Regioselective functionalization of aromatics and heterocycles bearing a bis-silyl-methyl group

137 Pages·2015·1.46 MB·English

by  Veronika Werner

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

REGIOSELECTIVE FUNCTIONALIZATION OF AROMATICS AND
HETEROCYCLES BEARING A BIS-SILYL-METHYL GROUP,
ONE-POT PROCEDURE FOR THE PREPARATION OF TERTIARY AMINES
VIA IMINIUM IONS
AND PREPARATION OF NEW BENZODITHIOPHENE BUILDING BLOCKS
FOR COVALENT ORGANIC FRAMEWORKS

von

Veronika Werner

aus

München

2015
Erklärung
Diese Dissertation wurde im Sinne von § 7 der Promotionsordnung vom 28. November 2011
von Herrn Prof. Dr. Paul Knochel betreut.

Eidesstattliche Versicherung
Diese Dissertation wurde eigenständig und ohne unerlaubte Hilfe erarbeitet.

München, .....................................

.............................................................................
Veronika Werner

Dissertation eingereicht am: 29.01.2015
1. Gutachter: Prof. Dr. Paul Knochel
2. Gutachter: Prof. Dr. Thomas Bein
Mündliche Prüfung am: 24.02.2015

This work was carried out from March 2011 to February 2015 under the guidance of Prof. Dr. Paul
Knochel at the Department of Chemistry of the Ludwig-Maximilians-Universität Munich.
First of all, I thank Prof. Dr. Paul Knochel for giving me the opportunity to carry out my PhD in his
group and for his guidance and support in the course of my scientific research.
I would like to express my appreciation to Prof. Dr. Thomas Bein for agreeing to be second reviewer
of this thesis and I thank all members of my defense committee – Prof. Dr. Manfred Heuschmann,
Prof. Dr. Franz Bracher, Dr. Thomas Magauer and Prof. Dr. Herbert Mayr for their interest shown in
this manuscript by accepting to be referees.
I really would like to thank Christian Petermayer, Julia Nafe, Thomas Klatt and Lydia Klier for
carefully proofreading this manuscript.
I also thank Stephanie Linke, Matthias Becker, Fernando Rabasa Alcaniz and Christian Petermayer for
their contributions to my research during their internships.
Furthermore, I want to thank all past and present coworkers I have met in the Knochel group. I really
had a great time with you in the last four years. Special thanks to Dr. Thomas Kunz, Dr. Andreas
Wagner, Dr. Tobias Blümke, Dr. Matthias Schade, Dr. Silvia Zimdars, Dr. Klaus Groll, Julia Nafe, Dr.
Gabriel Monzon, Dr. Christoph Sämann and Dr. Andreas Unsinn. I’m deeply grateful for your
ongoing help, for motivating me anytime, all the nice moments we had in and outside the lab and for
your friendship! In this context, I’m deeply indebted to my “soulmate” Dr. Nadja Barl, who had
always a friendly ear for my thoughts and problems and helped me trough the most frustrating time of
my PhD.
I thank all the great past and present chemists of F2.004, Dr. Silvia Zimdars, Dr. Thomas Kunz, Zhi-
Liang Shen, Dr. Christos Stathakis, Dr. Xavier Mollat du Jourdin and Dr. Sebastian Bernhardt. Special
thanks to Pauline Quinio for all the music we shared in the last two years. All of you created an
excellent working and sometimes party atmosphere and have been the best labmates one could
imagine.
I want to thank Thomas Klatt, for his permanent help and our strong collaboration on the BTSM-topic
and Mario Ellwart for our short but quite productive collaboration on the Iminium-project. I thank all
the present and former members of the Material-team for fruitful discussions and a strong
collaboration: Dr. Mirjam Dogru, Dr. Dana Medina, Dr. Thomas Kunz, Dr. Silvia Zimdars, Dr. John
Markiewicz and Julia Nafe.
Furthermore, I thank my dearest friends for the great time we had during our studies in the last nine(!)
years. My heartfelt thanks to my “Topmodel Spassten“, Katl and Chris, as well as to my
“Stammtisch“, Gina, Floh and Netti. In this context, I also thank Simon and Tanja.
A big thank-you to Vladi “Waldimir” Malakhov, Renate Schröder, Peter Dowling, Sophie Hansen
and Yulia Tsvik for being indispensable in organizing everyday life in the lab and the office.
Zum Schluss danke ich meiner Familie für eure unermüdliche Hilfe, Unterstützung und Liebe, die ich
in den letzten Jahren erhalten habe, ohne euch wäre ich jetzt nicht hier. Mein großer Dank geht an
dieser Stelle auch an Chris: Danke, dass du mir immer wieder den Rücken gestärkt hast, mich
aufbauen konntest und die letzten Monate meines PhDs zu einigen der schönsten hast werden lassen.

Parts of this Ph.D. Thesis have been published:
Publications:
Dana. D. Medina, Veronika Werner, Florian Auras, Raphael Tautz, Mirjam Dogru, Jörg Schuster,
Stephanie Linke, Markus Döblinger, Jochen Feldmann, Paul Knochel, Thomas Bein: ”Oriented Thin
Films of a Benzodithiophene Covalent Organic Framework”, ACS Nano 2014, 8(4), 4042-4052.

