Oxidative Copper(I)-Mediated Cycloamination [Elektronische Ressource] : Preparation and Reactions of Heteroaromatic Benzylic Zinc Compounds ; Novel Preparation of Tertiary Benzylic and Phenethylic Amines / Andreas Johannes Wagner. Betreuer: Paul Knochel

Andreas Johannes Wagner

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2011
• Nombre de lectures: 16
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Dissertation zur Erlangung des Doktorgrades
der Fakultät für Chemie und Pharmazie
der Ludwig-Maximilians-Universität München





Oxidative Copper(I)-Mediated Cycloamination.
Preparation and Reactions of Heteroaromatic
Benzylic Zinc Compounds.
Novel Preparation of Tertiary Benzylic and Phenethylic Amines






von

Andreas Johannes Wagner


aus

Regensburg


2011
Erklärung

Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29.
Januar 1998 (in der Fassung der sechsten Änderungssatzung vom 16. August 2010) von
Professor Dr. Paul Knochel betreut.



Ehrenwörtliche Versicherung

Diese Dissertation wurde selbständig und ohne unerlaubte Hilfe bearbeitet.


München, 06. September 2011




…..……………………………………
Andreas J. Wagner






Dissertation eingereicht am: 06. September 2011

1. Gutachter: Prof. Dr. Paul Knochel
2. Gutachter: Prof. Dr. Manfred Heuschmann

Mündliche Prüfung am: 04. Oktober 2011

This work was carried out from February 2008 to August 2011 under the guidance of Prof. Dr.
Paul Knochel at the Department of Chemistry at the Ludwig-Maximilians-Universität Munich.



First of all, I thank Prof. Dr. Paul Knochel for his support and invaluable guidance in the course
of my scientific research.

I am also very grateful to Prof. Dr. Manfred Heuschmann for agreeing to be second reviewer of
this thesis and I thank all members of my defense committee – Prof. Dr. Thomas Carell, Prof. Dr.
Heinz Langhals, Prof. Dr. Konstantin Karaghiosoff and Prof. Dr. Rudolf Knorr for their interest
shown in this manuscript by accepting to be referees.

Christoph Sämann and Andreas Unsinn, who have been diligently proofreading this manuscript,
have been of invaluable help. Thank you, my friends.
I want to extend my gratitude to many past and present coworkers I have met in our research
group, in particular my good friends and lunch wingmen Dr. Fabian Piller, Dr. Christoph J.
Rohbogner, Andreas Unsinn and Sebastian Bernhardt. Many thanks to Klaus Groll, Veronika
Werner, Thomas Kunz, Tobias Blümke, Dr. Matthias Schade, Dr. Armin Stoll and Dr. Stefan
Wunderlich for a lot of great memories. F2.012 would not have been the same without my lab
mates, Andreas Steib, Prof. Dr. Giuliano C. Clososki, Dr. Elena Zaburdaeva and Dr. Nadège
Boudet. Thank you for everything we shared.

Special thanks to my hood neighbors Dr. Marcel Kienle and Dr. Cora Dunst for great symbiosis
and to Gabriel Monzón Díaz for the superb collaboration.

Je tiens à remercier cordialement mes étudiants en master Serge Ruccolo et Estelle Durantie qui
m’ont beaucoup aidé à progresser dans ma thèse.
I thank my longest-standing study colleagues and friends Mirjam Dogru and Dr. Tomke Bresser
for all the cool moments we have been sharing for almost a decade, in Großhadern, Tegernsee
and elsewhere.
Dr. Vladimir Malakhov deserves my special gratitude for his untiring support in my studies of the
Russian language and for our great trip to Moscow, and I want to thank Nadja Barl for being my
first and best linguistics student. Большое спасибо вам! Без вас, всё было бы очень скучнее.
Renate Schröder and Simon Matthe have been most helpful in organizing everyday life and I
wish them all the best for their future. Thank you!

Without the invaluable support - both moral and financial - I received from my parents, my
brother and my sister, I could not have done this. I am forever in your debt.

I hope to stay in touch with all of you. Whatever may become of us, let us not forget the good
times and laughs we had together!











Meinen Freunden
A mes amis
To my friends
Моим друзьям






































Ὁ βίος βραχύς,
ἡ δὲ τέχνη µακρή,
ὁ δὲ καιρὸς ὀξύς,
ἡ δὲ πεῖρα σφαλερή,
ἡ δὲ κρίσις χαλεπή.

- Ἱπποκράτης ὁ Κῷος -



Life is short,
art long,
opportunity fleeting,
experiment fallible,
judgment difficult.

- Hippocrates of Cos -

















Table of Contents
A. INTRODUCTION................................................................................................................................................... 3
1. OVERVIEW........................................................................................................................................................ 4
2. AMINATION REACTIONS ................................................................................................................................... 5
2.1. Transition-Metal Catalyzed Amination .................................................................................................. 6
2.2. Oxidative Amination Reaction................................................................................................................ 9
3. ORGANOZINC COMPOUNDS ............................................................................................................................ 10
3.1. Overview .............................................................................................................................................. 10
3.2. Preparations of Organozinc Compounds............................................................................................. 11
4. OBJECTIVES.................................................................................................................................................... 15
4.1. Oxidative Cu(I)-Mediated Cycloamination.......................................................................................... 15
4.2. Preparation and Reactions of Non-Conjugated Heteroaromatic Benzylic Zinc Compounds .............. 16
B. RESULTS AND DISCUSSION............................................................................................................................ 20
1. OXIDATIVE CU(I)-MEDIATED CYCLOAMINATION .......................................................................................... 21
1.1. Preparation of Precursors.................................................................................................................... 21
1.2. Oxidative Cycloamination.................................................................................................................... 28
2. PREPARATION AND REACTIONS OF NON-CONJUGATED HETEROAROMATIC BENZYLIC ZINC REAGENTS........ 32
2.1. Introduction.......................................................................................................................................... 32
2.2. Preparation of Heterobenzylic Amines ................................................................................................ 34
2.3. Preparation of Heterobenzylic Chlorides ............................................................................................ 39
2.4. Preparation and Reactions of Heterobenzylic Zinc Reagents.............................................................. 44
3. ONE-POT PREPARATION OF TERTIARY BENZYLIC AND PHENETHYLIC AMINES .............................................. 53
3.1. Overview .............................................................................................................................................. 53
3.2. Preparation of Tertiary Benzylic and Phenethylic Amines .................................................................. 55
3.3. Reactivity of Organozincs in the Presence of BF ·OEt ....................................................................... 58 3 2
4. SUMMARY AND OUTLOOK.............................................................................................................................. 62
4.1. Cu(I)-Mediated Oxidative Cycloamination.......................................................................................... 62
4.2. Preparation and Reactions of Non-Conjugated Heteroaromatic Benzylic Zinc Reagents................... 63
4.3. One-Pot Preparation of Tertiary Aromatic and Heteroaromatic Benzylic and Phenethylic Amines... 64
C. EXPERIMENTAL SECTION ............................................................................................................................. 65
1. GENERAL CONSIDERATIONS ................................................................................................................... 66
1.1. Solvents ................................................................................................................................................ 66
1.2. Reagents .........................................................................................................................