Hydrogenative Cyclopropanation and Hydrogenative Metathesis

The unusual geminal hydrogenation of a propargyl alcohol derivative with [CpXRuCl] as the catalyst entails formation of pianostool ruthenium carbenes in the first place; these reactive intermediates can be intercepted with tethered alkenes to give either cyclopropanes or cyclic olefins as the result of a formal metathesis event. The course of the reaction is critically dependent on the substitution pattern of the alkene trap

Light-Driven Alkyne gem-Hydrogenation: An Intramolecular Approach to Hoveyda–Grubbs Catalysts

The light-driven gem-hydrogenation of internal alkynes in the presence of [(NHC)(η6-cymene)RuCl2] generates discrete ruthenium carbene complexes. When applied to appropriately designed enyne substrates, the reactive intermediates thus formed will engage the tethered olefin in metathetic ring closure while splitting off a Hoveyda–Grubbs-type complex as secondary carbene. This unconventional approach to these classical catalysts for olefin metathesis rivals existing methodology in that it is safe, short, phosphine-free, and uses readily available starting materials

Hydrogenative Cycloisomerization and Sigmatropic Rearrangement Reactions of Cationic Ruthenium Carbenes Formed by Catalytic Alkyne gem-Hydrogenation

gem-Hydrogenation of propargyl alcohol derivatives with [CpXRu(MeCN)3]PF6 (CpX=substituted cyclopentadienyl) as catalysts affords cationic pianostool ruthenium carbene complexes which are so electrophilic that they attack a tethered olefin to furnish cyclopentene products; cyclopropanation or metathesis do not compete with this novel transformation. If the transient carbenes carry appropriate propargylic substituents, however, they engage in ([2,3]-sigmatropic) rearrangements to give enol esters (carbonates, carbamates, sulfonates) or alkenyl halides. Both pathways are unprecedented in the vast hydrogenation literature. The proposed mechanistic scenarios are in line with labeling experiments and spectroscopic data; most notably, PHIP NMR spectroscopy (PHIP=parahydrogen induced polarization) provides compelling evidence that the reactions are indeed triggered by highly unorthodox gem-hydrogenation events

Alkyne gem‐Hydrogenation: Formation of Pianostool Ruthenium Carbene Complexes and Analysis of Their Chemical Character

Parahydrogen (p‐H2) induced polarization (PHIP) NMR spectroscopy showed that [CpXRu] complexes with greatly different electronic properties invariably engage propargyl alcohol derivatives into gem‐hydrogenation with formation of pianostool ruthenium carbenes; in so doing, less electron rich CpX rings lower the barriers, stabilize the resulting complexes and hence provide opportunities for harnessing genuine carbene reactivity. The chemical character of the resulting ruthenium complexes was studied by DFT‐assisted analysis of the chemical shift tensors determined by solid‐state 13C NMR spectroscopy. The combined experimental and computational data draw the portrait of a family of ruthenium carbenes that amalgamate purely electrophilic behavior with characteristics more befitting metathesis‐active Grubbs‐type catalysts

Inhaled ciclesonide versus inhaled budesonide or inhaled beclomethasone or inhaled fluticasone for chronic asthma in adults: a systematic review

BACKGROUND: Ciclesonide is a new inhaled corticosteroids licensed for the prophylactic treatment of persistent asthma in adults. Currently beclomethasone dipropionate, budesonide and fluticasone propionate are the most commonly prescribed inhaled corticosteroids for the treatment of asthma but there has been no systematic review comparing the effectiveness and safety ciclesonide to these agents. We therefore aimed to systematically review published randomised controlled trials of the effectiveness and safety of ciclesonide compared to alternative inhaled corticosteroids in people with asthma. METHODS: We performed literature searches on MEDLINE, EMBASE, PUBMED, the COCHRANE LIBRARY and various Internet evidence sources for randomised controlled trials or systematic reviews comparing ciclesonide to beclomethasone or budesonide or fluticasone in adult humans with persistent asthma. Data was extracted by one reviewer. RESULTS: Five studies met the inclusion criteria. Methodological quality was variable. There were no trials comparing ciclesonide to beclomethasone. There was no significant difference between ciclesonide and budesonide or fluticasone on the following outcomes: lung function, symptoms, quality of life, airway responsiveness to a provoking agent or inflammatory markers. However, the trials were very small in size, increasing the possibility of a type II error. One trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 47% of that of budesonide while another trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 53% of that of fluticasone. One trial demonstrated less suppression of cortisol in overnight urine collection after ciclesonide compared to fluticasone (geometric mean fold difference = 1.5, P < 0.05) but no significant difference in plasma cortisol response. CONCLUSION: There is very little evidence comparing CIC to other ICS, restricted to very small, phase II studies of low power. These demonstrate CIC has similar effectiveness and efficacy to FP and BUD (though equivalence is not certain) and findings regarding oral deposition and HPA suppression are inconclusive. There is no direct comparative evidence that CIC causes fewer side effects since none of the studies reported patient-based outcomes

