Domino twofold Heck, 6π-electrocyclation [six pi-electrocyclation] and regioselective palladium(0)-catalyzed reactions of brominated indoles, furans, naphthoquinone and 2,4,5,6-tetrachloropyrimidine [Elektronische Ressource] / vorgelegt von Munawar Hussain

Domino twofold Heck, 6π-electrocyclation [six pi-electrocyclation] and regioselective palladium(0)-catalyzed reactions of brominated indoles, furans, naphthoquinone and 2,4,5,6-tetrachloropyrimidine [Elektronische Ressource] / vorgelegt von Munawar Hussain

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UNIVERSITÄT ROSTOCKDomino Twofold Heck / 6π-Electrocyclization and Regioselective Palladium(0)-Catalyzed Reactions of Brominated Indoles, Furans, Naphthoquinone and 2,4,5,6-Tetrachloropyrimidine Dissertation zur Erlangung des Doktorgrades doctor rerum naturalium (Dr. rer. nat.) der Mathematisch-Naturwissenschaftlichen Fakultät der Universität Rostock vorgelegt von Munawar Hussain geb. am 05. Jan 1977 Khanpur, Rahim Yar Khan, Pakistan. Rostock, Juli 2010 urn:nbn:de:gbv:28-diss2011-0021-7Die vorliegende Arbeit entstand in der Zeit von April 2008 bis April 2010 am Institut für Chemie der Universität Rostock. Erinreichung der Dissertation: 1. Gutachter: Prof. Dr. Peter Langer, Universität Rostock, Germany 2. Gutachter: Prof. Dr. Scott Taylor, University of Waterloo, Canada 3. Gutachter: Prof. Dr. Willi Kantlehner, Hochschule Aalen, Germany thTag der Abgabe: 17 Juli, 2010 thRigorosum: 11 Januar, 2011 Wissenschaftliches Kolloquium: “I feel a great pleasure to dedicate all of this work to my respected mentor Abu Bilal Mohammad Ilyas Attar Qadri then my all teachers from I learned and will learn even a single word and my dear parents.Acknowledgements Alhamdolillahi First of AlI I pay my infinite thanks to Almighty Allah Azzawajal who Rabbil Aalamin blessed me with the chance and courage to complete this memorable Wassalatusalam task.

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UNIVERSITÄT ROSTOCK
Domino Twofold Heck / 6π-Electrocyclization and Regioselective
Palladium(0)-Catalyzed Reactions of Brominated Indoles, Furans,
Naphthoquinone and 2,4,5,6-Tetrachloropyrimidine
Dissertation
zur
Erlangung des Doktorgrades
doctor rerum naturalium (Dr. rer. nat.)
der Mathematisch-Naturwissenschaftlichen Fakultät
der Universität Rostock
vorgelegt von
Munawar Hussain geb. am 05. Jan 1977 Khanpur, Rahim Yar Khan, Pakistan.
Rostock, Juli 2010
urn:nbn:de:gbv:28-diss2011-0021-7Die vorliegende Arbeit entstand in der Zeit von April 2008 bis April 2010 am
Institut für Chemie der Universität Rostock.
Erinreichung der Dissertation:
1. Gutachter: Prof. Dr. Peter Langer, Universität Rostock, Germany
2. Gutachter: Prof. Dr. Scott Taylor, University of Waterloo, Canada
3. Gutachter: Prof. Dr. Willi Kantlehner, Hochschule Aalen, Germany
thTag der Abgabe: 17 Juli, 2010
thRigorosum: 11 Januar, 2011

Wissenschaftliches Kolloquium:
“I feel a great pleasure to dedicate all of this work
to my respected mentor Abu Bilal Mohammad Ilyas Attar
Qadri then my all teachers from I learned and will
learn even a single word and my dear parents.Acknowledgements
Alhamdolillahi First of AlI I pay my infinite thanks to Almighty Allah Azzawajal who
Rabbil Aalamin blessed me with the chance and courage to complete this memorable
Wassalatusalam task. And then Prophet Mohammad (Sallallah ho alai hi wasallam)
un Ala Rasool- whose personality is like a light through which each and everybody can
e-hilkarim examine his good and bad deeds.
I wish to present my thanks to all who added to the successful
completion of my Ph.D.
I feel it due, to pay my thanks to Prof. Dr. Peter Langer, my Ph.D.
Danke
supervisor, for providing efficient guidance and energetic research
environment during the whole Ph.D studies . I always found him ready
to facilitate my research, by effective discussions, reviving
encouragements, unending trust, providing free hand in research and
access to every possible facility.
Particularly, many thanks to my father Hakim Ali Nawaz who is an
Shukriah experienced herbal medicine physician in Pakistan. He is the person
who taught me how to think. Actually my all interest and hence
achievements in research are due to his inspiration and training
My special thanks to Dr. Yong Liu due to his exceptional support and

