Synthesis of bridged and non-bridged N-heterocycles, dichloromethyl- and formyl-salicylates, pyran-4-ones, chromanes and isochromanes based on cyclocondensation reactions of 1,3-bis(silyloxy)-1,3-butadienes and oxime dianions [Elektronische Ressource] / vorgelegt von Vahuni Karapetyan

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• Publié par: universitat_rostock
• Publié le: 01 janvier 2009
• Nombre de lectures: 24
• Langue: English
• Poids de l'ouvrage: 6 Mo

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Synthesis of Bridged and Non-Bridged N-Heterocycles,
Dichloromethyl- and Formyl-Salicylates, Pyran-4-ones,
Chromanes and Isochromanes based on
Cyclocondensation Reactions of
1,3-Bis(silyloxy)-1,3-butadienes and Oxime Dianions
D I S S E R T A T I O N
Zur
Erlangung des akademischen Grades
doctor rerum naturalium (Dr. rer. nat.)
der Mathematisch-Naturwissenschaftlichen Fakultät
der Universität Rostock
vorgelegt von
Vahuni Karapetyan
geb. am 03. Januar 1984
Rostock, 23.09.2009
urn:nbn:de:gbv:28-diss2010-0033-9The presented work in this dissertation was carried out from October 2006 till October 2009
at the Institute of Chemistry at the University of Rostock.
Erstgutachter: Prof. Dr. Peter Langer, Institut für Chemie,
Universität Rostock, Germany
Zweitgutachter: Prof. Dr.Orazio A. Attanasi, Istituto di Chimica Organica,
Università degli Studi di Urbino “Carlo Bo”, Urbino, Italy
Tag der Verteidigung: 04.02.2010 Acknowledgements
I thank all those who contributed to the success of this work and who supported me
during my time as a Ph.D student.
Firstly with my great respect, I would like to thank my supervisor Prof. Dr. Peter Langer,
for providing me with the research topic, for his continuous support and insightful comments
on my work.
The analytical measurements in presented work were performed by analytical staff of the
Institute of Chemistry and Leibniz Institute for Catalysis at the University of Rostock. All
colleagues are gratefully acknowledged for their excellent cooperation. Among others my
special thanks to Dr. Dirk Michalik, and Brigitt Schimanski for NMR measurements, Prof. Dr.
Helmut Reinke and Dr. Alexander Villinger for X-ray studies, Dr. Christine Fischer for MS
measurements, and Angela Niemann for IR measurements.
I am thankful to all members of our research group, especially Anne Hallmann, Andreas
Schmidt, Satenik Mkrtchyan, Thomas Rahn, Jennifer Hefner, Alina Bunescu, Claudia Vinke,
Jörg-Peter Gütlein, Steffi Reim, Dang Thanh Tuan, Dennis Kleeblatt, Friedrich Erben for the
time and support they invested and for the awesome activities they organized.
Furthermore, I am really thanked to Dr. Martin Hein, Mathias Lubbe and Stefan Büttner
for the suggestions during writing my thesis.
My special thanks to Dr. Elena Bulanova and Dr. Vadim Budagian (Research Center
Borstel, Leibniz Center for Medicine and Biosciences, Germany) for the excellent scientific
and personal support that I received during my stay in Borstel.
I would like to express my gratitude to Prof. Dr. Aida Avetisyan (Faculty of Chemistry,
Yerevan State University, Armenia) and Prof. Dr. Gagik Hasratyan (Institute of Organic
Chemistry of NAS, Armenia) for their kind support.
Financial support from the State of Mecklenburg-Vorpommern (Germany) is gratefully
acknowledged.
I would like to thank all of my international friends spread all over the world.
Last but not least, I would like to express my sincere thanks to my family. Without their
love and support the achievement of this work would never be able to happen.
Thank You All Very Much!!!
