A versatile catalyst system for enantioselective synthesis of 2-substituted 1,4-benzodioxanes

Abstract

IrCl/BIDIME-dimer catalyzed hydrogenation is reported for enantioselective synthesis of 2-substituted 1,4-benzodioxanes.

Nitro and Other Electron Withdrawing Group Activated Ruthenium Catalysts for Olefin Metathesis Reactions

“…[144] This is,o f course,f ully understandable in academic research, and even justified at the early stages of the industrial R&D work, but sooner or later the loading must be substantially reduced to make the production process economically viable.S ome examples where the amount of catalyst used was reduced from amultiple molar percent to its decimal fractions or even to ppm levels was achieved, thanks to the cooperation with the catalyst producer or metathesis expert, have been presented in this Review. [98,106,120] In this context, recent results by Nascimento and Fogg are quoted again, as they were able to prove that lowering the loading of the CAAC nitro catalyst is not only favorable from an economic point of view,b ut in fact it also increases the catalystss tability,b y inhibiting the bimolecular decomposition pathway. [136] This result shows yet again the importance of fundamental studies to deepen our understanding of the factors that influence the stability and activity of catalysts.I nt he practice of total synthesis leading to complex polyfunctional natural products and in medicinal chemistry,the prediction of the most optimal catalyst for ag iven substrate is not an otiose question but rather as erious problem.…”

“…Researchers at Boehringer Ingelheim Pharmaceuticals and Astatech BioPharmaceutical Corporation, supported by experts on olefin metathesis from Apeiron Synthesis S.A., reported the stereoselective synthesis of substituted 1,4benzodioxanes that are structural motifs of several drugs. [120] As the pharmaceutical industry has to keep the chemical production process as competitive and as cost-effective as possible,alot of effort was invested in optimizing each of the individual reaction steps.RCM of substrates containing vinyl ethers is known to be problematic, and ah igh loading of the second-generation Grubbs catalyst (5-8 mol %) was previously reported for the synthesis of 1,4-benzodioxines, [121] which hindered the practicality of this transformation. Gratifyingly,amounts of nitro catalyst Ru12 as low as 150 to 300 ppm were found to lead to the target 1,4-benzodioxanes in > 80 %y ield (Scheme 19).…”

“…Researchers at Boehringer Ingelheim Pharmaceuticals and Astatech BioPharmaceutical Corporation, supported by experts on olefin metathesis from Apeiron Synthesis S.A., reported the stereoselective synthesis of substituted 1,4‐benzodioxanes that are structural motifs of several drugs [120] . As the pharmaceutical industry has to keep the chemical production process as competitive and as cost‐effective as possible, a lot of effort was invested in optimizing each of the individual reaction steps.…”

Durch Nitro‐ und andere elektronenziehende Gruppen aktivierte Ruthenium‐Katalysatoren für die Olefinmetathese

“…Wissenschaftler von Boehringer Ingelheim Pharmaceuticals und Astatech BioPharmaceutical Corporation, unterstützt von Experten für Olefinmetathesen der Firma Apeiron Synthesis S. A., berichteten über die stereoselektive Synthese von substituierten 1,4‐Benzodioxanen, welche als Strukturmotive verschiedener Medikamente dienen [120] . Da die pharmazeutische Industrie den chemischen Produktionsprozess so konkurrenzfähig und kostengünstig wie möglich gestalten muss, wurde jeder einzelne Reaktionsschritt aufwendig optimiert.…”

“…Jedoch muss die Katalysatorbeladung früher oder später drastisch reduziert werden, um den Prozess wirtschaftlich tragbar zu gestalten. Einige Beispiele, in denen die Verringerung der verwendeten Katalysatormenge von mehreren mol % zu einem Bruchteil, oder sogar auf ppm‐Niveau, dank der Zusammenarbeit der Katalysatorhersteller oder Metathese‐Experten erreicht wurde, sind in diesem Aufsatz vorgestellt worden [98, 106, 120] . In diesem Zusammenhang soll an die jüngsten Ergebnisse von Fogg erinnert werden, in der sie beweisen konnte, dass die Senkung der CAAC‐Nitro‐Katalysatorbeladung nicht nur von einem wirtschaftlichen Standpunkt vorteilhaft ist, sondern auch die Stabilität des Katalysators durch Hemmung der bimolekularen Zersetzung erhöht [136] .…”