Synthesis of new functionalized organocopper reagents via a halogen-copper exchange reaction [Elektronische Ressource] / von Xiaoyin Yang

Dissertation zur Erlangung des Doktorgrades
der Fakultät für Chemie und Pharmazie
der Ludwig-Maximilians-Universität München








Synthesis of New Functionalized Organocopper
Reagents via a Halogen-Copper Exchange Reaction








Von

Xiaoyin Yang




Aus

Henan, China




München 2005


Erklärung

Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29.
Januar 1998 von Professor Dr. Paul Knochel betreut.


Ehrenwörtliche Versicherung

Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe erarbeitet.


München, 15. November 2005







Xiaoyin Yang







Dissertation eingereicht am 15. November 2005

1. Gutachter: Prof. Dr. Paul Knochel
2. Gutachter: Prof. Dr. Thomas Lindel

Mündliche Prüfung am 16. December 2005


This work was carried out from September 2002 to October 2005 under the supervision of
Professor Dr. Paul Knochel at the Department Chemie und Pharmazie of the
Ludwig-Maximilians-Universität, München.



I would like to appreciate my supervisor Prof. Dr. Paul Knochel for giving me the
opportunity to do my Ph.D. in his group and his guidance in the course of scientific research
presented here. It is Prof. Dr. Paul Knochel who first led me into the wonderful world of
organometallic chemistry and trained me to become a researcher in this scientific field.

I am especially indebted to Prof. Dr. Thomas Lindel for agreeing to be my “Zweitgutachter”,
as well as Prof. Dr. Hendrik Zipse, Prof. Dr. Konstantin Karaghiosoff, Prof. Dr. Hans Rudolf
Pfaendler and Prof. Dr. Manfred Heuschmann for the interest shown in the present
manuscript by accepting to be referees.

Dr. Lutz Ackermann, Ralf Klötzing and Andrei Gavryshin I thank for their careful
correction of the manuscript.

I thank Ludwig-Maximilians-Universität, München for financial support.

Special thanks go to my lab mates Krystyna Becker, Dr. Frédéric Liron, Dimitri Denisenko,
Dr. Shuji Yasuki, Armin Stoll, Sebastian Kroll, and Simon Matthe for being great lab
members, especial for making the wonderful “war”.

Furthermore, I would like to thank all the students and post-docs that came and went
through my Ph. D. for their brief and lasting friendships, suggestions and sympathy, which
have made my time in Germany a pleasant and worthwhile experience. I would especially
like to thank Dr. Isabel Calaza, Dr. Helena Leuser, Dr. Ioannis Sapountzis, Wenwei Lin,
Hongjun Ren, Qingyuan Liu, Murthy Narasimha, Darunee Soorukram, Nadege Boudet,
Sylvie Perrone, Oliver Baron, Nina Gommermann, Tobias Korn, Flix Kop, Andreas
Althammer, and Ludwig Kaspar, for their patience and their precious help. Last but not least
I thank Dr Claudia Piazza who is not only a great chemist but also a good friend.

I would also like to thank Vladimir Malakov and Beatrix Cammelade for their help in
organizing everyday life in the lab, as well as to the analytical team, Dr. D. Stephenson, Dr.
C. Dubler, Dr. W. Spahl. B. Tschuk, I. Bruck, H. Schulz and G. Kaser for their invaluable
help.

Finally, I am grateful to my family, especially my wife Yin Wei for their love,
encouragement and understanding, as well as all of my friends for their friendship and
support throughout my Ph. D. –Thank you so much!


Part of this Ph. D. Thesis have been published:

1. Xiaoyin Yang, Thomas Rotter, Claudia Piazza, Paul Knochel, “Successive
Iodine-Magnesium or -Copper Exchange Reactions for the Selective Functionalization
of Polyhalogenated Aromatics” Organic Letters 2003, 8, 1229-1231.

2. Xiaoyin Yang, Paul Knochel, “Preparation and Reactions of Polyfunctional Magnesium
Arylcuprates Obtained by an Iodine-Copper Exchange” Synlett 2004, 1, 81-84.

