Dissertation - Rostocker Do · PDF fileErinreichung der Dissertation: 01 Oktober 2011 1. ... Ernst-Moritz-Arndt Universität Greifswald Rigorosum: 04. ... to Dr. Holger Feist for his

Synthesis of Function

Tetrahyd

benzo[b]fluoren-

b]pyrroles, Benz

by Regioselect

Domi

Erla

docto

der Mathem

Ghazwan Ali S

nalized Benzofurans, Diaryl-Substitu

dro-9,10-Anthracen-1-ones, 5,10-Diar

-11-ones, Benzothieno[3,2-b]quinolin

zofuro[3,2-b]quinolines, and Furo[3,

tive Palladium(0)-Catalyzed Cross-C

ino C-N Coupling/Annulation Reacti

Dissertation zur

angung des akademischen Grades

or rerum naturalium (Dr. rer. nat.)

matisch-Naturwissenschaftlichen Fakult

der Universitt Rostock

vorgelegt von

alman geb. am 21. July 1979 Baghda

Rostock, September 2011

uted 1,2,3,4-

ryl-11H-

nes, Thieno[3,2-

,2-b]quinolines

Coupling and

ions

tt

ad, Iraq

urn:nbn:de:gbv:28-diss2012-0018-7

Die vorliegende Arbeit entstand in der Zeit von April 2009 bis August 2011 am

Institut fr Chemie der Universitt Rostock.

Dekan: Prof. Dr. Christoph Schick, Mathematisch-Naturwissenschaftliche

Fakultt, Universtt Rostock.

Erinreichung der Dissertation: 01 Oktober 2011

1. Gutachter: Prof. Dr. Dr. h.c. Peter Langer, Institut fr Chemie,

Universitt Rostock

2. Gutachter: Prof. Dr. Sabine Mller, Institut fr Bioorganic Chemie,

Ernst-Moritz-Arndt Universitt Greifswald

Rigorosum: 04. 01. 2012

Prfer Hauptfach: Prof. Dr. Dr. h.c. Peter Langer

(Institut fr Chemie, Universitt Rostock)

Prfer Nebenfach: Prof. Dr. Reinhard Schrder

(Institut fr Biowissenschaften, Universitt Rostock)

Tag der Promotion: 31. 01. 2012

Wissenschaftliches Kolloquium: 2012

Affectionately Dedicated to My dearest Father and Mother

for their exceptional love. Also, to my loving brothers and

sisters for their cares and support.

ACKNOWLEDGEMENTS

In the name of ALLAH, the beneficent, the merciful, who is Ubiquitous, Omniscient, worthy

of all praise, without his blessings and help this work would never been accomplished.

I feel great honor to express my utmost and sincere gratitude, appreciation, indebtedness to

Prof. Dr. Peter Langer for giving me the apportunity to carry out my Ph.D. research in his

research group and for providing efficient guidance and enerrgetic research environment

during whole Ph.D. I always found him ready to facilitate my research problems by effective

discussions, time devotion, unending trust and providing free hand in research.

My deapest thanks, and gratitude are extended to the Deutscher Akademischer Austausch

Dienst (DAAD) foundation for the generous financial support over three and a half past

years.

I wish to express my special gratitude to Dr. Martin Hein and Dr. Dirk Michalik for a number

of nice and valuable talks about my research, to Dr. Holger Feist for his enthusiasm to teach

about security instructions, to Dr. Alexander Villinger for their professional and accurate

measuring X-ray crystallographic analysis of my compounds. I would also like to thank the

members of NMR, IR, MS, and X-ray laboratories of the University of Rostock and the

Leibniz Institute for Catalysis Rostock.

I am thankful to all my past and present, foreigner and native colleagues of our research group

for their support, research discussions, and for the friendly atmosphere they provided.

Many thanks to my countryfellow and friends in Rostock (Dhafer Saber Zinad, Omer Akrawi,

Nadi Eleya), for their enjoyable and meaningful company gave me not only support but also

feeling like own country. I appreciate the support and help of Dr. Munawar Hussain during

the early days of my Ph.D. here at Rostock.

Finally I express my heartiest gratitude and respect to my mother and father, i have no words

to acknowledge their contribution in my life, especially full support during the whole period

of my life. I am fortunate enough to have such wonderful parents, without their constant

encourgement, love and support it would have been impossible for me to finish my studies. I

am also thankful to my dearest brothers and sisters who encouraged me through-out my

studies and support me what and whenever they could.

