Synthesis, Structure, and Reactivity of a Terminal Cadmium Hydride Compound, [κ3-TismPriBenz]CdH.

The terminal cadmium hydride compound, [κ3-TismPriBenz]CdH, which features the tris[(1-isopropylbenzimidazol-2-yl)dimethylsilyl]methyl ligand, may be obtained via the reactions of either [κ3-TismPriBenz]CdN(SiMe3)2 or [TismPriBenz]CdOSiPh3 with PhSiH3. The Cd-H bond of [κ3-TismPriBenz]CdH undergoes (a) metathesis reactions with MeI, Me3SiX (X = Cl, Br, I, NCO), and Me3SnX (X = Cl, Br, I) to afford the corresponding [TismPriBenz]CdX derivative, (b) insertion with CO2 and CS2 to afford respectively [TismPriBenz]Cd(κ1-O2CH) and [TismPriBenz]Cd(κ1-S2CH), and (c) hydride abstraction with B(C6F5)3 to afford {[TismPriBenz]Cd}[HB(C6F5)3] that possesses a rare trigonal monopyramidal geometry for cadmium.

Efficient Base-Free Aqueous Reforming of Methanol Homogeneously Catalyzed by Ruthenium Exhibiting a Remarkable Acceleration by Added Catalytic Thiol.

Production of H2 by methanol reforming is of particular interest due the low cost, ready availability, and high hydrogen content of methanol. However, most current methods either require very high temperatures and pressures or strongly rely on the utilization of large amounts of base. Here we report an efficient, base-free aqueous-phase reforming of methanol homogeneously catalyzed by an acridine-based ruthenium pincer complex, the activity of which was unexpectedly improved by a catalytic amount of a thiol additive. The reactivity of this system is enhanced by nearly 2 orders of magnitude upon addition of the thiol, and it can maintain activity for over 3 weeks, achieving a total H2 turnover number of over 130 000. On the basis of both experimental and computational studies, a mechanism is proposed which involves outer-sphere dehydrogenations promoted by a unique ruthenium complex with thiolate as an assisting ligand. The current system overcomes the need for added base in homogeneous methanol reforming and also highlights the unprecedented acceleration of catalytic activity of metal complexes achieved by the addition of a catalytic amount of thiol.

Homogeneous Reforming of Aqueous Ethylene Glycol to Glycolic Acid and Pure Hydrogen Catalyzed by Pincer-Ruthenium Complexes Capable of Metal-Ligand Cooperation.

Glycolic acid is a useful and important α-hydroxy acid that has broad applications. Herein, the homogeneous ruthenium catalyzed reforming of aqueous ethylene glycol to generate glycolic acid as well as pure hydrogen gas, without concomitant CO2 emission, is reported. This approach provides a clean and sustainable direction to glycolic acid and hydrogen, based on inexpensive, readily available, and renewable ethylene glycol using 0.5 mol % of catalyst. In-depth mechanistic experimental and computational studies highlight key aspects of the PNNH-ligand framework involved in this transformation.

Catalytic Hydrogenation of Thioesters, Thiocarbamates, and Thioamides.

Direct hydrogenation of thioesters with H2 provides a facile and waste-free method to access alcohols and thiols. However, no report of this reaction is documented, possibly because of the incompatibility of the generated thiol with typical hydrogenation catalysts. Here, we report an efficient and selective hydrogenation of thioesters. The reaction is catalyzed by an acridine-based ruthenium complex without additives. Various thioesters were fully hydrogenated to the corresponding alcohols and thiols with excellent tolerance for amide, ester, and carboxylic acid groups. Thiocarbamates and thioamides also undergo hydrogenation under similar conditions, substantially extending the application of hydrogenation of organosulfur compounds.

Metal-Ligand Cooperation Facilitates Bond Activation and Catalytic Hydrogenation with Zinc Pincer Complexes.

A series of PNP zinc pincer complexes capable of bond activation via aromatization/dearomatization metal-ligand cooperation (MLC) were prepared and characterized. Reversible heterolytic N-H and H-H bond activation by MLC is shown, in which hemilability of the phosphorus linkers plays a key role. Utilizing this zinc pincer system, base-free catalytic hydrogenation of imines and ketones is demonstrated. A detailed mechanistic study supported by computation implicates the key role of MLC in facilitating effective catalysis. This approach offers a new strategy for (de)hydrogenation and other catalytic transformations mediated by zinc and other main group metals.

