Search

A new catalyst for the carboxylative synthesis of arylacetic and benzoic acids using formic acid (HCOOH) as the CO surrogate was developed. In an improvement over previous work, CO is generated in situ without the need for any additional activators. Key to success was the use of a specific system consisting of palladium acetate and 1,2-bis((tert-butyl(2-pyridinyl)phosphinyl)methyl)benzene. The generality of this method is demonstrated by the synthesis of more than 30 carboxylic acids, including non-steroidal anti-inflammatory drugs (NSAIDs), under mild conditions in good yields.

Methanol ist als Losungsmittel, als billiges Reagenz und als nachhaltiger Grundstock fur wertvolle Chemikalien, Pharmazeutika und Werkstoffe von Nutzen. Unter den verschiedenen Anwendungen ist der Gebrauch von Methanol als C1-Quelle fur die Bildung von C-C-, C-N- und C-O-Bindungen nach wie vor in der organischen Synthese und in der Arzneimittelforschung wichtig. Besonders die C-, N- und O-Methylierung ist von zentralem Interesse, weil die resultierenden Strukturmotive in Naturstoffen sowie in Fein- und Groschemikalien vorkommen. In diesem Minireview fassen wir die Nutzung von Methanol als C1-Quelle fur Methylierungen, Methoxylierungen, Formylierungen, Methoxycarbonylierungen und die oxidative Methylesterbildung zusammen.

A novel catalytic hydrogen-autotransfer protocol for the atom-efficient α-alkylation of ketones with readily available alcohols is presented. The use of manganese complexes bearing non-innocent PNP pincer ligands enabled the functionalization of a broad range of valuable ketones, including 2-oxindole, estrone 3-methyl ether, and testosterone. Mechanistic investigations suggest the participation of an intramolecular amidate-assisted alcohol-dehydrogenation process.

Metall-Nanopartikel, die auf N-dotierten Kohlenstoffmaterialien fixiert wurden, haben sich als neuartige Katalysatoren fur verschiedene organische Umwandlungen herausgestellt. In diesem Kurzaufsatz werden Strategien fur die Synthese von auf N-dotiertem Kohlenstoff fixierten Metallkompositen und ihre Charakterisierung nach neuestem Stand der Technik beschrieben. Die katalytischen Anwendungen dieser faszinierenden Materialien fur industriell relevante Reaktionen wie Oxidationen, Hydrierungen, die Fischer–Tropsch-Synthese und die H2-Entwicklung werden zusammengefasst. Zudem werden die Auswirkungen eines N-Einbaus in die verschiedenen katalytischen Systeme verdeutlicht.

A novel strategy for the synthesis of oxazolidin-2-ones from vicinal diols and urea is described. In this heterocycle synthesis, two different C-O and C-N bonds are sequentially formed in a domino process consisting of nucleophilic substitution and alcohol amination. The use of readily available starting materials and the good atom economy render this process environmentally benign. While this transformation is already highly chemo- and regioselective, we also developed the first asymmetric version of this method using (R)-(+)-MeO-BIPHEP as the chiral ligand.

Carbonylation reactions represent useful tools for organic synthesis. However, the necessity to use gaseous carbon monoxide is a disadvantage for most organic chemists. To solve this problem, novel protocols have been developed for conducting palladium-catalyzed reductive carbonylations of aryl bromides and alkoxycarbonylations using paraformaldehyde as an external CO source (CO gas free). Hence, aromatic aldehydes and esters were synthesized in moderate to good yields.

A new approach for the facile synthesis of fused quinazolinone scaffolds through a palladium-catalyzed carbonylative coupling followed by an intramolecular nucleophilic aromatic substitution is described. The base serves as the key modulator: Whereas DBU gives rise to the linear isomers, Et3N promotes the preferential formation of angular products. Interestingly, a light-induced 4+4 reaction of the product was also observed.