company during my stay in University of Waterloo Canada, in fact he
contributed very much in my practical and theoretical understanding.
I wish to express my special gratitude to Dr. Martin Hein and Dr. Dirk
Thank you
Michalik for a number of nice talks about my research, to Dr. Holger

Feist for his passion to deliver security instructions and making sure the
security, to Dr. Alexander Villinger for their professional and accurate
measuring X-ray crytallographic analyses. I would also like to thank
the members of NMR, IR, UV, MS, and X-ray laboratories of the
University of Rostock and the Leibniz Institute for Catalysis Rostock.
Acknowledgements are made to Dr. Rasheed Ahmad for introducing
such a nice research group and taking care of my arrival problems.
I am thankful to all my past and present, foreign and native colleagues
which I have missed here to mention for their research discussions, nice
company and time.
Many thanks to Dr. Tung T. Dang, Rasheed Ahmad Khera, N. T. Hung, Vielen Dank
Dhafer Saber Zinad, Asad Ali, Omer Akravi, Imran Malik, Muhammad
Nawaz, S. M. T. Toguem, Ghazwan Ali Salman, Dr. Inam Iqbal, Dr.
Imran Iqbal, Farooq Ibad, Ihsan Ullah Marwat, Olumide Fatunsin, Mr.
Sharif and all my other colleagues for their contribution and co-
operation.
I thank to my all countrymen especially Asif Attari, Mohammad
Thanks a lot
Nadeem Qadri, Abid Hussain Attari, Aamir Attari, Saeed Ahmad Attari, javed Iqbal Attari, Ahmad akram Attari and all other Pakistanis
in all parts of Germany particularly in Hamburg, Frankfurt, Berlin and
Rostock as their love, readiness to help and meaningful company gave
me not only support but also feeling like my own country and city
which made my stay here enjoyable.
It is not possible to forget to pay thanks the leaders and staff of Higher
Danke schön
Education Commission Pakistan particularly Ms. Saima Naurin for her
dedication to support and facilitate me in all related problems. Financial
support for my Ph.D. from Higher Education Commission of Pakistan
and Mecklenburg State, Germany is gratefully acknowledged.
Special thanks to all of my teachers for their education and training in Many Thanks
both life and chemistry, especially Dr. Zaheer Ahmad and Dr. Scott D.
Taylor as I started my research life with them.
I would like to convey my heartiest thanks to my whole family for their
love, support and adherence to my achievements and struggle. The
significance of their support and help in past and present cannot be
expressed in words.
I owe all of them in my life! MAIN CONTENTS
SUMMARY Page 1
CHAPTER 1 Page 2 - 5
An Overview of Domino Twofold Heck / 6π-Electrocyclization Reactions of 1,2-
Dihalogenated Compounds
RBr An overview of domino twofold Heck / 6π-R
electrocyclization reactions of vicinal
Pd[0] RX dihalides is given.
X=Br, OTf
CHAPTER 2 Page 6 - 17
Synthesis of 1,2-Dihydrocarbazoles and Carbazoles by Domino ′Twofold Heck / 6π-
′′
Electrocyclization′′′ Reactions of Di- and Tri-N-methylindoles
CO R The palladium(0)-catalyzed Heck cross-2Br
CO R coupling reactions of di- and tribromo-N-2
CO R2
Br methylindoles provided 1,2-
N N dihydrocarbazoles by a domino ′twofold
Me Me Heck / 6π-electrocyclization process at 120
°C. The products were transformed by
Pd/C-catalyzed oxidation to the
corresponding carbazoles.
CHAPTER 3 Page 18 - 21
Efficient Synthesis of Functionalized Benzofurans by Domino ′′′′Twofold Heck / 6ππππ-
Electrocyclization′′′ Reactions
I have synthesized functionalized
Br benzofurans based on domino ′twofold RR
Heck / 6π-electrocyclization′ reactions.
OO R Regioeselectivity issues of Heck cross Br
coupling have also been addressed.
Page 22 - 28CHAPTER 4
ISynthesis of Anthraquinones, Fluorenones and Benzocoumarins by Domino ′′′′Twofold
Heck / 6π-Electrocyclization′ Reactions ′′
O Functionalized anthraquinones, fluorenones O
R and benzocoumarins were prepared by Br R
domino ′twofold Heck / 6π-
Pd[0] R electrocyclization′ reactions. X
X=Br, OTf
CHAPTER 5 Page 29 - 38
Synthesis of Aryl-Substituted Pyrimidines by Site-Selective Suzuki-Miyaura Cross-
Coupling Reactions of 2,4,5,6-Tetrachloropyrimidine