Catalytic Oxidative Deamination by Water with H2 Liberation.

Selective oxidative deamination has long been considered to be an important but challenging transformation, although it is a common critical process in the metabolism of bioactive amino compounds. Most of the synthetic methods developed so far rely on the use of stoichiometric amounts of strong and toxic oxidants. Here we present a green and efficient method for oxidative deamination, using water as the oxidant, catalyzed by a ruthenium pincer complex. This unprecedented reaction protocol liberates hydrogen gas and avoids the use of sacrificial oxidants. A wide variety of primary amines are selectively transformed to carboxylates or ketones in good to high yields. It is noteworthy that mechanistic experiments and DFT calculations indicate that in addition to serving as the oxidant, water also plays an important role in assisting the hydrogen liberation steps involved in amine dehydrogenation.

Hydrogenative Depolymerization of Nylons.

The widespread crisis of plastic pollution demands discovery of new and sustainable approaches to degrade robust plastics such as nylons. Using a green and sustainable approach based on hydrogenation, in the presence of a ruthenium pincer catalyst at 150 °C and 70 bar H2, we report here the first example of hydrogenative depolymerization of conventional, widely used nylons and polyamides, in general. Under the same catalytic conditions, we also demonstrate the hydrogenation of a polyurethane to produce diol, diamine, and methanol. Additionally, we demonstrate an example where monomers (and oligomers) obtained from the hydrogenation process can be dehydrogenated back to a poly(oligo)amide of approximately similar molecular weight, thus completing a closed loop cycle for recycling of polyamides. Based on the experimental and density functional theory studies, we propose a catalytic cycle for the process that is facilitated by metal-ligand cooperativity. Overall, this unprecedented transformation, albeit at the proof of concept level, offers a new approach toward a cleaner route to recycling nylons.

Selective Conversion of Carbon Dioxide to Formaldehyde via a Bis(silyl)acetal: Incorporation of Isotopically Labeled C1 Moieties Derived from Carbon Dioxide into Organic Molecules.

The conversion of carbon dioxide to formaldehyde is a transformation that is of considerable significance in view of the fact that formaldehyde is a widely used chemical, but this conversion is challenging because CO2 is resistant to chemical transformations. Therefore, we report here that formaldehyde can be readily obtained from CO2 at room temperature via the bis(silyl)acetal, H2C(OSiPh3)2. Specifically, formaldehyde is released from H2C(OSiPh3)2 upon treatment with CsF at room temperature. H2C(OSiPh3)2 thus serves as a formaldehyde surrogate and provides a means to incorporate CHx (x = 1 or 2) moieties into organic molecules. Isotopologues of H2C(OSiPh3)2 may also be synthesized, thereby providing a convenient means to use CO2 as a source of isotopic labels in organic molecules.

Oxidizable Ketones: Persistent Radical Cations from the Single-Electron Oxidation of 2,3-Diaminocyclopropenones.

Single electron oxidation of 2,3-diaminocyclopropenones is shown to give rise to stable diaminocyclopropenium oxyl (DACO) radical cations. Cyclic voltammetry reveals reversible oxidations in the range of +0.70-1.10 V (vs. SCE). Computational, EPR, and X-ray analysis support the view that the oxidized species is best described as a cyclopropenium ion with spin density located on the heteroatom substituents, including 23.5 % on oxygen. The metal-ligand behavior of the DACO radical is also described.

Electrophotocatalysis with a Trisaminocyclopropenium Radical Dication.

Visible-light photocatalysis and electrocatalysis are two powerful strategies for the promotion of chemical reactions. Here, these two modalities are combined in an electrophotocatalytic oxidation platform. This chemistry employs a trisaminocyclopropenium (TAC) ion catalyst, which is electrochemically oxidized to form a cyclopropenium radical dication intermediate. The radical dication undergoes photoexcitation with visible light to produce an excited-state species with oxidizing power (3.33 V vs. SCE) sufficient to oxidize benzene and halogenated benzenes via single-electron transfer (SET), resulting in C-H/N-H coupling with azoles. A rationale for the strongly oxidizing behavior of the photoexcited species is provided, while the stability of the catalyst is rationalized by a particular conformation of the cis-2,6-dimethylpiperidine moieties.

Insertion of Isonitriles into the M-C Bonds of Group 4 Dialkyl Complexes.

