Synthesis and application of chiral phosphorous triamide ligands [Elektronische Ressource] / vorgelegt von Katalin Barta

Informations

• Publié par: rheinisch-westfalischen_technischen_hochschule_-rwth-_aachen
• Publié le: 01 janvier 2008
• Nombre de lectures: 9
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Synthesis and application of chiral phosphorous triamide ligands



Von der Fakultät für Mathematik, Informatik und Naturwissenschaften der RWTH Aachen
University zur Erlangung des akademischen Grades einer Doktorin der Naturwissenschaften
genehmigte Dissertation


vorgelegt von

MsSc. Katalin Barta
aus Bratislava, Slowakei




Berichter: Universitätsprofessor Dr. Walter Leitner
Universitätsprofessor Dr. István Tamás Horváth
Tag der mündlichen Prüfung: 24.07.2008





Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online verfügbar
1 dedicated to Zoltán






















„You cannot hope to build a better world without improving the individuals. To that end each
of us must work for his own improvement, and at the same time share a general responsibility
for all humanity, our particular duty being to aid those to whom we think we can be most
useful.“ Marie Curie
2 Der experimentelle Teil der vorliegenden Arbeit wurde in der Zeit von September 2003 bis
März 2008 am Institut für Technische und Makromolekulere Chemie der Rheinische-
Westfälischen Technischen Hochschule Aachen unter Anleitung von Univ.-Prof.Dr.Walter
Leitner angefertigt.
3 Abstract (English)

In this thesis the synthesis and application of novel chiral monodentate phosphorous
triamide (PTA) ligands is presented.
First, a small library of chiral PTAs based on three different chiral diamine backbones has
been prepared through a convenient modular synthetic approach. The study significantly
increases the knowledge about the synthesis, purification, stability and structural features
of these compounds. The prepared ligand library was evaluated in the asymmetric
hydrogenation as well as in two different asymmetric C-C bond forming reactions. All
tested structurally very different PTAs show poor performance in the Rh catalysed
hydrogenation of dimethyl itaconate. In contrast, better results could be obtained in the Cu
catalysed Michael-addition of diethyl zink to cyclohexenone where enantioselectivity
values up to 60 % have been achieved. Good conversions, selectivities and promising
enantioselectivity of 63 % was attained in the Ni catalysed hydrovinylation of styrene at
relatively high reaction temperature.
The results of this thesis demonstrate that chiral PTAs are accessible and can provide
significant levels of enantioselectivity in asymmetric catalysis. Their steric and electronic
properties can be fine-tuned by the variation of the amine components.
In general, the behaviour of these ligands is significantly different from the related
phosphites or phosphoramidites and their potential in enantioselective catalysis is not yet
fully explored.
4 Abstract (German)

Diese Doktorarbeit befasst sich mit der Synthese und Anwendung von neuartigen chiralen
Phosphor(III)triamiden (PTA).
Zunächst wurde eine kleine Bibliothek chiraler PTA basierend auf drei verschiedenen
chiralen Diamineinheiten über eine modulare Syntheseroute entwickelt. Die Ergebnisse
bieten Einsicht in die Synthese und Reinigung sowie die Stabilität und Struktur dieser
neuen Verbindungen. Die erhaltene Ligandenbibliothek wurde in der asymmetrischen
Hydrierung sowie in zwei asymmetrischen C-C Knüpfungsreaktionen getestet. Alle
getesteten Liganden haben sich in der Rhodium-katalysierten asymmetrischen Hydrierung
von Dimethylitakonat als nicht geeignet erwiesen. Gute Ergebnisse wurden in der Kupfer-
katalysierten Michael-Addition von Diethylzink an Cyklohexenon erhalten:
Enantioselektivitäten von bis zu 60 % wurden erreicht. Hohe Umsätze, gute Selektivitäten
und ein Enantiomerenüberschuss von 63 % wurden in der Nickel-katalysierten
Hydrovinylierung von Styrol bei relativ hoher Reaktionstemperatur erzielt.
Allgemein verhielten sich die dargestellten Liganden sehr unterschiedlich im Gegensatz
zu verwendeten Phosphiten und Phosphoramiditen. Die Ergebnisse der vorliegenden
Arbeit zeigen den Zugang zu chiralen PTA, und dass mit ihnen beachtliche
Enantioselektivitäten in der asymmetrischen Katalyse erreicht werden konnten. Die
sterischen und elektronischen Eigenschaften der PTA können weitgehend über die Wahl
der Aminkomponenten eingestellt werden. Das volle Anwendungspotential dieser neuen
Ligandenklasse ist noch lange nicht ausgeschöpft.
5 CONTENTS