3. M. Isabel Calaza, Xiaoyin Yang, Darunee Soorukram, Paul Knochel, “Stereoselective
S 2-Substitutions using Polyfunctional Lithium Arylcuprates Prepared by an N
Iodine-Copper Exchange” Organic Letters 2004, 8, 1229-1231.

4. Xiaoyin Yang, Andreas Althammer, Paul Knochel, “Selective Functionalized in Position
2 and 3 of Indole via an Iodine-Copper Exchange Reaction” Organic Letters 2004, 6,
1665-1667.

5. Xiaoyin Yang, Paul Knochel, “Preparation and Acylation of Polyfunctional Copper
Derivatives of 3-Iodoindazoles Leading to Polyfunctional 3-Acylindazoles” Synlett.
2004, 13, 2303-2306.

6. Paul Knochel, Xiaoyin Yang, Nina Gommermann, “Polyfunctional Organocopper
Reagents for Organic Synthesis” in P. Knochel (Ed.) Handbook of Functionalized
Organometallics, Wiley-VCH, Weinheim, 2005.


















To Yin, with love



THEORETICAL PART

1 Overview............................................................................................................................. 1
1.1 Historical Perspective and Types of Organocopper Reagents......................................................2
1.2 Preparation of Organocopper Reagents .......................................................................................7
1.3 Allylic Substitution Reactions of Or........................................................12
2 Objectives.......................................................................................................................... 14
3 Preparation of Functionalized Arylcuprates via Halogen-Copper Exchange and Their
Application in Allylic Substitution Reactions ........................................................................... 16
3.1 Introduction.............16
3.2 Successive I/Cu-Exchange Reactions for the Selective Functionalization of Polyhalogenated
Aromatics.............................................................................................................................................17
3.2 Preparation of Highly Functionalized Aryl Cuprates in the Presence of an Aldehyde Group ...22
3.3 Application of the Functionalized Aryl Cuprate in Allylic Substitution Reactions ...................24
4 Preparation of Functionalized Heteroaryl Cuprate Reagents via an Iodine-Copper
Exchange Reaction .................................................................................................................... 32
4.1 Introduction................................................................................................................................32
4.2 Selective Functionalization of Indole Derivatives via an I/Cu- Exchange Reaction .................33
4.3 Functionalization of Indazoles in Position 3 via an I/Cu-Exchange Reaction...........................40
4.4 Functionalization of Imidazoles via an I/Cu-exchange Reaction...............................................46
4.5 Preparation of Highly Functionalized Heteroaryl Cuprates in the Presence of an Aldehyde
Group ...................................................................................................................................................51
5 Preparation of Functionalized Alkenyl Cuprate Reagents via an Iodine-Copper
Exchange Reaction .................................................................................................................... 56
5.1 Introduction................................................................................................................................56
5.2 Functionalization of β-Iodo- α, β-unsaturated Esters via an I/Cu-Exchange Reaction ...............58
5.3 β-Iodo- α, βated Ketones via an I/Cu-Exchange Reaction............64
5.4 β-Iodo- α, β-unsaturated Aldehydes via ........71
5.5 Preparation of Other Alkenyl Cuprates via Iodine or Bromine-Copper Exchange Reaction.....72
6 Preparation and Reactions of Polyfunctional Magnesium Arylcuprates Obtained by an
Iodine-Copper Exchange ........................................................................................................... 75
6.1 Introduction.............75
6.2 Attempts to Generate Functionalized Magnesium Cuprates via I/Cu-Exchange Reaction........75
7 Summary and Outlook ...................................................................................................... 83
7.1 Preparation of Functionalized Aryl Cuprates and Application in Allylic Substitution
Reactions..............................................................................................................................................83
7.2 Preparation of Functionalized Heterocyclic Cuprate Reagents..................................................85
7.3 Preparation of Functionalized Alkenyl Cuprates via Iodine or Bromine-Copper Exchange


Reaction...............................................................................................................................................86
7.4 Preparation and Reactions of Polyfunctional Magnesium Arylcuprates obtained by an
I/