, a mechanistic understanding of the reaction at the molecular level is needed. We report a mechanistic study of alkene epoxidation by the oxidant iodosylbenzene, mediated by an achiral and a chiral manganese(V)oxo porphyrin cage complex. Both complexes convert a great variety of alkenes into epoxides in yields varying between 20-88 %. We monitored the process of the formation of the manganese(V)oxo complexes by oxygen transfer from iodosylbenzene to manganese(III) complexes and their reactivity by ion mobility mass spectrometry. The results show that in the case of the achiral cage complex the initial iodosylbenzene adduct is formed on the inside of the cage and in the case of the chiral one on the outside of the cage. Its decomposition leads to a manganese complex with the oxo ligand on either the inside or outside of the cage. These experimental results are confirmed by DFT calculations. The oxo ligand on the outside of the cage reacts faster with a substrate molecule than the oxo ligand on the inside. The results indicate how the catalytic activity of the macrocyclic porphyrin complex can be tuned and explain why the chiral porphyrin complex does not catalyze the enantioselective epoxidation of alkenes.

Unmasking the Iron-Oxo Bond of the [(Ligand)Fe-OIAr]2+/+ Complexes.

ArIO (ArI = 2-(tBuSO2)C6H4I) is an oxidant used to oxidize FeII species to their FeIV-oxo state, enabling hydrogen-atom transfer (HAT) and oxygen-atom transfer (OAT) reactions at low energy barriers. ArIO, as a ligand, generates masked Fen═O species of the type Fe(n-2)-OIAr. Herein, we used gas-phase ion-molecule reactions and DFT calculations to explore the properties of masked iron-oxo species and to understand their unmasking mechanisms. The theory shows that the I-O bond cleavage in [(TPA)FeIVO(ArIO)]2+ (12+, TPA = tris(2-pyridylmethyl)amine)) is highly endothermic; therefore, it can be achieved only in collision-induced dissociation of 12+ leading to the unmasked iron(VI) dioxo complex. The reduction of 12+ by HAT leads to [(TPA)FeIIIOH(ArIO)]2+ with a reduced energy demand for the I-O bond cleavage but is, however, still endothermic. The exothermic unmasking of the Fe═O bond is predicted after one-electron reduction of 12+ or after OAT reactivity. The latter leads to the 4e- oxidation of unsaturated hydrocarbons: The initial OAT from [(TPA)FeIVO(ArIO)]2+ leads to the epoxidation of an alkene and triggers the unmasking of the second Fe═O bond still within one collisional complex. The second oxidation step starts with HAT from a C-H bond and follows with the rebound of the C-radical and the OH group. The process starting with the one-electron reduction could be studied with [(TQA)FeIVO(ArIO)]2+ (22+, TQA = tris(2-quinolylmethyl)amine)) because it has a sufficient electron affinity for electron transfer with alkenes. Accordingly, the reaction of 22+ with 2-carene leads to [(TQA)FeIIIO(ArIO)]2+ that exothermically eliminates ArI and unmasks the reactive FeV-dioxo species.

Spectroscopic Evidence for a Cobalt-Bound Peroxyhemiacetal Intermediate.

Aldehyde deformylation reactions by metal dioxygen adducts have been proposed to involve peroxyhemiacetal species as key intermediates. However, direct evidence of such intermediates has not been obtained to date. We report the spectroscopic characterization of a mononuclear cobalt(III)-peroxyhemiacetal complex, [Co(Me3-TPADP)(O2CH(O)CH(CH3)C6H5)]+ (2), in the reaction of a cobalt(III)-peroxo complex (1) with 2-phenylpropionaldehyde (2-PPA). The formation of 2 is also investigated by isotope labeling experiments and kinetic studies. The conclusion that the peroxyhemiacetalcobalt(III) intermediate is responsible for the aldehyde deformylation is supported by the product analyses. Furthermore, isotopic labeling suggests that the reactivity of the cobalt(III)-peroxo complex depends on the second reactant. The aldehyde inserts between the oxygen atoms of 1, whereas the reaction with acyl chlorides proceeds by a nucleophilic attack. The observation of the peroxyhemiacetal intermediate provides significant insight into the initial step of aldehyde deformylation by metalloenzymes.

Tuning the H-Atom Transfer Reactivity of Iron(IV)-Oxo Complexes as Probed by Infrared Photodissociation Spectroscopy.

Reactivities of non-heme iron(IV)-oxo complexes are mostly controlled by the ligands. Complexes with tetradentate ligands such as [(TPA)FeO]2+ (TPA=tris(2-pyridylmethyl)amine) belong to the most reactive ones. Here, we show a fine-tuning of the reactivity of [(TPA)FeO]2+ by an additional ligand X (X=CH3 CN, CF3 SO3- , ArI, and ArIO; ArI=2-(t BuSO2 )C6 H4 I) attached in solution and reveal a thus far unknown role of the ArIO oxidant. The HAT reactivity of [(TPA)FeO(X)]+/2+ decreases in the order of X: ArIO > MeCN > ArI ≈ TfO- . Hence, ArIO is not just a mere oxidant of the iron(II) complex, but it can also increase the reactivity of the iron(IV)-oxo complex as a labile ligand. The detected HAT reactivities of the [(TPA)FeO(X)]+/2+ complexes correlate with the Fe=O and FeO-H stretching vibrations of the reactants and the respective products as determined by infrared photodissociation spectroscopy. Hence, the most reactive [(TPA)FeO(ArIO)]2+ adduct in the series has the weakest Fe=O bond and forms the strongest FeO-H bond in the HAT reaction.

Core-shell PdCu bimetallic colloidal nanoparticles in Sonogashira cross-coupling reaction: mechanistic insights into the catalyst mode of action.

Core-shell PdCu nanoparticles with different metal proportions were synthesized using a one-pot methodology and characterized by STEM, HRTEM, XANES and EXAFS analysis. The bimetallic nanoparticles were applied as catalysts in the Sonogashira cross-coupling reaction to investigate the mode of action of the PdCu in the reaction. The copper content directly influenced the generation of the cross-coupling product, shaping the performance of the catalyst. A quasi-homogeneous reaction pathway was evidenced by kinetics and poisoning experiments as well as XAS, HRTEM and HRMS analysis. These findings help to elucidate the mode of action of the PdCu nanocatalysts in the, as yet, unrevealed Sonogashira mechanism and the potential development of new nanocatalysts.

The Intermediates in Lewis Acid Catalysis with Lanthanide Triflates.

Lanthanide triflates are effective Lewis acid catalysts in reactions involving carbonyl compounds due to their high oxophilicity and water stability. Despite the growing interest, the identity of the catalytic species formed in lanthanide catalysed reactions is still unknown. We have therefore used mass spectrometry and ion spectroscopy to intercept and characterize the intermediates in a reaction catalysed by ytterbium and dysprosium triflates. We were able to identify a number of lanthanide intermediates formed in a simple condensation reaction between a C-acid and an aldehyde. Results show correlation between the reactivity of lanthanide complexes and their charge state and suggest that the triply charged complexes play a key role in lanthanide catalysed reactions. Spectroscopic data of the gaseous ions accompanied by theoretical calculations reveal that the difference between catalytic efficiencies of ytterbium and dysprosium ions can be explained by their different electrophilicity.