Multi-component reactions initiated via Sonogashira coupling [Elektronische Ressource] / vorgelegt von Alexei S. Karpov

Karpov

Informations

• Publié par: ruprecht-karls-universitat_heidelberg
• Publié le: 01 janvier 2005
• Nombre de lectures: 37
• Langue: English
• Poids de l'ouvrage: 6 Mo

Extrait

Inaugural-Dissertation




Zur Erlangung der Doktorwürde
der Naturwissenschaftlich-Mathematischen-Gesamtfakultät
der
Ruprecht-Karls-Universität
Heidelberg





vorgelegt von
M. Sc. Alexei S. Karpov
Aus Dzerzhinsk, Russland



Tag der Disputation:
15.04.05












Multi-component Reactions Initiated via
Sonogashira Coupling











Gutachter: Prof. Dr. Thomas J. J. Müller
Prof. Dr. Dr. h. c. Rolf Gleiter






































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




Heidelberg, im Februar 2005




Acknowledgements


Foremost, I would like to thank Prof. Dr. Thomas J. J. Müller for giving me a very interesting
subject of PhD thesis and providing me with a continuous support and a very kind
supervision.

I thank all my colleagues for their unfailing support and very good working conditions.

I am grateful to Mr. Daniel D’Souza for valuable advices during the preparation of this
manuscript and for helpful discussions throughout my work on this PhD thesis.

I would like to express my special thanks to Anja Reinhart for her help and patience during
the preparation of this manuscript.

I thank Mrs. Andrea Seehuber and Mr. Eugen Merkul for their interest and diligence during
their research practice and Mrs. Michaela Schmitt for her encouragement during the
experimental assistance.

I wish to thank 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. Bianca Flock, Mrs. Angelika Seith, Mr. Norbert Nieth, and Mr. Dr. Jürgen H. Gross for
mass spectra, Mrs. Vetter, and Mr. Liebscher for carrying out of elemental analyses, Mr. Dr.
Thomas Oeser and Mr. Dr. Frank Rominger for supplying with X-Ray structures, and Mr. Dr.
Dieter Dorsch from Merck KGaA for a measurement of biological activities of meridianins.

My special appreciation goes to my parents Sergey and Olga Karpov, my brother Andrey, my
sister Irina, and to all my friends for their general support during my work on this PhD thesis.



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


Publications

[1] “A Novel Three-component Synthesis of 2,5-Disubstituted β-halofurans”,
A. S. Karpov, E. Merkul, T. Oeser, T. J. J. Müller, 2005, submitted.

[2] “A Novel One-pot Four-component Access to Tetrahydro- β-carbolines by a Coupling-
amination-aza-annulation-Pictet-Spengler Sequence (CAAPS)”, A. S. Karpov, T. Oeser,
T. J. J. Müller, Chem. Commun. 2004, 1502-1503.

[3] “Straightforward Novel One-Pot Enaminone and Pyrimidine Syntheses by Coupling-
Addition-Cyclocondensation Sequences”, A. S. Karpov, T. J. J. Müller, Synthesis 2003, 2815-
2826.

[4] “New Entry to a Three-Component Pyrimidine Synthesis by TMS-Ynones via
Sonogashira Coupling”, A. S. Karpov, T. J. J. Müller, Org. Lett. 2003, 5, 3451-3454.

[5] “Facile One-Pot Coupling-Aminovinylation Approach to Push-Pull Chromophores:
Alkyne Activation by Sonogashira Coupling”, A. S. Karpov, F. Rominger, T. J. J. Müller, J.
Org. Chem. 2003, 68, 1503-1511.

[6] „Synthese von substituierten Heterocyclen, Carbocyclen und Enaminonen mittels
einer neuartigen Ein-Topf-Reaktion“, T. J. J. Müller, A. S. Karpov, Deutsches Patent,
Anmeldung 25. 6. 2003; DE 103 28 400.1.










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


Oral Contributions

[1] “Multi-component Reactions Initiated via Sonogashira Coupling”,
Weihnachtskolloquium, 13.12.2004, Heidelberg, Germany.