Veronika Werner, Thomas Klatt, Masaya Fujii, Jenifer Markiewicz, Yitzhak Apeloig, Paul Knochel:
“Preparation and Regioselective Metalation of Bis(trimethylsilyl)methyl-Substituted Aryl
Derivatives”, Chem. Eur. J. 2014, 20(27), 8338-8342.

Dana D. Medina, Julian Rotter, Yinghong Hu, Mirjam Dogru, Veronika Werner, Florian Auras, John
Markiewicz, Paul Knochel, Thomas Bein: “Room Temperature Synthesis of Covalent Organic
Framework Films through Vapor Assisted Conversion”, J. Am. Chem. Soc. 2015, accepted for
publication.

Veronika Werner, Mario Ellwart, Andreas J. Wagner, Paul Knochel: “Preparation of Tertiary Amines
by the Reaction of Iminium Ions Derived from Unsymmetrical Aminals with Zinc and Magnesium
Organometallics”, manuscript submitted.

Thomas Klatt, Veronika Werner, Marina G. Maximova, D. Didier, Yitzhak Apeloig, Paul Knochel:
“Preparation and Regioselective Magnesiation or Lithiation of Bis(trimethylsilyl)methyl-Substituted
Heteroaryls for the Generation of Highly Functionalized Heterocycles”, manuscript submitted.

Review Articles:
Nadja M. Barl, Veronika Werner, Christoph Sämann, Paul Knochel: “The Halogen/Magnesium-
Exchange Using iPrMgCl·LiCl and Related Exchange Reagents”, Heterocycles 2014, 88(2), 827-844.
M F
EINER AMILIE
“Wissenschaft:
Es ist nicht ihr Ziel, der unendlichen Weisheit eine Tür zu öffnen,
sondern eine Grenze zu setzen dem unendlichen Irrtum”
BERTOLD BRECHT
(1898 - 1956)
Table of Contents
A: INTRODUCTION ....................................................................................................................... 5
1. OVERVIEW ........................................................................................................................... 6
2. REGIOSELECTIVE METALATION OF BTSM-FUNCTIONALIZED AROMATICS ............................ 7
2.1. Directed ortho-Metalation ................................................................................................................... 7
2.2. The BTSM-Group ................................................................................................................................. 8
2.3. Objectives .......................................................................................................................................... 10
3. GENERATION OF TERTIARY AMINES VIA IMINIUM IONS ..................................................... 12
3.1. The Mannich Reaction ....................................................................................................................... 12
3.2. Iminium salts ..................................................................................................................................... 13
3.3. Phenethylamines ............................................................................................................................... 15
3.4. Objectives .......................................................................................................................................... 17
4. NEW BUILDING BLOCKS FOR COVALENT ORGANIC FRAMEWORKS .................................... 18
4.1. Porous Materials ............................................................................................................................... 18
4.2. Covalent Organic Frameworks ........................................................................................................... 18
4.3. Objectives .......................................................................................................................................... 20
B: RESULTS AND DISCUSSION .................................................................................................... 22
1. REGIOSELECTIVE FUNCTIONALIZATION OF AROMATICS AND HETEROCYCLES BEARING A
BULKY BIS-SILYL-METHYL GROUP .............................................................................................. 23
1.1. Introduction....................................................................................................................................... 23
1.2. Preparation of BTSM-Substituted Aromatics ..................................................................................... 23
1.3. Regioselective Functionalization of BTSM-Substituted Derivatives .................................................... 26
1.4. Transformation of the BTSM-Group................................................................................................... 32
1.5. Preparation of BTSM-Substituted Heteroaromatics ........................................................................... 33
1.6. Regioselective Functionalization of the Thiophene Scaffold .............................................................. 34
2. ONE-POT PROCEDURE FOR THE PREPARATION OF TERTIARY AMINES VIA IMINIUM IONS . 41
2.1. Introduction....................................................................................................................................... 41
2.2. One-Pot Procedure for the Preparation of Tertiary Amines ............................................................... 43
2.3. One-Pot Preparation of Tertiary Amines by Using Various Zinc Reagents .......................................... 44
2.4. One-Pot Preparation of Tertiary Amines by Using Grignard Reagents ............................................... 48
3. PREPARATION OF NEW BENZODITHIOPHENE BUILDING BLOCKS FOR COVALENT ORGANIC
FRAMEWORKS ........................................................................................................................... 50
3.1. Introduction....................................................................................................................................... 50
3.2. Preparation of the BDT Scaffolds ....................................................................................................... 50
3.3. Preparation of the BDT-Linker ........................................................................................................... 52
3.4. Integration of the Diboronic Acid Linkers in Covalent Organic Frameworks ....................................... 53
4. SUMMARY .......................................................................................................................... 55
4.1. Regioselective Functionalization of Aromatics and Heterocycles Bearing a Bulky bis-Silyl-Methyl
Group…. ......................................................................................................................................................... 55
4.2. One-Pot Procedure for the Preparation of Tertiary Amines via Iminium Ions .................................... 58
4.3. Preparation of New Benzodithiophene Building Blocks for Covalent Organic Frameworks ................ 59
C: EXPERIMENTAL SECTION ....................................................................................................... 60
1. GENERAL CONSIDERATIONS ............................................................................................... 61
1.1. Solvents ............................................................................................................................................. 61