Ruthenium-vermittelte geminale Hydrierung von Alkinen

Die Ruthenium-vermittelte geminale Hydrierung von Alkinen ist eine konzeptionell neue Reaktivität in der Hydrierungschemie, bei der zwei Wasserstoffatome auf ein und das selbe Kohlenstoffatom eines Alkins übertragen werden. In der Folge entsteht ein Rutheniumcarbenkomplex, der für katalytische Transformationen genutzt werden kann (Schema 1). Die ersten Studien zur gem-Hydrierung wurden mit [Cp*Ru]-basierten Komplexen durchgeführt. Diese Reaktivität ist mechanistisch eng mit der trans-Hydrierung eines Alkins verknüpft, die in katalytischen Anwendungen einen konkurrierenden Prozess darstellt. Mithilfe von PHIP-NMR- Studien wurde gezeigt, dass die relativen Barrieren zugunsten der gem-Hydrierung verschoben werden, wenn elektronenarme [CpXRu]-Komplexe verwendet werden. Dieses Prinzip konnte erfolgreich in der Katalyse angewendet werden, um den Umfang von [Cp*Ru]-katalysierten Reaktionen zu erweitern (Schema 2). Weiterhin konnte gezeigt werden, dass kationische [CpXRu]-Carbenkomplexe aus der gem-Hydrierung inhärent unterschiedliche Reaktivitäten als ihre neutralen Analoga aufweisen, was zur Entwicklung von zwei neuen katalytischen Reaktionen führte (Schema 3). Dass die gem-Hydrierung mit [CpXRu]-Systemen keine Singularität darstellt, konnte anhand der Entwicklung eines neuen Katalysatorsystems demonstriert werden. Unter Bestrahlung mit UV-A Licht initiieren [(NHC)(η6-cymol)RuCl2]-Komplexe eine hydrierende Metathese von Eninen zu cyclischen Olefinen. Die intermediären Carbenkomplexe sind vom Grubbs-Typ, wie eindeutig durch die vollständige Charakterisierung eines Hoveyda-Grubbs-artigen Komplexes bewiesen wurde (Schema 4). Detaillierte mechanistische Studien lieferten interessante Einblicke in das Reaktionsgeschehen und legen unter anderem nahe, dass der Rutheniumkatalysator in unterschiedlichen Spinzuständen durch den Katalysecyclus manövriert. Zuletzt wurden Hydridkomplexe als Zersetzungsprodukte des [(NHC)(η6-cymol)RuCl2]-Katalysators identifiziert, die einen Startpunkt für zukünftige Reaktionsoptimierung eröffnen. Einer dieser Hydridkomplexe ist wahrscheinlich der erste, vollständig charakterisierte anionische σ-H-Rutheniumkomplex

Grubbs Metathesis Enabled by a Light‐Driven gem‐Hydrogenation of Internal Alkynes

[(NHC)(cymene)RuCl2] (NHC = N‐heterocyclic carbene) complexes instigate a light‐driven gem‐hydrogenation of internal alkynes with concomitant formation of discrete Grubbs‐type ruthenium carbene species. This unorthodox reactivity mode is harnessed in form of a “hydrogenative metathesis” reaction, which converts an enyne substrate into a cyclic alkene. The intervention of ruthenium carbenes formed in the actual gem‐hydrogenation step was proven by the isolation and crystallographic characterization of a rather unusual representative of this series carrying an unconfined alkyl group on a disubstituted carbene center