The 2,3-dimethylbutadiene complexes of Group 4 metals with constrained geometry (cg) ligands have been prepared and found to adopt a supine orientation with σ2,π bonding. Treatment of cgTi(2,3-dimethylbutadiene) (1-Ti) with tBuNC leads to the formation of a titana-aziridine (3) with a coordinated cyclopentenimine that arises from the formal [4+1] addition of the diene to the isonitrile. In contrast, the reactions of cgZr(2,3-dimethylbutadiene) (1-Zr) or cgHf(2,3-dimethylbutadiene) (1-Hf) with 2 equiv of tBuNC or XyNC proceeded in a more sophisticated manner to yield unsymmetrical 2,5-diazametallacyclopentane derivatives (4, 6-Zr, and 6-Hf) or symmetrical 2,5-diazametallacyclopentene complexes (7-Zr and 7-Hf). The unsymmetrical products contain coordinated cyclopropanes; the strength of the interaction is measured by the reduction in the 1 JCC of the C-C bond that is coordinated. A detailed mechanistic analysis has been possible with the related cgM(Me)2 (M = Ti and Hf) complexes. The first insertion is too fast to monitor, but allows complete conversion to an alkyl iminoacyl intermediate. The second isonitrile (RNC) may react with that intermediate by either of two different mechanisms, reductive elimination and coordination/insertion. In the first mechanism (Ti), rate-determining C-C coupling gives a titana-aziridine, followed by fast coordination of the isonitrile. In the second mechanism (Hf), coordination is the slow step; insertion to form a bis(iminoacyl) Hf complex is rapid.

Zinc and Magnesium Catalysts for the Hydrosilylation of Carbon Dioxide.

The terminal zinc and magnesium hydride compounds, [κ3-TismPriBenz]ZnH and [TismPriBenz]MgH, which feature the tris[(1-isopropylbenzimidazol-2-yl)dimethylsilyl]methyl ligand, react with B(C6F5)3 to afford the ion pairs, {[TismPriBenz]M}[HB(C6F5)3] (M = Zn, Mg), which are rare examples of these metals in trigonal monopyramidal coordination environments. Significantly, in combination with B(C6F5)3, {[TismPriBenz]M}-[HB(C6F5)3] generates catalytic systems for the hydrosilylation of CO2 by R3SiH to afford sequentially the bis(silyl)acetal, H2C(OSiR3)2, and CH4 (R3SiH = PhSiH3, Et3SiH, and Ph3SiH). In contrast to many other catalysts for these transformations, both the zinc and magnesium catalytic systems are active at room temperature, and the latter provides the first example of catalytic hydrosilylation of CO2 involving a magnesium compound. Also of note, the selectivity of the catalytic systems may be controlled by the nature of the silane, with PhSiH3 favoring CH4, and Ph3SiH favoring the bis(silyl)acetal, H2C(OSiPh3)2.

Synthesis, Structure, and Reactivity of a Terminal Magnesium Hydride Compound with a Carbatrane Motif, [TismPriBenz]MgH: A Multifunctional Catalyst for Hydrosilylation and Hydroboration.

The tris[(1-isopropylbenzimidazol-2-yl)dimethylsilyl)]methyl ligand, [TismPriBenz], has been employed to form the magnesium carbatrane compound, [TismPriBenz]MgH, which possesses a terminal hydride ligand. Specifically, [TismPriBenz]MgH is obtained via the reaction of [TismPriBenz]MgMe with PhSiH3. The reactivity of [TismPriBenz]MgMe and [TismPriBenz]MgH allows access to a variety of other structurally characterized carbatrane derivatives, including [TismPriBenz]MgX [X = F, Cl, Br, I, SH, N(H)Ph, CH(Me)Ph, O2CMe, S2CMe]. In addition, [TismPriBenz]MgH is a catalyst for (i) hydrosilylation and hydroboration of styrene to afford the Markovnikov products, Ph(Me)C(H)SiH2Ph and Ph(Me)C(H)Bpin, and (ii) hydroboration of carbodiimides and pyridine to form N-boryl formamidines and N-boryl 1,4- and 1,2-dihydropyridines, respectively.

Prognostic impact of intraocular involvement in primary CNS lymphoma: experience from the G-PCNSL-SG1 trial.