Suzuki-Miyaura cross coupling reactions of
Cl Cl 2,4,5,6-tetrachloropyrimidine provide an
Cl Ar Ar Ar expedient synthesis of mono-, di-, tri- and
NN NN tetraarylpyrimidines which are not readily Cl
ArB(OH)2 Cl available by other methods. All reactions ClCl Cl
(1.0-4.4 equiv.) (1.0 equiv.) (2.0 equiv.) proceed with excellent site-selectivity.
NN
Cl Ar[Pd] Optimization of reaction conditions for better
Ar ArCl Ar Ar
yields and loading of lower percentage of
NN NN catalyst were studied as well.
Ar Ar
(3.0 equiv.) (4.4 equiv.)
CHAPTER 6 Page 39 – 45
Site-Selective Suzuki-Miyaura Cross-Coupling Reactions of 2,3,4,5-Tetrabromofuran
Suzuki-Miyaura reactions of 2,3,4,5-
Br
Br tetrabromofuran allowed a convenient
Ar synthesis of tetraarylfurans which are
O Ar
not readily available by other methods. (2.0 equiv.)Br ArB(OH)2Br Regioselectivity was achieved by using
(1.0-4.4 equiv.)
Br Ar the binary solvent system [Pd] ArO Br
Ar toluene/dioxane (4:1) at C-2, C-5 and
O
Ar then C-3, C-4. All reactions proceeded
(4.4 equiv.) with excellent yields and site-
selectivity.
IIEXPERIMENTAL SECTION Page 49 - 101
APPENDIX Page 102
ERKLÄRUNG Page 109
Page 110CURRICULUM VITAE
Page 116REFERENCE
DETAILED CONTENTS
1 An Overview of Domino Twofold Heck/ 6π-Electrocyclization Reactions of 1,2-
Dihalogenated Compounds ............................................................................................ 2
1.1 Pericyclic reactions 2
1.2 My research objectives ........................................................................................ 5
2 Synthesis of 1,2-Dihydrocarbazoles and Carbazoles by Domino ′Twofold Heck / 6π-
Electrocyclization′ Reactions of Di- and Tri-N-methylindoles.
2.1 Introduction ......................................................................................................... 6
2.2 Results and Discussion 7
2.3 Conclusion......................................................................................................... 17
3 Efficient Synthesis of Functionalized Benzofurans by Domino ′Twofold Heck / 6π-
Electrocyclization′ Reactions ..................................................................................... 18
3.1 Introduction ....................................................................................................... 18
3.2 Results and Discussion ......................................................................................
3.3 Conclusion......................................................................................................... 21
4 Synthesis of Anthraquinones, Fluorenones and Benzocoumarins by Domino ′Twofold
Heck / 6π-Electrocyclization′ Reactions ...................................................................... 22
4.1 Introduction 22
4.2 Results and Discussion 23
4.3 Conclusion......................................................................................................... 28
5 Synthesis of Aryl-Substituted Pyrimidines by Site-Selective Suzuki-Miyaura Cross
Coupling Reactions of 2,4,5,6-Tetrachloropyrimidine ............................................... 29
5.1 Introduction ....................................................................................................... 29
5.2 Results and Discussion ...................................................................................... 30
5.3 Conclusion......................................................................................................... 38
6 Site-Selective Suzuki-Miyaura Cross-Coupling Reactions of 2,3,4,5-Tetrabromofuran
...................................................................................................................................... 39
6.1 Introduction 39
III6.2 Results and Discussion ...................................................................................... 40
6.3 Conclusion......................................................................................................... 45
7 Abstract.........................................................................................................................46
