Multicomponent heterocycle syntheses based upon Sonogashira coupling-isomerization [Elektronische Ressource] / vorgelegt von Oana G. Schramm

B Ghaleb

Informations

• Publié par: ruprecht-karls-universitat_heidelberg
• Publié le: 01 janvier 2006
• Nombre de lectures: 24
• Langue: English
• Poids de l'ouvrage: 3 Mo

Extrait

INAUGURAL - DISSERTATION







zur
Erlangung der Doktorwürde
Der Naturwissenschaftlich-Mathematischen-gesamtfakultät
der
Ruprecht-Karls-Universität
Heidelberg






vorgelegt von
M. Sc. Oana G. Schramm
Aus Barlad, Rumänien



Tag der Disputation:
21.07.06










Multi-component Heterocycle Syntheses Based upon
Sonogashira Coupling-Isomerization









Gutachter: Prof. Dr. Thomas J. J. Müller
Prof. Dr. Sven Doye
























Hiermit erkläre ich an Eides statt, dass ich die vorliegende Arbeit selbständig und ohne
unerlaubte Hilfsmittel durchgeführt habe.




Heidelberg, im Mai 2006



Acknowledgements

First and foremost, I would like to thank my advisor, Prof. Dr. Thomas J. J. Müller, for his
excellent guidance, patience and continuous support. Throughout my doctoral work he
encouraged me to develop independent thinking and research skills.

I am very grateful to Mrs. Dr. Christa Krämer, Mr. Dr. Alexei Karpov, and Mr. Dr. Alexandru
Rotaru for helpful discussions and valuable advices.

I am truly thankful to Mrs. Karin Memminger, Mrs. Nadine Körber, and Mr. Benjamin Willy
for their useful suggestions and comments during the preparation of this manuscript.

I extend many thanks to all my colleagues for their support and special working atmosphere.

I also thank to Mrs. Anette Loos and Mrs. Birgit Thaler for their efforts during the research
practice.

I am indebted to Mrs. Tanja Coelho, Mrs. Margaret Fischer, Mr. David Haseloff, Mr. Dr.
Julien Furrer and Mr. Dr. Schilling for NMR spectra, Mrs. Petra Krämer for UV/Vis and IR
spectra, Mrs. Bianka Flock, Mrs. Angelika Seith, Mr. Norbert Nieth, and Mr. Dr. Jürgen
Gross for mass spectra, Mrs. Vetter, and Mr. Liebscher for carrying out of elemental analyses,
Mr. Dr. Thomas Oeser and Mr. Dr. Romminger for supplying with X-Ray structures.

I am deeply grateful to my parents Florica and Ioan Dediu, and my brother Ionut Dediu who
have always encouraged and supported me.

I would like also to thank my husband, Berthold, for being by my side and encouraging me
during my Ph.D. work.

Last, but far from least, I would like to thank all my friends for their kind support.



Parts of this thesis have already been published or submitted for publication:


Publications

1. “The Coupling-Isomerization Approach to Enimines and the First Sequential Three-
Component Access to 2-Ethoxy Pyridines”, Oana G. Dediu, Nasser A. M. Yehia, and
Thomas J. J. Müller, Z. Naturforsch. 2004, 59b, 443–450.

2. “Coupling-Isomerization-Enamine Addition-Cyclocondensation Sequences: A
Multicomponent Approach to Substituted and Annelated Pyridines”, Oana G. Dediu,
Nasser A. M. Yehia, Thomas Oeser, Kurt Polborn, and Thomas J. J. Müller, Eur. J. Org.
Chem. 2005, 1834−1848.

3. “Coupling-Isomerization-N,S-Ketene Acetal-Addition Sequences – A Three-Component
Approach to Highly Fluorescent Pyrrolo[2,3-b]pyridines, [1,8]Naphthyridines, and
Pyrido[2,3-b]azepines”, Oana G. Schramm neé Dediu, Thomas Oeser, Thomas J. J.
Müller, J. Org. Chem. 2006, 71(9), 3494−3500.