The impact of intraocular involvement (IOL) in primary CNS lymphoma (PCNSL) has not been sufficiently evaluated. Here, we present the analysis of IOL in the only completed randomized phase III trial in PCNSL. The G-PCNSL-SG1 study evaluated the role of whole-brain radiotherapy in primary therapy of PCNSL. Data of the 526 eligible study patients were checked, and clinical characteristics, therapy, and outcome of patients with IOL diagnosed at study inclusion were analyzed. Ophthalmologic examination at study inclusion was performed in 297 patients (56.5 %) of whom IOL was diagnosed in 19 (6.4 %). Clinical characteristics did not significantly differ between patients with IOL (IOL+) and those without (IOL-). The median progression-free survival (PFS) in the IOL+ group was 3.5 months (95 % CI 0.0-7.07) as compared to 8.3 months (95 % CI 4.78-11.78) in the IOL- group (P = 0.004), the median overall survival (OS) was 13.2 months (95 % CI 0.86-25.62) and 20.5 months (95 % CI 15.56-25.5), respectively (P = 0.155). In multivariate analysis, a significantly inferior PFS and OS for IOL+ patients were found. IOL at diagnosis of PCNSL was an independent negative prognostic indicator for PFS and OS in this analysis.

Case report: Cerebral amyloid angiopathy-related inflammation in a patient with granulomatosis with polyangiitis.

Background: Cerebral amyloid angiopathy-related inflammation (CAA-ri) defines a subacute autoimmune encephalopathy, which is presumably caused by increased CSF concentrations of anti-Aß autoantibodies. This autoinflammatory reaction is temporally and regionally associated with microglial activation, inflammation and radiological presence of vasogenic edema. Clinical characteristics include progressive demential development as well as headache and epileptic seizures. In the absence of histopathologic confirmation, the criteria defined by Auriel et al. allow diagnosis of probable resp. possible CAA-ri. CAA-ri shows responsiveness to immunosuppressive therapies and a possible coexistence with other autoinflammatory diseases. Methods: We present a case report and literature review on the diagnosis of CAA-ri in a patient with known granulomatosis with polyangiitis (GPA). Results: Initially, the presented patient showed neuropsychiatric abnormalities and latent arm paresis. Due to slight increase in CSF cell count, an initial antiviral therapy was started. MR tomography showed a pronounced frontotemporal edema as well as cerebral microhemorrhages, leading to the diagnosis of CAA-ri. Subsequent high-dose steroid treatment followed by six intravenous cyclophosphamide pulses resulted in decreased CSF cell count and regression of cerebral MRI findings. Conclusion: The symptoms observed in the patient are consistent with previous case reports on CAA-ri. Due to previously known GPA, we considered a cerebral manifestation of this disease as a differential diagnosis. However, absence of pachymeningitis as well as granulomatous infiltrations on imaging made cerebral GPA less likely. An increased risk for Aß-associated pathologies in systemic rheumatic diseases is discussed variously.

Measuring Higgs couplings from LHC data.

Following recent ATLAS and CMS publications we interpret the results of their Higgs searches in terms of standard model operators. For a Higgs boson mass of 125 GeV we determine several Higgs couplings from published 2011 data and extrapolate the results towards different scenarios of LHC running. Even though our analysis is limited by low statistics we already derive meaningful constraints on modified Higgs sectors.

Dehydrogenative ester synthesis from enol ethers and water with a ruthenium complex catalyzing two reactions in synergy.

We report the dehydrogenative synthesis of esters from enol ethers using water as the formal oxidant, catalyzed by a newly developed ruthenium acridine-based PNP(Ph)-type complex. Mechanistic experiments and density functional theory (DFT) studies suggest that an inner-sphere stepwise coupled reaction pathway is operational instead of a more intuitive outer-sphere tandem hydration-dehydrogenation pathway.

High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial.

