Chromium- and Cobalt-Catalyzed Cross-Coupling and Amination Reactions and Synthesis and

172 Pages·2016·5.69 MB·English

by  Sarah Fernandez

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

CHROMIUM- AND COBALT-CATALYZED
CROSS-COUPLING AND AMINATION REACTIONS

AND
SYNTHESIS AND REACTIVITY OF
PYRIDO[3,2-F][1,7]NAPHTHYRIDINES

VON

SARAH FERNANDEZ

AUS LAGNY-SUR-MARNE, FRANKREICH

2016
Erklärung

Diese Dissertation wurde im Sinne von §7 der Promotionsordnung vom 14. Februar 2013 von Herrn
Professor Dr. Paul Knochel betreut.

Eidesstattliche Versicherung

Diese Dissertation wurde eigenständig und ohne unerlaubte Hilfe bearbeitet.

München, 14. April 2016

…….…………………………….......
Sarah Fernandez

Dissertation eingereicht am: 14. April 2016
1. Gutachter: Prof. Dr. Paul Knochel
2. Gutachter: Prof. Dr. Konstantin Karaghiosoff

Mündliche Prüfung am: 13. Mai 2016
This work was carried out from February 2013 to March 2016 under the guidance of Prof. Dr. Paul Knochel
at the Department of Chemistry at the Ludwig-Maximilians-Universität Munich.
First, I would like to express my appreciation to Prof. Dr. Paul Knochel for giving me the great opportunity to
carry out my PhD thesis in his group, for his guidance and support in the course of my scientific research.
I am also very grateful to Prof. Dr. Konstantin Karaghiosoff for agreeing to be second reviewer of this thesis
and I thank all members of my defense committee – Prof. Dr. Manfred Heuschmann, Prof. Dr. Hendrik
Zipse, Prof. Dr. Klaus T. Wanner and Prof. Dr. Heinz Langhals – for their interest shown in this manuscript by
accepting to be referees.
Christoph Sämann, Dorian Didier and Alicia Castelló Micó, thanks to all of you for having meticulously
proofread this manuscript, your help have been priceless. Once again I could count on you.
I would like to extend my gratitude to all my past and present colleagues, in particular to those who shared
most good and bad moments with me, from hilarity to frustration, from dawn till dusk until success.
Without you all, it wouldn’t have been the same, and I will never forget that. Take care of you, and never
give up following your dreams. That’s the only road you really need to track.
Moreover, I would like to thank warmly all the members of the F2.012 lab: Dr. Christoph Sämann, Dr.
Olesya Kuzmina, Diana Haas, Johannes Nickel, Dr. Dorian Didier, Dr. Maitane Fernández, Susanne Bähr,
Willy Boudot, Alicia Castelló Micó, Johanna Frey, Céline Dorval, Alexander John, Moritz Balkenhohl and
Maximilian Hofmayer. Thanks for making our lab the coolest! Between the greatest music hits – Jon Lajoie
will ever remain the lab hymn –, the oddest conversations about chemistry and life, without forgetting the
hilarious after-work moments, we’ve definitively been the greatest lab ever… Thanks also for having tried –
and proved – to be as crazy as me: Maita, DD, Ali and Momo (BSc), you really made me feel myself.
My next thought will definitively be turned to my coworkers: Olesya Kuzmina, Andi Steib, whom I warmly
thank for having taken me on the road of their “Pd-substitute search” road. I was glad to be part of the
fruitful “catalysis subgroup”. I would also like to show my appreciation to my Japanese colleague, Yuji
Niishi. Finally, I can’t forget those that helped me bring my azaphenanthrene topic till maturity: Maximilian
Ganiek, Maria Karpacheva, Florian Auras, without forgetting my Italian sister Dr. Chiara Marelli.
My gratitude goes also to the students I had the pleasure to supervise: Willy, Susi, Adrian and Johanna.
Thank you for having invested your time and energy in my projects, and for having shared ideas, hope and
deceptions with me.
I would also like to thank Dr. Vladimir Malakhov, Renate Schröder, Sophie Hansen, Yulia Tsvik, and of course
Peter James Dowling, for their help in organizing everyday life in the lab, as well as the analytical team of
the LMU for their invaluable help.
Besides, I won’t forget my best friends from France, Germany and abroad: Sarah, Audrey, Marie, François,
Fred, Dorian, Eléa and Alicia. Thanks for sharing both sadness and happiness, for always being there for me
no matter what, for pushing and reassuring me. Simply thank you to be you.
Merci Maman et Papa pour m’avoir laissé libre de mes choix et m’avoir permis d’arriver jusqu’ici. Tatie et
Mamie, sans votre soutien, je ne serais jamais allée aussi loin. A jamais dans mon coeur, Max et Zach, mes
petits frères, j’espère vous avoir prouvé qu’entre travail et volonté, on finit par atteindre ses rêves. Je vous
aime tous très fort.
Finally, my last thought will be for Christoph, the greatest person I’ve ever met. Thank you for existing, and
for the happy coincidence that life made you love me. Without you believing in me as you always do, I
would never have made it.
PARTS OF THIS PHD THESIS HAVE BEEN PUBLISHED

Communications and full papers:

1. S. Fernandez, M. A. Ganiek, M. Karpacheva, F. Auras, T. Bein, P. Knochel, “Synthesis
and Reactivity of new Triazaphenanthrenes”, manuscript in preparation.