Experimental Section ............................................................................................................... 49
8 Material and Methods ................................................................................................... 49
8.1 General Remarks ............................................................................................... 49
8.2 Methods for Compound Characterization and Analysis ...................................
8.3 Chromatographic Methods ................................................................................ 51
9 General Procedures ...................................................................................................... 52
9.1 Synthesis of 1,2-Dihydrocarbazoles and Carbazoles by Domino ′Twofold Heck
/ 6π-Electrocyclization′ Reactions of Di- and Tri-N-methylindoles ................. 52
9.1.1 Synthesis of 2,3-dibromo-N-methylindoles ...................................................... 52
9.1.2 Synthesis of 2,3,6-tribromo-N-methylindoles .............................................. 52
9.1.3 Sy2,3-bis(alkenyl)-N-methylindoles ............................................ 53
9.1.4 Synthesis of 2,3-dihydrocarbazoles………………………………………..54
9.1.5 Synthesis of 3,4-disubstituted carbazoles………………………………… 59
9.1.6 Synthesis of 2-(2-cyanoethyl)-9-methyl-9H-carbazole-3-carbonitriles ...61
9.1.7 Synthesis of 6-bromo-2,3-bis(alkenyl)-N-methylindoles ………………….62 Synthesis of 6-alkenyl-2,3-dihydrocarbazoles…………………… …… .66
9.1.8 Synthesis of 6-alkenylcarbazoles……………………………………….…70
9.1.9 (2E,2'E)-Dibutyl 3,3'-(3-formyl-1-methyl-1H-indole-2,6-diyl)diacrylate... 85
9.2 Efficient Synthesis of Functionalized Benzofurans by Domino ′Twofold Heck /
6π-Electrocyclization′ Reactions .................................................................... 74
9.2.1 Synthesis of 2,3-bis(alkenyl)furans ............................................................. 74
9.2.2 Synthesis of 5,6-disubstituted benzofurans ................................................. 77
9.3 Synthesis of Anthraquinones, Fluorenones and Benzocoumarines by Domino
′Twofold Heck / 6π-Electrocyclization′ Reactions ........................................... 79
9.3.1 Synthesis of mono- and disubstituted anthraquinones ................................ 79
9.3.2 Synthesis of disubstituted fluorenone .......................................................... 81
9.3.3 Synthesis of disubstituted benzocoumarins 82
9.4 Synthesis of Aryl-Substituted Pyrimidines by Site-Selective Suzuki-Miyaura
Cross-Coupling Reactions of 2,4,5,6-Tetrachloropyrimidine ........................... 82
9.4.1 Synthesis of tetraaryl-pyrimidines ............................................................... 83
9.4.2 Synthesis of 2,4,6-triaryl-5-chloropyrimidines ........................................... 87
9.4.3 Synthesis of 4,6-diaryl-2,5-dichloropyrimidines 89
9.4.4 Synthesis of unsymmetrical 2,4,6-triar y l -5-chloro p y rimidines ................... 90
9.4.5 Syymmetrical 2,4,5,6-tetraaryl-pyrimidines .......................... 91
9.4.6 Synthesis of 4-aryl-2,5,6-trichloropyrimidines........................................... 92
9.4.7 One-pot synthesis of unsymmetrical 2,4,6-triaryl-5-chloropyrimidines 94
9.5 Site-Selective Suzuki-Miyaura Cross-Coupling Reactions of 2,3,4,5-
Tetrabromofuran ............................................................................................... 95
9.5.1 Synthesis of tetraarylfurans ........................................................................ 96
9.5.2 Synthesis of 2,5-diaryl-3,4-dibromofurans…………………………......100
Appendix ................................................................................................................................ 102
10 Crystallographic Data ................................................................................................. 102
Abbreviations ......................................................................................................................... 108
Erklärung ................................................................................................................................ 109
IV