BACKGROUND: High-dose methotrexate is the standard of care for patients with newly diagnosed primary CNS lymphoma. The role of whole brain radiotherapy is controversial because delayed neurotoxicity limits its acceptance as a standard of care. We aimed to investigate whether first-line chemotherapy based on high-dose methotrexate was non-inferior to the same chemotherapy regimen followed by whole brain radiotherapy for overall survival. METHODS: Immunocompetent patients with newly diagnosed primary CNS lymphoma were enrolled from 75 centres and treated between May, 2000, and May, 2009. Patients were allocated by computer-generated block randomisation to receive first-line chemotherapy based on high-dose methotrexate with or without subsequent whole brain radiotherapy, with stratification by age (<60 vs ≥60 years) and institution (Berlin vs Tübingen vs all other sites). The biostatistics centre assigned patients to treatment groups and informed local centres by fax; physicians and patients were not masked to treatment group after assignment. Patients enrolled between May, 2000, and August, 2006, received high-dose methotrexate (4 g/m(2)) on day 1 of six 14-day cycles; thereafter, patients received high-dose methotrexate plus ifosfamide (1·5 g/m(2)) on days 3-5 of six 14-day cycles. In those assigned to receive first-line chemotherapy followed by radiotherapy, whole brain radiotherapy was given to a total dose of 45 Gy, in 30 fractions of 1·5 Gy given daily on weekdays. Patients allocated to first-line chemotherapy without whole brain radiotherapy who had not achieved complete response were given high-dose cytarabine. The primary endpoint was overall survival, and analysis was per protocol. Our hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival, with a non-inferiority margin of 0·9. This trial is registered with ClinicalTrials.gov, number NCT00153530. FINDINGS: 551 patients (median age 63 years, IQR 55-69) were enrolled and randomised, of whom 318 were treated per protocol. In the per-protocol population, median overall survival was 32·4 months (95% CI 25·8-39·0) in patients receiving whole brain radiotherapy (n=154), and 37·1 months (27·5-46·7) in those not receiving whole brain radiotherapy (n=164), hazard ratio 1·06 (95% CI 0·80-1·40; p=0·71). Thus our primary hypothesis was not proven. Median progression-free survival was 18·3 months (95% CI 11·6-25·0) in patients receiving whole brain radiotherapy, and 11·9 months (7·3-16·5; p=0·14) in those not receiving whole brain radiotherapy. Treatment-related neurotoxicity in patients with sustained complete response was more common in patients receiving whole brain radiotherapy (22/45, 49% by clinical assessment; 35/49, 71% by neuroradiology) than in those who did not (9/34, 26%; 16/35, 46%). INTERPRETATION: No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma, but our primary hypothesis was not proven. The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors.

Highly Efficient Additive-Free Dehydrogenation of Neat Formic Acid.

Formic acid (FA) is a promising hydrogen carrier which can play an instrumental role in the overall implementation of a hydrogen economy. In this regard, it is important to generate H2 gas from neat FA without any solvent/additive, for which existing systems are scarce. Here we report the remarkable catalytic activity of a ruthenium 9H-acridine pincer complex for this process. The catalyst is unusually stable and robust in FA even at high temperatures and can catalyse neat FA dehydrogenation for over a month, with a total turnover number of 1,701,150, while also generating high H2/CO2 gas pressures (tested up to 100 bars). Mechanistic investigations and DFT studies are conducted to fully understand the molecular mechanism to the process. Overall, the high activity, stability, selectivity, simplicity and versatility of the system to generate a CO-free H2/CO2 gas stream and high pressure from neat FA makes it promising for large-scale implementation.

Mechanistic Investigations of Ruthenium Catalyzed Dehydrogenative Thioester Synthesis and Thioester Hydrogenation.

We have recently reported the previously unknown synthesis of thioesters by coupling thiols and alcohols (or aldehydes) with liberation of H2, as well as the reverse hydrogenation of thioesters, catalyzed by a well-defined ruthenium acridine-9H based pincer complex. These reactions are highly selective and are not deactivated by the strongly coordinating thiols. Herein, the mechanism of this reversible transformation is investigated in detail by a combined experimental and computational (DFT) approach. We elucidate the likely pathway of the reactions, and demonstrate experimentally how hydrogen gas pressure governs selectivity toward hydrogenation or dehydrogenation. With respect to the dehydrogenative process, we discuss a competing mechanism for ester formation, which despite being thermodynamically preferable, it is kinetically inhibited due to the relatively high acidity of thiol compared to alcohol and, accordingly, the substantial difference in the relative stabilities of a ruthenium thiolate intermediate as opposed to a ruthenium alkoxide intermediate. Accordingly, various additional reaction pathways were considered and are discussed herein, including the dehydrogenative coupling of alcohol to ester and the Tischenko reaction coupling aldehyde to ester. This study should inform future green, (de)hydrogenative catalysis with thiols and other transformations catalyzed by related ruthenium pincer complexes.