Vahuni Karapetyan
October 2009, Rostock Table of Contents
Table of Contents
GENERAL INTRODUCTION ........................................................................................................................ - 1 -
1. 1,3-BIS(SILYLOXY)-1,3-BUTADIENES AS POWERFUL BUILDING BLOCKS ......................... - 3 -
1.1 REGIOSELECTIVITY FOR REACTIONS OF 1,3-BIS(SILYLOXY)-1,3-BUTADIENES ....................................... - 3 -
1.2 SYNTHESIS OF 1,3-BIS(SILYLOXY)-1,3-BUTADIENES .............................................................................. - 5 -
2. SYNTHESIS OF BRIDGED AND NON-BRIDGED N-HETEROCYCLES BASED ON
CYCLOCONDENSATION REACTIONS OF 1,3-BIS(SILYLOXY)-1,3-BUTADIENES ............... - 7 -
2.1 SYNTHESIS OF 3,4-BENZO-7-HYDROXY-2,9-DIAZABICYCLO[3.3.1]NON-7-ENES BY CYCLIZATION
OF 1,3-BIS(SILYLOXY)-1,3-BUTADIENS WITH QUINAZOLINES ................................................................. - 7 -
2.1.1 Introduction ................................................................................................................................. - 7 -
2.1.2 Synthesis of substituted quinazolines .......................................................................................... - 9 -
2.1.3 Synthesis of 3,4-benzo-7-hydroxy-2,9-diazabicyclo[3.3.1]non-7-enes ..................................... - 10 -
2.1.4 Mechanistic pathway of the synthesis
of 3,4-Benzo-7-hydroxy-2,9-diazabicyclo[3.3.1]non-7-enes .................................................... - 10 -
2.1.5 Products and yields.................................................................................................................... - 12 -
2.1.6 Suzuki cross-coupling reactions of the products ....................................................................... - 16 -
2.1.7 B3LYP/6-31G(d) density functional theory computation ......................................................... - 17 -
2.1.8 Synthesis of 6-(2-aminophenyl)-4-oxo-1,4,5,6-tetrahydropyridines and 8,12-diaza-
2,7tricyclo[7.3.1.0 ]trideca-2(7),3,5,10-tetraenes by reductive cleavage of the
benzyloxycarbonyl moiety asa protective group ...................................................................... - 20 -
2.1.9 Mechanistic pathway of the synthesis
2,7
of 8,12-diaza-tricyclo[7.3.1.0 ]trideca-2(7),3,5,10-tetraenes .................................................. - 22 -
2.2 REGIOSELECTIVE SYNTHESIS OF NEW 1-AMINOPYRROLES AND 1-AMINO-4,5,6,7-TETRAHYDROINDOLES
BY ONE-POT ′CONJUGATE ADDITION/CYCLIZATION′ REACTIONS
OF 1,3-BIS(SILYLOXY)-1,3-BUTADIENES WITH 1,2-DIAZA-1,3-BUTADIENES ........................................ - 25 -
2.2.1 Introduction ............................................................................................................................... - 25 -
2.2.2 Regioselective synthesis of new 1-aminopyrroles and 1-amino-4,5,6,7-tetrahydroindoles ...... - 26 -
2.2.3 Mechanistic pathway of the synthesis of 1-aminopyrroles ........................................................ - 28 -
2.2.4 Products and yields.................................................................................................................... - 29 -
2.3 CONCLUSIONS ...................................................................................................................................... - 33 -
3. SYNTHESIS OF FUNCTIONALIZED SALICYLATES AND PYRAN-4-ONES BASED ON [3+3]
CYCLIZATIONS OF 1,3-BIS(SILYLOXY)-1,3-BUTADIENES ..................................................... - 35 -
3.1 SYNTHESIS OF DICHLOROMETHYL- AND FORMYLSALICYLATES BASED ON REGIOSELECTIVE [3+3]
CYCLOCONDENSATIONS OF 1,3-BIS(SILYLOXY)-1,3-BUTADIENES ....................................................... - 35 -
3.1.1 Introduction ............................................................................................................................... - 35 -
3.1.2 Synthesis of starting materials ................................................................................................... - 37 -
3.1.2.1 Synthesis of 1,1-dichloro-4-ethoxy-3-buten-2-ones ........................................................ - 37 -
3.1.2.2 Synthesis of 1,1-dimethoxy-4,4-dichlorobut-1-en-3-one ................................................. - 38 -
3.1.3 Synthesis of 6-Dichloromethylsalicylates based on Regioselective [3+3] Cyclocondensations
of 1,3-Bis(silyloxy)-1,3-butadienes with 1,1-Dichloro-4-ethoxy-3-buten-2-ones ..................... - 39 -
3.1.4 Mechanistic pathway of the synthesis of 6-(dichloromethyl)-salicylates .................................. - 40 -
3.1.5 Products and yields.................................................................................................................... - 41 -
3.1.6 Synthesis of 6-Dichloromethylsalicylates based on Regioselective [3+3] Cyclocondensations
of 1,3-Bis(silyloxy)-1,3-butadienes with 1,1-Dimethoxy-4,4-dichlorobut-1-en-3-one ............. - 42 -
3.1.7 Products and yields.............. - 43 -
3.1.8 Synthesis of 6-formylsalicylates ............................................................................................... - 44 -
3.1.9 Synthesis of formylchromanes .................................................................................................. - 46 -
i Table of Contents
3.2 SYNTHESIS OF DICHLOROMETHYL-SUBSTITUTED PYRAN-4-ONES BY ME SIOTF-MEDIATED 3
CYCLOCONDENSATION OF 1,3-BIS(SILYLOXY)-1,3-BUTADIENES WITH 1,1-DIMETHOXY-4,4-
DICHLOROBUT-1-EN-3-ONE. ................................................................................................................. - 48 -
3.2.1 Introduction ............................................................................................................................... - 48 -
3.2.2 Synthesis of 2-(dichloromethyl)pyran-4-ones ........................................................................... - 50 -
3.2.3 Mechanistic pathway ................................................................................................................. - 50 -
3.2.4 Products and yields.................................................................................................................... - 51 -
3.3 CONCLUSIONS ................................................................