Palladium/di-1-adamantyl-n-butylphosphine-catalyzed Carbonylation Reactions

Within this thesis several homogeneous palladium-catalyzed carbonylation reactions in the presence of carbon monoxide were investigated. In the course of our studies, the superior performance of the catalyst system palladium acetate/di-1-adamantyl-n-butylphosphine (cataCXium® A) in comparison to established palladium catalysts was demonstrated for both reductive carbonylations and alkoxycarbonylations of aryl and vinyl bromides. Hence, a variety of (hetero)aromatic aldehydes and carboxylic acid derivatives (esters, amides, acids) were successfully synthesized, among them novel biologically interesting indolylmaleimides. Furthermore, an efficient method for the synthesis of non-steroidal anti-inflammatory drugs such as ketoprofen and suprofen was developed.In der vorliegenden Dissertation wurden verschiedene, homogen palladiumkatalysierte Carbonylierungsreaktionen in Gegenwart von Kohlenmonoxid untersucht. Dabei konnte gezeigt werden, dass das System Palladiumacetat/Di-1-adamantyl-n-butylphosphin (cataCXium® A) sowohl in der reduktiven Carbonylierung als auch in der Alkoxycarbonylierung von Aryl- und Vinylbromiden die bekannten Palladium-Katalysator-Systeme an Aktivität, Selektivität und Produktivität übertrifft. Eine Vielzahl von (hetero)aromatischen Aldehyden und Carbonsäurederivaten (Ester, Amide, Säuren) konnte erfolgreich hergestellt werden, darunter auch bisher nicht beschriebene biologisch interessante Indolylmaleinimide. Darüber hinaus wurde im Rahmen dieser Arbeit eine effiziente Methode zur Synthese von nicht-steroidalen, entzündungshemmenden Arzneimitteln (z.B. Ketoprofen, Suprofen) entwickelt

Kinetics analysis and automated online screening of aminocarbonylation of aryl halides in flow

Temperature, pressure, gas stoichiometry, and residence time were varied to control the yield and product distribution of the palladium-catalyzed aminocarbonylation of aromatic bromides in both a silicon microreactor and a packed-bed tubular reactor. Automation of the system set points and product sampling enabled facile and repeatable reaction analysis with minimal operator supervision. It was observed that the reaction was divided into two temperature regimes. An automated system was used to screen steady-state conditions for offline analysis by gas chromatography to fit a reaction rate model. Additionally, a transient temperature ramp method utilizing online infrared analysis was used, leading to more rapid determination of the reaction activation energy of the lower temperature regimes. The entire reaction spanning both regimes was modeled in good agreement with the experimental data

Synthesis of 4H-Benzo[e][1,3]oxazin-4-ones by a Carbonylation–Cyclization Domino Reaction of ortho-Halophenols and Cyanamide

A mild and convenient one-step preparation of 4H-1,3-benzoxazin-4-ones by a domino carbonylation–cyclization process is developed. Readily available ortho-iodophenols are subjected to palladium-catalyzed carbonylative coupling with Mo(CO)6 and cyanamide, followed by a spontaneous, intramolecular cyclization to afford 4H-1,3-benzoxazin-4-ones in moderate to excellent yields. Furthermore, the scope of the reaction is extended to include challenging ortho-bromophenols. Finally, to highlight the versatility of the developed method, Mo(CO)6 is successfully replaced with a wide array of CO-releasing reagents, such as oxalyl chloride, phenyl formate, 9-methylfluorene-9-carbonyl chloride, and formic acid, making this an appealing strategy for the synthesis of 4H-benzo[e][1,3]oxazin-4-ones

Carbonylation of Anthranilic Acid with Aryl and Heteroaryl Bromides to Synthesize Benzoxazinone Derivatives

A simple and efficient, PdCl2(PhCN)2/P(tBu)3⋅HBF4‐catalyzed carbonylative cyclization of anthranilic acid with aryl bromide was investigated for the synthesis of benzoxazinones under mild reaction conditions. The developed protocol has been extended for the synthesis of quinazolin‐4(3 H)‐ones. Furthermore, the tolerance of a wide range of functional groups on anthranilic acid as well as on aryl bromide demonstrates the practical utility of the protocol.Three in 1: A simple and efficient PdCl2(PhCN)2/P(tBu)3⋅HBF4‐catalyzed carbonylative cyclization of anthranilic acid with aryl bromide was investigated for the synthesis of benzoxazinones under mild reaction conditions.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137223/1/ajoc201600253.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137223/2/ajoc201600253-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137223/3/ajoc201600253_am.pd

Mild Pd-Catalyzed Aminocarbonylation of (Hetero)Aryl Bromides with a Palladacycle Precatalyst

A palladacyclic precatalyst is employed to cleanly generate a highly active XantPhos-ligated Pd-catalyst. Its use in low temperature aminocarbonylations of (hetero)aryl bromides provides access to a range of challenging products in good to excellent yields with low catalyst loading and only a slight excess of CO. Some products are unattainable by traditional carbonylative coupling.National Institutes of Health (U.S.) (Award GM46059)Danish National Research Foundation (Grant DNRF59)Villum FoundationDanish Council for Independent Researc

Gutachter:

Doctor rerum naturalium (Dr. rer. nat.