Given the importance of quinazolinones and carbonylative transformations, a palladium-catalyzed four-component carbonylative coupling system for the synthesis of diverse 4(3H)-quinazolinone in a concise and convergent fashion has been developed. Starting from 2-bromoanilines (1 mmol), trimethyl orthoformate (2 mmol), and amines (1.1 mmol), under 10 bar of CO, the desired products were isolated in good yields in the presence of Pd(OAc)2 (2 mol %), BuPAd2 (6 mol %) in 1,4-dioxane (2 mL) at 100 °C, using N,N-diisopropylethylamine (2 mmol) as the base. Notably, the process tolerates the presence of various reactive functional groups and is very selective for quinazolinones, and was used in the synthesis of the precursor to the bioactive dihydrorutaempine.

The first carbonylative Heck reactions of aryl and alkenyl triflate derivatives with carbon monoxide and aromatic olefins proceed in the presence of palladium catalysts generated in situ.

Selective functionalization reactions of aromatic and heteroaromatic halides with carbon, oxygen, and nitrogen nucleophiles have attracted much attention in the last decades. In addition to typical metal-catalyzed coupling reactions, direct functionalization of aryl halides through the formation of Grignard reagents offer new ways for the efficient construction of biologically interesting carboand heterocycles. Recent elegant examples include the development of LiClmediated preparation of Grignard reagents by Knochel and co-workers. Inspired by their work and our interest in functionalization reactions of aryl halides, we have been fascinated in the direct synthesis of aryl fluoride compounds from aryl Grignard reagents. Although a large number of known pharmaceutical and agrochemical products contain fluorinated arenes (Scheme 1), which enhance solubility, bioavailability, and metabolic stability compared with non-fluorinated analogues, there is no convenient and general synthetic method available for their synthesis. Commonly known methods for the introduction of a fluorine atom to arenes require relatively harsh reaction conditions. Typical examples include the direct fluorination of arenes, the Balz–Schiemann reaction of aryldiazonium salts with HBF4, and the so-called Halex exchange reaction of activated aryl halides with metal fluorides. In addition, transition-metal-promoted fluorinations have been achieved through the use of electrophilic N!F reagents such as Selectfluor or N-fluoropyridinium salts. Unfortunately, in most of these reactions stoichiometric amounts of the transition metal must be used or specific directing groups on the substrate are required. Most recently, Buchwald and co-workers developed an elegant palladium-catalyzed fluorination of aryl triflates using AgF or CsF. Our initial investigations aimed at the fluorination of 4bromoanisole (1), which is a particularly challenging substrate for nucleophilic fluorination, to give 4-fluoroanisole (2 ; Table 1). In our model reaction we converted 1 into the corresponding aryl Grignard 3 mediated by LiCl, according to the procedure developed by Krasovskiy and Knochel. We Scheme 1. Selected examples of therapeutically important aryl fluoride compounds.

Um eine CO-Gruppe reicher: (Hetero-)Arene sind aus der industriellen Herstellung von Agrochemikalien, Farbstoffen, Pharmaka etc. nicht wegzudenken. Wahrend der vergangenen Jahrzehnte wurden ubergangsmetallkatalysierte Kupplungen von Arylhalogeniden mit Nucleophilen aller Art entwickelt. Dieser Aufsatz fasst aktuelle Fortschritte auf dem Gebiet der palladiumkatalysierten Carbonylierungen von Arylhalogeniden und ahnlichen Verbindungen zusammen (siehe Schema). Palladiumkatalysierte Carbonylierungen von Arylhalogeniden in Gegenwart verschiedener Nucleophile haben sich seit ihrer Einfuhrung durch Heck und Mitarbeiter im Jahr 1974 schnell weiterentwickelt, sodass heute eine Vielzahl von Palladiumkatalysatoren fur unterschiedliche Carbonylierungsreaktionen verfugbar ist. Auf diesem Weg erhaltliche Carbonsaurederivate, Aldehyde und Ketone sind wichtige Zwischenstufen bei der industriellen Herstellung von Farbstoffen, Pharmaka, Agrochemikalien und anderen Produkten. In diesem Aufsatz werden aktuelle Ergebnisse aus der akademischen Forschung und erste industrielle Prozesse zusammengefasst.