[2] “Alkynones via Sonogashira Coupling as An Entry to The Synthesis of Heterocycles”,
Tag der Organischen Chemie der Universität Stuttgart (Doktorandenseminar), 15.10.2004,
Stuttgart, Germany.


Posters

[1] “A Novel One-pot Four-component Coupling-amination-aza-annulation-Pictet-
Spengler (CAAPS) Sequence”, A. S. Karpov, T. J. J. Müller; 14th International Symposium
on Homogeneous Catalysis, München, Germany, 2004, Abstracts, p. 365.

[2] “Straightforward Novel One-Pot Enaminone and Pyrimidine Syntheses by Coupling-
Addition-Cyclocondensation Sequences”, A. S. Karpov, T. J. J. Müller; Heidelberg Forum of
Molecular Catalysis, Heidelberg, Germany, 2003, Abstracts, p. 81.

[3] “A Multicomponent Approach to Novel Push-Pull Chromophores”, A. S. Karpov, T. J.
J. Müller; XXXVth International Conference on Coordination Chemistry, Heidelberg,
Germany, 2002, Abstracts, p. 973.

[4] “A Multicomponent Approach to Novel Push-Pull Chromophores”, A. S. Karpov, T. J.
J. Müller; Fifth International Symposium on Functional π-Electron Systems, Ulm, Germany,
2002, Abstracts, p. 200.





Abbreviations



Acc- π acceptor-substituted conjugate π -system
Bn benzyl
nBu n-butyl
Boc tert-butoxycarbonyl
br broad
Cbz benzyloxycarbonyl
d doublet
dd doublet of doublets
ddd doublet of doublets of doublets
dspt doublet of septets
dt doublet of triplets
de diastereomeric excess
dreric ratio
ee enantiomeric excess
DFT density functional theory
DHP 3,4-dihydro-2H-pyran
DMAP 4-dimethylaminopyridine
DMF N,N-dimethylformamide
DMSO dimethyl sulfoxide
dppf diphenylphosphinoferrocene
EA ethyl acetate
ee enantiomeric excess
equiv equivalent
ESP electrostatic potential
EWG electron-withdrawing group
HE hexane
LA Lewis acid
LUMO lowest unoccupied molecular orbital
m multiplet
NBO natural bonding orbital
NMR nuclear magnetic resonance
Nu nucleophile
Ph phenyl
q quartet
s singlet
spt septet
t triplet
TBAF tetra-n-butylammonium fluoride
TBS tert-butyldimethylsilyl
TFA trifluoroacetic acid
TFAA trifluoroacetic anhydride
THF tetrahydrofuran
THP tetrahydropyranyl
TMS trimethylsilyl
TMSA trimethylsilyl acetylene

Table of Contents


1 Summary ________________________________________________________________ 1
2 Zusammenfassung_________________________________________________________ 7
3 Introduction_____________________________________________________________ 13
4 General Part – Results and Discussion _______________________________________ 17
4.1 Synthesis of Push-Pull Chromophores _________________________________________ 17
4.1.1 Michael Addition  Literature Review_______________________________________________ 17
4.1.2 Synthesis of Push-Pull Chromophores 20
4.1.3 Computational Studies on the Michael Addition 29
4.2 One-Pot Reactions Initiated via Sonogashira Coupling of Acid Chlorides ____________ 33
4.2.1 Ynones  Literature Review_______________________________________________________ 33
4.2.1.1 Synthesis of Ynones ___________________________________________________________ 34
4.2.1.2 Reactions of Ynones 37
4.2.2 Synthesis of (TMS)-ynones via Sonogashira Coupling and Subsequent One-pot Transformations_43
4.2.3 One-pot Synthesis of β-Enaminones and Pyrimidines by Coupling-Addition-Cyclocondensation
Sequences _________________________________________________________________________ 54
4.2.3.1 β-Enaminones – Literature Review ________________________________________________ 54
4.2.3.2 Synthesis of β-Enaminones via Coupling-Addition Sequence ___________________________ 58
4.2.3.3 Computational Studies on the Stereochemistry of β-Enaminone Formation_________________ 63
4.2.3.4 Pyrimidines – Literature Review__________________________________________________ 66
4.2.3.5 Synthesis of Pyrimidines via Coupling-Cyclocondensation Sequenc