Master of Science
Blacquiere, Johanna M.
Catalytic acceptorless dehydrogenation (AD) is an atom economic route for synthesizing imines and enamines, which are common final or intermediary functionalities in various pharmaceutically relevant molecules and materials. Imines, for example, are present in a wide range of syntheses due to their versatility. Meanwhile, indole is the 9th most common nitrogen heterocycle in FDA approved drugs. For imine synthesis via AD, selectivity challenges remain. Reactions often afford a product mixture of imine, nitrile, and a secondary amine. Previously, we showed that the metal-ligand cooperative (MLC) catalyst [Ru(Cp)(PPh2NBn2)(MeCN)]PF6 showed improved selectivity over a non-MLC catalyst. Herein, a broader scope of activity and selectivity assessment for the AD of amines, for a range of [M(Cp)(PR2NR’2)(MeCN)]PF6 catalysts will be discussed. [Ru(Cp)(PR2NR’2)(MeCN)]PF6 catalysts were explored for the AD of indoline to indole, which revealed that the activity depended on both the R and R’ groups of the PR2NR’2 ligand. In addition, both ruthenium and iron catalyst derivatives were explored for the AD of benzylamine, which showed that the iron-centered catalyst was highly selective towards the imine product. Investigations into the mechanism will be discussed that reveal connections between catalyst structure and performance.
Summary for Lay Audience
This thesis investigates the use of various catalysts for a chemical transformation crucial to the synthesis of significant molecules, with applications spanning the pharmaceutical, agrochemical, and fine chemical industries. Catalysts are substances that speed up chemical reactions without getting used up in the process. The best catalyst works for a long time without breaking down and exhibits selectivity for one specific product. However, during the chemical transformation of interest, the reaction can often yield more than one product, even with the catalyst's intervention. In chemistry, molecules like imine, nitriles, and N-heterocycles stand out as significant players. Imines and nitriles, with their versatile nature, often act as middlemen in various chemical reactions to create more diverse compounds. Indoles, a nitrogen containing compound is the 9th most common structure found in FDA approved medications. Nonetheless, the process of synthesizing imines with the chemical transformation of interest has issues with selectivity to produce the desired product. In this work, A catalyst featuring an iron metal center emerged as uniquely selective, generating a single imine product. To better understand this phenomenon, an array of structurally distinct catalysts were tested, revealing clear correlations between structural attributes and catalytic performance. Adjustments to the catalysts' structures can enhance or change their efficacy. The iron catalyst’s role in the chemical transformation was confirmed via control reactions, which showed that without the catalyst, the reaction did not achieve the desired outcomes. The iron-based catalytic system presents a cost-effective alternative to traditional methods utilizing precious and costly metals such as ruthenium. Traditionally, ruthenium has been favored for these transformations due to its inherent ability to facilitate the chemical transformation of interest compared to other metals like iron. The implications of employing this iron-based catalyst are far-reaching marking a significant stride towards creating a more sustainable future.
Singh, Amrit, "Acceptorless Dehydrogenation of Amines using Metal Ligand Cooperative Catalysts" (2023). Electronic Thesis and Dissertation Repository. 9845.
Available for download on Friday, October 04, 2024