Highly enantioselective hydroamination to six-membered rings by heterobimetallic catalysts

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.New bimetallic Zn/Zr salen-type systems were employed as catalysts in the asymmetric intramolecular hydroamination reaction. High enantioselectivity for the formation of piperidines of up to 98% ee were observed.DFG, TRR 88, Kooperative Effekte in homo- und heterometallischen Komplexen (3MET

Heterobimetalle und Monometallische Katalysatoren für Asymmetrische Hydroaminierung und Tandem Reaction

Hydroaminierungsreaktionen gehören zu den am vielseitigst einsetzbaren Methoden um Stickstoffheterozyklen, welche in vielen chemischen Bereichen von großem Interesse sind, aufzubauen. Obwohl diese Art der Reaktion bereits intensiv erforscht wurde gibt es noch viele Herausforderungen. In dieser Arbeit wird die Entwicklung verschiedener chiraler und achiraler Zink-Katalysatoren beschrieben, deren Anwendung auf den Gebieten der inter- und intramolekularen Hydroaminierung von Alkenen und Alkinen untersucht wurde. Außerdem wurden Untersuchungen bezüglich des Mechanismus durchgeführt. Das erste Kapitel befasst sich mit der Wichtigkeit von Aminen und Methoden der Darstellung. Verschiedene Metall-Katalysatoren inklusive deren Stellung im Periodensystem, Vor- und Nachteile und Mechanismen bezüglich Hydroaminierungen werden vorgestellt und diskutiert. Außerdem wird erklärt, wieso Zink für diese Arbeit als Metall gewählt wurde. Im zweiten Kapitel werden Zink-katalysierte konsekutive oder Domino-Reaktionen zwischen Aminen und Alkinen beschrieben, welche 1,2-Dihydroquinolin-Derivate als Produkte liefern. Eine konsekutive Reaktionsführung erlaubt die Minimierung der Reaktionsschritte. Am Ende des Kapitels werden Resultate, Beobachtungen und ein möglicher Mechanismus vorgestellt. Im dritten Kapitel werden die Arbeiten bezüglich der asymmetrischen, intramolekularen Hydroaminierung präsentiert. Die Synthese des chiralen Liganden, sowie elektronische und sterische Modifikationen werden beschrieben. Die Liganden werden in enantioselektiven, intramolekularen Hydroaminierungen eingesetzt. Darüber hinaus wurden verschiedene Übergangsmetalle eingesetzt. Die Kombination von Zink und Zirkonium lieferte die besten Resultate. Am Ende des Kapitels werden die Ergebnisse von kinetischen und NMR-Studien diskutiert, mit deren Hilfe ein plausibler Mechanismus vorgestellt wird. Im vierten Kapitel wird die Entwicklung eines neuen und effizienten TMP-ZnCl-Katalysators und dessen Einsatz in der Hydroaminierung präsentiert. Mit dem TMP-ZnCl- Katalysator konnten mittels Hydroaminierung effektiv Pyrrolidinsysteme aus primären und sekundären Aminoalkenen sowieso Aminoaklinen dargestellt werden. In diesem Kapitel wird außerdem ein weiteres Projekt vorgestellt, welches den Einsatz von Dibutylmagnesium als effektiven Katalysator in der Hydroaminierung beschreibt. Dieser Katalysator erwies sich in unserer Arbeitsgruppe bereits als effizienter Katalysator in der Darstellung von Pyrrolidinsystemen. In dieser Arbeit wurde die Einsatzmöglichkeit bezüglich der Darstellung von Piperidinsystemen untersucht.The hydroamination reaction is among the most versatile means of forming nitrogen-containing heterocycles, compounds of interest in a variety of chemical disciplines. While the reaction has been intensely studied, concerns still exist over its amenability to organic synthesis. This thesis details the development of various zinc based chiral and achiral catalysts for inter and intramolecular hydroamination reactions of alkenes and alkynes and mechanistic studies. The first chapter consists of importance of the amines and the methods of preparation have been described. Different metal catalysts according to their position in periodic table which are been used for hydroamination, their advantages and disadvantages are been highlighted including the mechanism of the processes. Finally why zinc has been chosen as the most suitable metal for the hydroamination reaction has been explained. The second chapter contains a consecutive or domino hydroamination reaction between amine and alkyne to produce bicyclic and tricyclic- 1,2-dihydroquinoline derivatives catalysed by a zinc complex. This consecutive reaction gives us the possibility to diminish the number of step to obtain the resulted products. At the end of this chapter, the results and observations of this reaction prone us to propose a possible mechanism. In third chapter, intramolecular asymmetric hydroamination has been described. Starting from the chiral ligand synthesis and modification of electronic, steric factors on ligand has been described micro analytically. Then ligands are been used for enantioselective intramolecular hydroamination. Metal centre has also been varied by different transition and also late transition metals. The combination of zinc and zirconium shows the best results. At the end of the chapter, some kinetic study and NMR study has been carried out to understand the mechanism of the reaction and with the observed results the mechanism has been established. Forth chapter describes the development of new and very efficient catalyst TMP-ZnCl for hydroamination. Using this TMP-ZnCl as a catalyst, primary amino-alkene, secondary amino-alkene and also amino-alkynes showed hydroamination reaction to form pyrrolidine systems efficiently. This chapter also contains a separate project which involved the development of Di-butyl magnesium as an efficient catalyst for hydroamination. This catalyst has already shown to be an efficient catalyst for hydroamination to form pyrrolidine systems in our laboratory. Here we tested the efficiency of this catalyst for hydroamination to obtain piperidine derivatives