2. O. M. Kuzmina, A. K. Steib, S. Fernandez, W. Boudot, J. T. Markiewicz, P. Knochel,
“Practical Iron- and Cobalt-Catalyzed Cross-Coupling Reactions between N-Heterocyclic
Halides and Aryl or Heteroaryl Magnesium Reagents“, Chem. Eur. J. 2015, 21, 8242.

3. A. K. Steib, S. Fernandez, O. M. Kuzmina, M. Corpet, C. Gosmini, P. Knochel,
“Chromium(II)-Catalyzed Amination of N-Heterocyclic Chlorides with Magnesium
Amides”, Synlett 2015, 26, 1049.

4. A. K. Steib, O. M. Kuzmina, S. Fernandez, S. Malhotra, P. Knochel, “Chemoselective
Chromium(II)-Catalyzed Cross-Coupling Reactions of Dichlorinated Heteroaromatics
with Functionalized Aryl Grignard Reagents”, Chem. Eur. J. 2015, 21, 1961.

5. A. K. Steib, O. M. Kuzmina, S. Fernandez, D. Flubacher, P. Knochel, “Efficient
Chromium(II)-Catalyzed Cross-Coupling Reactions between Csp2 Centers”, J. Am. Chem.
Soc. 2013, 135, 15346.

Review:

S. Fernandez, A. K. Steib, O. M. Kuzmina, P. Knochel, “Iron-, Cobalt- and Chromium-
Catalyzed Cross-Coupling Reactions », Actual. Chim. 2015, 393-394, 62.

A mes frères,
Maxime et Zachary,
votre Amie pour la Vie.
To Christoph,
For everything he is, and everything he will be.

“Un oiseau sur un arbre n’a jamais peur que la branche casse.
Sa confiance n’est pas dans la branche,
mais dans ses propres Ailes.”

- Anonymous -
TABLE OF CONTENTS
A. INTRODUCTION 1
1. OVERVIEW 2
2. PALLADIUM- AND NICKEL-CATALYZED CROSS-COUPLING AND AMINATION REACTIONS 3
2.1 PALLADIUM- AND NICKEL-CATALYZED CROSS-COUPLING REACTIONS 3
2.2 PALLADIUM-CATALYZED AMINATION REACTIONS 5
3. IRON-CATALYZED CROSS-COUPLING AND AMINATION REACTIONS OF AROMATICS AND
HETEROAROMATICS 10
3.1 IRON-CATALYZED CROSS-COUPLING REACTIONS OF AROMATIC AND HETEROAROMATIC
ELECTROPHILES 10
3.2 IRON-CATALYZED AMINATION REACTIONS OF (HETERO)AROMATIC ELECTROPHILES WITH
NITROGEN-NUCLEOPHILES 17
4. COBALT-CATALYZED CROSS-COUPLING AND AMINATION REACTIONS OF AROMATICS AND
HETEROAROMATICS 22
4.1 COBALT-CATALYZED CROSS-COUPLING REACTIONS OF AROMATIC AND HETEROAROMATIC
ELECTROPHILES 22
4.2 COBALT-CATALYZED AMINATION REACTIONS OF (HETERO)AROMATIC ELECTROPHILES WITH
NITROGEN-NUCLEOPHILES 26
5. CHROMIUM-CATALYZED TRANSFORMATIONS 30
6. SYNTHESIS OF PYRIDONAPHTHYRIDINES 34
7. OBJECTIVES 37
B. RESULTS AND DISCUSSION 40
1. COBALT(II)-CATALYZED CROSS-COUPLING REACTIONS BETWEEN N-HETEROCYCLIC HALIDES AND
ARYL OR HETEROARYL MAGNESIUM REAGENTS 41
1.1 COBALT-CATALYZED CROSS-COUPLING REACTIONS UTILIZING ISOQUINOLINE AS LIGAND 41
1.2 LIGAND SCREENING FOR THE COBALT-CATALYZED CROSS-COUPLING OF CHLOROPYRIDINES 44
2. CHROMIUM(II)-CATALYZED CROSS-COUPLING REACTIONS BETWEEN CSP2 CENTERS 51
2.1 PRELIMINARY EXPERIMENTS 51
2.2 CROSS-COUPLING REACTIONS OF 2-HALOGENATED N-HETEROCYCLES WITH ARYL GRIGNARD
REAGENTS 52
2.3 CROSS-COUPLING REACTIONS OF 2-HALOGENATED (HETERO)ARYL SUBSTITUTED KETONES WITH
(HETERO)ARYL GRIGNARD REAGENTS 54
2.4 CROSS-COUPLINGS BETWEEN IMINE-PROTECTED ALDEHYDES AND ORGANOMAGNESIUM REAGENTS 55
2.5 CROSS-COUPLING REACTIONS OF ALKENYL IODIDES WITH ARYL GRIGNARD REAGENTS 56
2.6 CHEMO- AND REGIOSELECTIVE CROSS-COUPLING REACTIONS OF DICHLORINATED
HETEROAROMATICS 56
2.7 REMOVAL OF THE CHROMIUM CATALYST 63
I