Synthesis of Functionalized Heterocycles Using Magnesium and Zinc Reagents [Elektronische Ressource] : Diastereoselective Addition of Allylic Aluminum Reagents to Carbonyl Compounds ; Preparation and Application of Aromatic and Benzylic Manganese Reagents / Zhihua Peng. Betreuer: Paul Knochel

Zhihua Peng

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2011
• Nombre de lectures: 18
• Langue: English
• Poids de l'ouvrage: 5 Mo

Extrait

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





Synthesis of Functionalized Heterocycles Using Magnesium and Zinc Reagents.
Diastereoselective Addition of Allylic Aluminum Reagents to Carbonyl
Compounds.
Preparation and Application of Aromatic and Benzylic Manganese Reagents




von

Zhihua Peng

aus

Shandong, China




2011 Erklärung
Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung
vom 29. Januar 1998 (in der Fassung der sechsten Änderungssatzung vom 16. August
2010) von Herrn Prof. Dr. Paul Knochel betreut.




Ehrenwörtliche Versicherung

Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe bearbeitet.


München, am 7. June 2011





…..……………………………………
Zhihua Peng








Dissertation eingereicht am 9. June 2011

1. Gutachter: Prof. Dr. Paul Knochel
2. Gutachter: Prof. Dr. Manfred Heuschmann

Mündliche Prüfung am 26. July 2011
This work was carried out from January 2008 to April 2011 under the guidance of
Prof. Dr. Paul Knochel at the Department Chemie und Pharmazie of the
Ludwig-Maximilians-Universität, Munich.

First, I would like to express my appreciation to Prof. Dr. Paul Knochel for giving me
the great opportunity to do my Ph.D. in his group and for his guidance and support in
the course of my scientific research.
I am also very grateful to Prof. Dr. Manfred Heuschmann for agreeing to be my
―Zweitgutachter‖ as well as Prof. Dr. Konstantin Karaghiosoff, Prof. Dr. Klaus
Wanner, Prof. Dr. Heinz Langhals and Prof. Dr. Rudolf Knorr for their interest shown
in this manuscript by accepting to be referees.
Furthermore, I would like to express my gratitude to Dr. Coura Diène for the careful
correction of this manuscript.
I thank all past and present co-workers I have met in the Knochel group for their
kindness, their help in every respect and the good times we had. Special thanks to my
actual and former lab mates Dr. Laurin Melzig, Dr. Andrei Gavryushin, Zhi-Liang
Shen, Dr. Anukul Jana, Dr. Georg Manolikakes, Dr. Shigeyuki Yamada, and Kohsuke
Kawabata.
Additional thanks go to Dr. Coura Diène, Matthias Schade, Andreas Wagner, Klaus
Groll, Thomas Kunz, Cora Dunst, Tomke Bresser, Gabriel Monzon, Tobias Thaler,
Andreas Steib, Christoph Sämann, Dr. Shun-Yi Wang, Dr. Shi Tang, Stephanie Seel,
Dr. Xavier Mollat du Jourdin, Dr. Alexei Bredihhin and Dr. Christina Despotopoulou
for being fantastic colleagues.
I would like to thank Dr. Benjamin Alexander Haag for the collaboration in the field
of 1,3,5-triazine and indazole chemistry. My thanks go to Tobias Blümke and
Zhi-Liang Shen for the cooperative work on the allylic aluminum chemistry.
I would also like to thank Vladimir Malakhov, Simon Matthe, Renate Schröder and
Yulia Tsvik for their help in organizing everyday life in the lab and in the office, as
well as the analytical team of the LMU for their invaluable help.
Special thanks to my friends Dr. Yi-Hung Chen, Dr. Ying-Hao Liu, Dr. Li-Na Guo,
Dr. Hong-Jun Gao, Dr. Zhi-Guang Zhang, and Dr. Zhi-Bing Dong for their friendship
and the nice time we spent together.
I would like to thank my family and my teachers in China for their great support,
throughout my studies and my Ph.D.
Finally, I thank my wife Yilei for her love and endless support.
Parts of this Ph.D. thesis have been published