Regiospecific N-Arylation of Aliphatic Amines under Mild and Metal-Free Reaction Conditions

A transition metal-free N-arylation of primary and secondary amines with diaryliodonium salts is presented. Both acyclic and cyclic amines are well tolerated, providing a large set of N-alkyl anilines. The methodology is unprecedented among metal-free methods in terms of amine scope, the ability to transfer both electron-withdrawing and electron-donating aryl groups, and efficient use of resources, as excess substrate or reagents are not required

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

The arylation of heteroatom nucleophiles is a central strategy to reach diarylated compounds that are key building blocks in agrochemicals, materials and pharmaceuticals. Nucleophilic aromatic substitution is a classical tool for such arylations, and hypervalent iodine-mediated arylations are modern alternatives to achieve a wider scope of products. Herein, we combine the benefits of those strategies to enable an atom-efficient and transition metal-free functionalization of N- and O- nucleophiles with two structurally different aryl groups, to provide di- and triarylamines and diaryl ethers in one single step (> 100 examples). The core of this strategy is the unique reactivity discovered with certain fluorinated diaryliodonium salts, which unveils novel reaction pathways in hypervalent iodine chemistry. The method is suitable for aliphatic amines, anilines, ammonia and even water and tolerates a wide variety of functional and protecting groups. Furthermore, the retained iodine substituent is easily accessible for derivatization of the products

Ligand-free copper-catalyzed synthesis of substituted benzimidazoles, 2-aminobenzimidazoles, 2-aminobenzothiazoles, and benzoxazoles

The synthesis of substituted benzimidazoles, 2-aminobenzimidazoles, 2-aminobenzothiazoles, and benzoxazoles is described via intramolecular cyclization of o-bromoaryl derivatives using copper(II) oxide nanoparticles in DMSO under air. The procedure is experimentally simple, general, efficient, and free from addition of external chelating ligands. It is a heterogeneous process and the copper(II) oxide nanoparticles can be recovered and recycled without loss of activity

Hypervalent Iodine Mediated Oxidative Amination of Allenes

An oxidative amination of allenes using a single hypervalent iodine reagent is reported. The reaction proceeds very efficiently for monosubstituted allenes and leads to formation of the corresponding propargylic amines, either as the internal or as the terminal amine. The respective reaction outcome could be influenced in favor of the former product by addition of triphenylphosphine oxide to the iodine­(III) reagent