On the fundamentals and the use of tripodal tris(silanolate) ligands
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Date
2025
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Air-stable alkyne metathesis catalysts & Lewis acids for menthol synthesis
Abstract
Die Alkinmetathese ist eine Reaktion von strategischem Wert für die Naturstoffsynthese. Ihrer Anwendung wurde bisher durch den Mangel an leicht verfügbaren und stabilen Katalysatoren behindert. Eine neue Generation von Alkinmetathese Katalysatoren wurde mit dem Ziel entwickelt diese Beeinträchtigung zu überwinden. Die vorgestellten Molybdän-Alkylidin-Komplexe mit neuartigen tripodalen Tris(silanolat)-Liganden zeichnen sich durch eine beispiellose Stabilität und Nutzerfreundlichkeit aus, ohne dabei die Vorzüge früherer Katalysatorgenerationen einzubüßen.
Der Schlüssel zum Erfolg lag in der Kombination mehrere Designelemente, darunter das flexiblere tripodale Ligandengerüst sowie ein externer stabilisierender Ligand. Das entsprechende Addukt konnte im Gramm-Maßstab hergestellt werden und lässt sich routinemäßig an der Luft handhaben. In Lösung ist der zusätzliche Ligand jedoch labil und gibt bei Raumtemperatur durch spontane Dissoziation den aktiven Katalysator frei. Über eine standardisierte Testreaktion wurde die katalytische Aktivität der neuen Komplexe mit einer Reihe von Katalysatoren aus vorhergehenden Generationen verglichen. Zudem wurde erstmals auch die Luftstabilität der Komplexe untersucht. Das Addukt bleibt über viele Monate hinweg an Luft intakt und übertrifft damit alle bisherigen Hochleistungskatalysatoren. Darüber hinaus hat es ein ausgezeichnetes Anwendungsprofil, welches durch eine Reihe von anspruchsvollen Ringschlussreaktionen aus der Naturstoffsynthese demonstriert werden konnte.
Im zweiten Teil dieser Arbeit wurden explorative Untersuchungen zur Koordinationschemie einer besonderen Klasse tridentater Silanolat-Liganden vorgenommen. Die ‚Canopy-Liganden‘ zeichnen sich durch ihre starke Präferenz für eine C3-symmetrische Konformation aus. Aus diesem Grund sind sie für die Herstellung von Komplexen von Interesse, die an Metallzentren auf Kieselgeloberflächen in der heterogenen Katalyse erinnern.
Das Potential der erhaltenen Komplexe für Anwendungen in der Katalyse wurde anhand der Zyklisierung von Citronellal zu Isopulegol veranschaulicht. Die für die (industrielle) Synthese von (−)-Menthol interessante Reaktion verläuft mir guter Diastereoselektivität und ausgezeichneter Chemoselektivität. Die Temperaturstabilität des eingesetzten Komplexes übertrifft das bisherige Standard-Katalysatorsystem der Industrie und ermöglicht es, das Produkt und den Katalysator durch Destillation voneinander zu trennen.
Alkyne metathesis is a reaction of high strategic value in the synthesis of natural products. Widespread use of the transformation has been hampered by the lack of easily accessible and stable catalysts. A new generation of alkyne metathesis catalysts is presented that addresses the issue. The molybdenum alkylidyne complexes, comprising a novel tripodal tris(silanolate) ligand, are distinguished by an unprecedented level of stability and practicality without sacrificing the chemical virtues of their predecessors. Key to the success was a combination of features, including the design of a more flexible tripodal ligand scaffold and the addition of an external stabilizing ligand. The adduct could be prepared on gram scale and can be routinely handled in air. In solution at ambient temperature the additional ligand is labile and reveals the active catalyst by spontaneous dissociation. Its activity was benchmarked in a standardized reaction against a library of catalysts from previous generations. For the first time, these complexes were also compared with respect to their stability in air. The novel complex remained intact on the bench for many months, outperforming all previous highly-active catalysts. The adduct’s excellent performance in catalysis is highlighted in a row of challenging ring-closing alkyne metathesis reactions from natural product syntheses. The second part of the thesis contains an exploratory study of the coordination chemistry of a special class of tripodal tris(silanolate) ligands. The ‘canopy ligands’ are characterized by their preorganization into a C3 symmetrical conformation. For this reason, they are considered to be of interest for forming complexes reminiscent of metal sites supported on silica in heterogeneous catalysis. The synthesis of a library of complexes containing seven different metals and metalloids in varying oxidation states is reported, vividly illustrating the adaptability of the ‘canopy ligands’. The potential of the novel complexes for catalysis is demonstrated in the cyclization of citronellal to isopulegol. The reaction is of relevance to the (industrial) synthesis of (−)-menthol and proceeds with good diastereoselectivity and excellent chemoselectivity. The stability of the concerning aluminum complex at elevated temperatures is superior to the current standard catalysts and allows for a separation of product and catalyst via distillation.
Alkyne metathesis is a reaction of high strategic value in the synthesis of natural products. Widespread use of the transformation has been hampered by the lack of easily accessible and stable catalysts. A new generation of alkyne metathesis catalysts is presented that addresses the issue. The molybdenum alkylidyne complexes, comprising a novel tripodal tris(silanolate) ligand, are distinguished by an unprecedented level of stability and practicality without sacrificing the chemical virtues of their predecessors. Key to the success was a combination of features, including the design of a more flexible tripodal ligand scaffold and the addition of an external stabilizing ligand. The adduct could be prepared on gram scale and can be routinely handled in air. In solution at ambient temperature the additional ligand is labile and reveals the active catalyst by spontaneous dissociation. Its activity was benchmarked in a standardized reaction against a library of catalysts from previous generations. For the first time, these complexes were also compared with respect to their stability in air. The novel complex remained intact on the bench for many months, outperforming all previous highly-active catalysts. The adduct’s excellent performance in catalysis is highlighted in a row of challenging ring-closing alkyne metathesis reactions from natural product syntheses. The second part of the thesis contains an exploratory study of the coordination chemistry of a special class of tripodal tris(silanolate) ligands. The ‘canopy ligands’ are characterized by their preorganization into a C3 symmetrical conformation. For this reason, they are considered to be of interest for forming complexes reminiscent of metal sites supported on silica in heterogeneous catalysis. The synthesis of a library of complexes containing seven different metals and metalloids in varying oxidation states is reported, vividly illustrating the adaptability of the ‘canopy ligands’. The potential of the novel complexes for catalysis is demonstrated in the cyclization of citronellal to isopulegol. The reaction is of relevance to the (industrial) synthesis of (−)-menthol and proceeds with good diastereoselectivity and excellent chemoselectivity. The stability of the concerning aluminum complex at elevated temperatures is superior to the current standard catalysts and allows for a separation of product and catalyst via distillation.
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Table of contents
Keywords
Alkin-Metathese, Luftstabil, Katalyse, Silanol-Liganden, Zyklisierung
Subjects based on RSWK
Metathese <Chemie>, Alkine