Ghazwan Ali Salman

August 2011, Rostock,

Germany

MAIN CONTENTS

SUMMARY page 1

CHAPTER 1 page 4 - 9

Synthesis of Functionalized Benzofurans by Double Heck Reactions of 2,3-dibromo-5-(ethoxycarbonyl)furan and subsequent 6-Electrocyclization / Dehydrogenation

The palladium(0)-catalyzed Heck cross-coupling reactions of 2,3-dibromo-5-(ethoxycarbonyl) furan provided functionalized 2,3-di(alkenyl)-5-(ethoxycarbonyl)furans by domino 'twofold Heck / 6 electrocyclization.The products were transformed to the corresponding functionalized benzofurans.

CHAPTER 2 Page 10 - 18

Regioselective Suzuki-Miyaura Reactions of the Bis(triflate) of 1,2,3,4-Tetrahydro-9,10-dihydroxyanthracen-1-one

Suzuki-Miyaura cross coupling reactions of the

bis(triflate) of 1,2,3,4 tetrahydro-9,10-

dihydroxyanthracen-1-one was proceeded with different

arylboronic acids to give mono- and diaryl 1,2,3,4-

tetrahydro-9,10-dihydroxyanthracen-1-one. The reaction

proceeded with very good site-selectivity in favour of

position 10, due to electronic reasons.

CHAPTER 3 Page 19 - 25

Site-selective Suzuki-Miyaura Reactions of the Bis(triflate) of 5,10-dihydroxy-11H-benzo[b]fluoren-11-one

The Suzuki-Miyaura reaction of the bis(triflate) of 5,10-dihydroxy-11H-benzo[b]fluoren-11-one with aryl boronic acids gave 5,10-diaryl-11H-benzo[b]fluoren-11-ones. The reaction with one equivalent of arylboronic acids resulted in site-selective attack at the more hindered and more electronically deficient carbon atom at C-10 and two different aryl groups were prepared by sequential addition of two different aryl boronic acids.

CHAPTER 4 Page 26 - 42

Domino C-N coupling / annulation versus C-N coupling / hydroamination of 2-alkynyl-

3-bromobenzothiophenes and 2-alkynyl-3-bromothiophenes. Highly efficient synthesis

of benzothieno[3,2-b]quinolines and thieno[3,2-b]pyrroles

While the palladium catalyzed

reaction of 2-alkynyl-3-

bromothiophenes with anilines

afforded thienopyrroles by a domino

C-N coupling / hydroamination

process, the reaction of 2-alkynyl-3-

bromobenzothiophenes with anilines

resulted, under identical conditions, in

the formation of

benzothienoquinolines by a domino

C-N coupling / annulation process.

The electronic character of the aniline

has an influence on the product

distribution.

CHAPTER 5 Page 43 - 51

Domino C-N Coupling / Annulation versus C-N Coupling / Hydroamination of 2-

Alkynyl-3-bromobenzofurans and 2-Alkynyl-3-bromofurans. Highly Efficient Synthesis

of Benzofuro[3,2-b]quinolines and Furo[3,2-b]quinolines The reaction of 2-alkynyl-3-

bromofuran and 2-alkynyl-3-

bromobenzofurans with electron rich

anilines afforded Furo[3,2-

b]quinolines and Benzofuro[3,2-

b]quinolones, respectively by a

domino C-N coupling / annulation

process, but with anilines containing

strong -acceptor substituents the

both substrates afforded Furo[3,2-

b]pyrrole and benzofuro[3,2-

b]pyrroles, respectively by a domino

C-N coupling / hydroamination

process.

EXPERIMENTAL SECTION Page 55 - 131

APPENDIX Page 132

ABBREVIATIONS Page 137

REFERENCES Page 138

ERKLRUNG Page 150

LIST OF PUBLICATIONS Page 151

DETAILED CONTENTS

1 Synthesis of Functionalized Benzofurans by Double Heck Reactions of 2,3-dibromo 5- (ethoxycarbonyl)furan and subsequent 6-Electrocyclization / Dehydrogenation 4

1.1 General Introduction. 4

1.2 Introduction . 6