1. Introduction
1.1 Background and motivation
1.2 Research objective

2. State of the art
2.1 Phosphorous triamides (PTAs)
2.1.1 Phosphoric acid derivatives: generalities
2.1.2 PTAs as synthetic intermediates and derivatising agent
2.1.3 Achiral PTAs: electonic features and coordination abilites
2.1.4 Proazaphosphatranes: structure and applications
2.1.5 Chiral PTAs: synthesis and applications in asymmetric catalysis
2.1.5.1 The first chiral PTA based on binaphthyl diamine framework
2.1.5.2 PTA library based on the bis(sulfonyl)diazaphospholidine moiety
2.1.5.3 P-chiral PTAs and their application in the allylic substitution
2.1.6. Summary

2.2. Rhodium catalysed asymmetric hydrogenation
2.2.1 General Aspects
2.2.2 Mechanism of the reaction

2.3 Copper catalysed Michael-addition of diethyl zink to enones
2.3.1 General Aspects
2.3.2 Mechanism of the reaction

2.4 Nickel catalysed asymmetric hydrovinylation
2.4.1 Ligand development
2.4.2 Mechanism of the reaction

3. Result and Discussion
3.1 Synthesis of novel chiral phosphorous triamide ligands
3.1.1 Synthetic strategies
3.1.2 General considerations concerning the synthesis of PTAs
6 3.1.3 Synthesis of PTA based on 1,2-diamino binaphthyl backbone
3.1.3.1 Theorethical aspects of structure and stablity
3.1.3.2 Synthesis of 1,2-binaphthyl-diamine based PTA
3.1.3.3 NMR spectroscopic study of L1 in solution
3.1.3.4 X-ray crystal structure of L1 in the solid state
3.1.4 Modular synthesis of PTA based on the 1,2-cyclohexyl-diamine moiety
3.1.4.1 Ligand synthesis via Route B
3.1.4.2 Modular synthesis via Route A
3.1.4.3 Coordination studies
3.1.4.4 Crystal structure analysis of L4
3.1.4.5 Crystal structure analysis of L9
3.1.5 Modular synthesis of (S)-N-phenyl-2-aminomethyl-pyrrolidine based PTA
3.1.5.1 Ligand synthesis via Route B
3.1.5.2 Separation of the diastereomers via borane complex
3.1.5.3 Crystal structure analysis of L13a. BH 3
3.1.5.4 Separation of the diastereomers via rhodium complex formation
3.1.5.5 Ligand synthesis via Route B as a method for the determination of the optical
purity of diamines
3.1.5.6. Ligand synthesis via Route A
3.1.5.7 Epimerisation of the diamino-phosphorous chloride 31
3.1.5.8 Modular ligand synthesis
3.1.5.9 Crystal structure analysis of ligands L18 and L20

3.2 Asymmetric catalysis with novel chiral PTAs
3.2.1 Asymmetric hydrogenation
3.2.2 Copper catalysed Michael addition
3.2.2.1 Binaphthyl diamine based PTA
3.2.2.2 Cyclohexyl diamine based PTA
3.2.2.3 (S)-N-phenyl-2-aminomethyl-pyrrolidine based PTA
3.2.3 Asymmetric hydrovinylation of styrene

4. Conculsions and outlook

5. Experimental
7 5.1 General methods, solvents and reagents
5.1.1 Inert Gas Conditions
5.1.2 Solvents
5.1.3 Reagents
5.1.4 Further purification of reagents
5.1.5 Thin Layer Chromatography
5.1.6 Column Chromatography and filtration
5.1.7 NMR spectroscopy
5.1.8 IR spectroscopy
5.1.9 Mass Spectroscopy

5.2 Chemicals prepared according to literature procedures

5.3 Syntheses
5.3.1 Precursor synthesis
5.3.2 Ligand synthesis
5.3.3 Borane adducts and metal complexes

5.5.4. Catalysis
5.5.4.1 Copper catalysed Michael addition
5.5.4.2 Hydrovinylation
5.5.4.3 Hydrogenation

6. Literature
7. Appendices
8. Acknowledgement
8 1. Introduction

1.1 Background and motivation
The need for enantiomerically pure compounds tremendously raised in the last decades. There
are numerous examples in medicinal applications where the two enantiomers of a chiral
1 2molecule have dramatically different effects. Nowadays, the principle of “racemic switches”
plays an important role in the commercialisation of drugs consisting exclusively of single
enantiomers and has a profound influence on the further development of fine chemical and
drug manufacturing.Enatiomerically pure compounds can be obtained by derivatisation of
3
substances coming from the chiral pool. This approach has the limitation that often only one
enantiomer is accessible. Alternatively, pure enantiomers can be isolated through the
4 separation of a racemic mixture by crystallisation, chromatography, or kinetic resolution.
Although this strategy is frequently used in the industry, it leads only to a maximum