4. “Microwave-Accelerated Coupling-Isomerisation-Enamine Addition-Aldol Condensation
Sequences to 1-Acetyl-2-amino-cyclohexa-1,3-dienes”, Oana G. Schramm neé Dediu,
Thomas J. J. Müller Synlett. 2006, accepted.











Additionally, parts of this thesis were presented in form of oral contribution or posters:

Oral Contribution

“Microwave Deviating Effects in Consecutive One-Pot Syntheses based on Coupling-
Isomerisation Reaction (CIR)”, 14-23 Oktober 2005, New Methodology and Techniques in
Organic Chemistry: Sustainable Development in a Secure Environment (NeMeTOC), NATO
Workshop, Certosa di Pontigniano (Siena), Italy.

Posters

1. “Novel [3+2+1] and [3+3] One-Pot Syntheses of Highly substituted Pyridines and
Dihydropyridines”, Heidelberg Forum of Molecular Catalysis, Heidelberg, Germany, 2003,
abstracts.
2. “Novel Three-Component One-Pot Syntheses of Tetrahydro [1,8] Naphthyridines and
Azepines Based upon CIR”, Vortragstagung der Liebig-Vereinigung für Organische Chemie
(ORCHEM), Bad Nauheim, Germany, 2004, abstracts.
3. “Microwave-Assisted Coupling-Isomerization-Enamine MCR-Syntheses – Effects in
Consecutive One-Pot Reactions”, Heidelberg Forum of Molecular Catalysis, Heidelberg,
Germany, 2005, abstracts.









Abbreviations


Ar aryl
nBu n-butyl
Boc tert-butoxycarbonyl
COSY correlated spectroscopy
d doublet
DBU 1,8-diazabicyclo[5.4.0]undec-7-ene
dd doublet of doublets
ddd doublet of doublets of doublets
DMF N,N-dimethylforamide
DMSO dimethyl sulfoxide
ee enantiomeric excess
eq equivalent
EDG electron-donating group
EWG electron-withdrawing group
HOMO highest occupied molecular orbital
HRMS high resolution mass spectrometry
Hz hertz
LUMO lowest unoccupied molecular orbital
m multiplet
NMR nuclear magnetic resonance
Nu nucleophile
Ph phenyl
s singlet
t triplet
TBD 1,5,7-triazabicyclo[4.4.0]dec-5-ene
THF tetrahydrofuran
TLC thin-layer chromatography


1 Summary 1
1 Summary........................................................................................................................3
2 Zusammenfassung.........................................................................................................8
3 Introduction.................................................................................................................13
4 General Part − Results and Discussion........................................................................17
4.1 Chalcones − Natural and Synthetic Compounds, Versatile Synthons for Cycloaddition
Reactions .................................................................................................................................... 17
4.1.1 Chalcones − Literature Review ......................................................................................................17
4.1.2 Chalcone Synthesis – Literature Review........................................................................................20
4.1.3 Reactions of Chalcones ..................................................................................................................23
4.1.4 Synthesis of Chalcones via Sonogashira Coupling-Isomerization Reaction ..................................25
4.1.5 Microwave Assisted Coupling–Isomerization Reaction (MACIR) – Towards a General CIR ......28
4.2 [3+2+1] Pyridine Derivatives Synthesis Based upon CIR ..................................................... 45
4.2.1 Pyridines – Literature Review........................................................................................................45
4.2.2 One-Pot Four-Component CIR-Enamine Addition-Cyclocondensation Pyridine Synthesis .........50
4.3 [3+3] Dihydropyridine and Pyridine Syntheses Based upon CIR ........................................ 63
4.3.1 Dihydropyridines – Literature Review...........................................................................................63
4.3.2 One-Pot Three-Component CIR-Enamine Addition-Cyclocondensation Dihydropyridine and
Pyridine Syntheses........................................................................................................................................65
4.4 [4+2] 2-Ethoxy Pyridine Synthesis Based upon CIR............................................................. 70
4.4.1 Synthesis of N-Propargyl Tosyl Amides ........................................................................................70
4.4.2 Enimine Synthesis Based upon CIR...............................................................................................71