1) Benjamin Haag, Zhihua Peng, and Paul Knochel*, Preparation of Polyfunctional
Indazoles and Heteroarylazo Compounds Using Highly Functionalized Zinc
Reagents, Org. Lett. 2009, 11, 4270-4273.
2) Tobias Blümke, Yi-Hung Chen, Zhihua Peng and Paul Knochel*, Preparation of
functionalized organoaluminiums by direct insertion of aluminium to unsaturated
halides, Nat. Chem. 2010, 2, 313-318.
3) Zhihua Peng, Benjamin A. Haag, and Paul Knochel*, Preparation of
2-Magnesiated 1,3,5-Triazines via an Iodine-Magnesium Exchange, Org. Lett.
2010, 12, 5398-5401.
4) Zhihua Peng, Tobias D. Blümke, Peter Mayer, and Paul Knochel*,
Diastereoselective Synthesis of Homoallylic Alcohols with Adjacent Tertiary and
Quaternary Centers by Using Functionalized Allylic Aluminum Reagents, Angew.
Chem. Int. Ed. 2010, 49, 8516 –8519.
5) Zhihua Peng, and Paul Knochel*, Preparation of Functionalized
Organomanganese(II) Reagents by Direct Insertion of Manganese to Aromatic and
Benzylic Halides, Org. Lett. 2011, 13, 3198-3201.

















To Yilei, with love

Table of Contents

A. General Introduction .............................................................................................. 1
1. Overview. ............................................................................................................... 1
2. Halogen-Metal Exchange Reaction. ...... 2
3. Allylic Aluminum Reagents .................. 9
3.1 Allylic Metals................................................................................................... 9
3.2 Allylic Aluminum Reagents .......... 13
4. Organomanganese Reagents ................................................................................ 17
4.1 Preparation of Organomanganese Reagents .................. 17
4.2 Reactions of Organomanganese Reagents ..................................................... 22
5. Objectives ............................................................................ 24
B. Results and Discussion .......................................................................................... 26
1. Preparation of 2-Magnesiated 1,3,5-Triazines via an Iodine-Magnesium
exchange ............................................................................................................ 26
1.1 Introduction: The Chemistry of 1,3,5-Triazine .............. 26
1.2 Preparation of Functionalized Iodotriazine Derivatives……. ....................... 28
1.3 Preparation of 2-Magnesiated 1,3,5-Triazines and Their Subsequent
Reactions with Various Electrophiles .......................................................... 32
1.4 Doubly Magnesiated 1,3,5-Triazine .............................. 37
1.5 Syntheses of Trimeric and Dimeric Derivatives ............................................ 38
1.6 Conclusion ..................................................................... 40
2. Preparation of Polyfunctional Indazoles Using Highly Functionalized Zinc
Reagents ............................................................................................................... 41
2.1 Synthetic Strategy .......................... 41
2.2 Preparation of Highly Functionalized Zinc Reagents .................................... 41
2.3 Preparation of Polyfunctionalized Indazoles ................. 43
2.4 Conclusion. .................................................................... 44
3. Diastereoselective Synthesis of Homoallylic Alcohols with Adjacent Tertiary
and Quaternary Centers by Using Functionalized Allylic Aluminum Reagents ... 45
3.1 Introduction .................................................................................................... 45
3.2 Preparation of Functionalized Allylic Chlorides ........... 47
3.3 Preparation of Functionalized Allylic Aluminum Reagents and Their
Addition to Aldehydes and Ketones ............................................................ 48
3.3.1 Cyclic Aluminum Reagents .................................. 48
3.3.2 Cinnamyl Aluminum Reagents ............................. 53
3.3.3 Cyano-Substituted Cyclopentylaluminum Reagent .............................. 55
3.3.4 β-Silyl-substituted Crotylaluminum Reagent ....................................... 56
3.4 Conclusion ..................................................................... 57
3.5 Extension of Functionalized Allylic Aluminum Reangents .......................... 58
3.5.1 Introduction ........................................................................................... 58
3.5.2. Preparation of Allylic Chlorides .......................... 59
3.5.3 Preparation of Allylic Aluminum Reagents and Their Addition to
Aldehydes and Ketones .......................................................................... 59
3.5.4 Conclusion ............................................................................................ 62
4. Preparation of Functionalized Organomanganese(II) Reagents by Direct
Insertion of Manganese to Aromatic and Benzylic halides ............................. 63
4.1 Introduction ................................................................................................ 63
4.2 Optimization of The Reaction Conditions ................................................. 64
4.3 Preparation of Aromatic Manganese Reagents .......... 65
4.4 Preparation of Benzylic Manganese Reagents ........................................... 68
4.5 Conclusion ..........