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Publié par | ludwig-maximilians-universitat_munchen |
Publié le | 01 janvier 2007 |
Nombre de lectures | 31 |
Langue | English |
Extrait
Dissertation zur Erlangung des Doktorgrades
der Fakultät für Chemie und Pharmazie
der Ludwig-Maximilians-Universität München
Preparation and Reactions of Allylic Zinc Reagents
and
Transition Metal-Catalyzed Cross-Coupling Reactions
von
Guillaume Dunet
aus
Orléans, Frankreich
München 2007
Erklärung
Diese Dissertation wurde im Sinne von § 13 Abs.3 bzw. 4 der Promotionsordnung vom 29.
Januar 1998 von Herrn Prof. Dr. Paul Knochel betreut.
Ehrenwörtliche Versicherung
Diese Dissertation wurde selbständig, und ohne unerlaubte Hilfe erarbeitet.
München, am 15.11.2007
Guillaume Dunet
Dissertation eingereicht am 15.11.2007
1. Gutachter: Prof. Dr. Paul Knochel
2. Gutachter: Prof. Dr. Manfred Heuschmann
Mündliche Prüfung am 14.12.2007 This work was carried out from November 2004 to December 2007 under the guidance of
Prof. Paul Knochel at the Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-
Universität, Munich.
I would like to thank my supervisor, Prof. Dr. Paul Knochel, for giving me the opportunity of
doing my Ph.D. in his group.
I am also grateful to Prof. Dr. Manfred Heuschmann for agreeing to be my “Zweitgutachter”,
as well as Prof. Dr. H. Zipse, Prof. Dr. H. Langhals, and Prof. Dr. K. Karaghiosoff for the
interest shown in this manuscript by accepting to be referees.
I thank Dr. Sylvie Perrone and Dr. Giuliano Clososki for the careful correction of this
manuscript.
I would like to thank the DFG for financial support.
Special thanks to my actual and former lab mates: Hongjun, Genia, Pradipta, Subbu, Geogios,
Matt, Tobias and Alex for the great time we spent together in the lab.
I would like to thank Hongjun, Matt and Milica for the fruitful collaborations in the field of
the allylmetal chemistry.
I thank all past and present co-workers I have met in the Knochel’s group for the good times
we had (especially parties).
I would also like to thank Vladimir Malakhov, Beatrix Cammelade, Simon Matthe, and Yulia
Tsvik for their help in organizing everyday life in the lab, as well as the analytical team, Dr.
D. Stephenson, Dr. C. Dubler, Dr. W. Spahl, B. Tschuk, I. Brück, H. Schulz and G. Käser for
their help.
Very special thanks to Sylvie for her support, and for making this stay in Munich a lot more
entertaining :0)).
Finally I would like to thank my family and my friends for their great support, throughout my
time in Munich.
Parts of this Ph.D. thesis have been published:
1. Dunet, G.; Knochel, P. “Iron-Catalyzed Cross-Coupling between Alkenyl and Dienyl
Sulfonates and Functionalized Arylcopper Reagents” Synlett, 2006, 3, 407-410.
2. Dunet, G.; Knochel, P. “Highly Stereoselective Cobalt-Catalyzed Allylation of
Functionalized Diarylzinc Reagents” Synlett 2007, 9, 1383.
3. Ren, H.; Dunet, G.; Mayer, P.; Knochel, P. “Highly Diastereoselective synthesis of
Homoallylic Alcohols Bearing Adjacent Quaternary Centers Using Substituted Allylic
Zinc Reagents” J. Am. Chem. Soc. 2007, 129, 5376-5377.
4. Dunet, G.; Mayer, P.; Knochel,P. “Highly Diastereoselective Addition of
Cinnamylzinc Reagents to α-Chiral Carbonyl Derivatives” Org. Lett. In press
Après la pluie, le beau temps…
6
Table of Contents
THEORETICAL PART ......................................................................................................................................... 9
1. Introduction......................................................................................................................................... 10
1.1. Overview......................................................................................................................................... 10
1.1.1. Allylic zinc reagents ...................................................................................................................... 10
1.1.2. Cross-coupling reactions .............................................................................................................. 21
1.2. Objectives....................................................................................................................................... 29
3. LiCl-mediated preparation of allylic zinc reagents and their reaction with
electrophiles.............................................................................................................................................. 31
3.1. Introduction.................................................................................................................................... 31
3.2. LiCl-mediated preparation of allylic zinc reagents ............................................................ 32
3.3. Diastereoselective reaction of allylic zinc reagents with aldehydes and ketones...... 34
3.4. Reaction with α-chiral ketones................................................................................................. 40
3.4.1. Reaction with α-chiral cyclohexanones......................................................................................... 40
3.4.2. Reaction with acyclic α-chiral ketones.......................................................................................... 45
3.4.3. Application to enantioenriched α-chiral ketones .......................................................................... 46
3.5. Direct “zinc-ene” reaction from allylic chlorides ............................................................... 47
3.6. Conclusion...................................................................................................................................... 52
4. New transition metal-catalyzed cross-coupling reaction............................................ 54
4.1. Highly stereoselective cobalt-catalyzed allylation of functionalized diarylzinc
reagents.......................................................................................................................................................... 54
4.2. Iron-catalyzed cross-coupling between alkenyl and dienyl sulfonates and
functionalized arylcopper reagents........................................................................................................ 60
4.3. Nickel-catalyzed cross-coupling between aryl phosphates and arylmagnesium
reagents.......................................................................................................................................................... 65
5. Summary and outlook.................................................................................................................... 70
5.1. LiCl-mediated preparation of allylic zinc reagents and their reaction with
electrophiles ................................................................................................................................................. 70
5.2. Highly stereoselective cobalt-catalyzed allylation of functionalized diarylzinc
reagents.......................................................................................................................................................... 72 7
5.3. Iron-catalyzed cross-coupling between alkenyl and dienyl sulfonates and
functionalized arylcopper reagents........................................................................................................ 73
5.4. Nickel-catalyzed cross-coupling between aryl phosphates and arylmagnesium
reagents.......................................................................................................................................................... 74
EXPERIMENTAL PART .................................................................................................................................... 76
6. General considerations.................................................................................................................. 77
7. Preparation and reactions of allylic zinc reagents ......................................................... 81
7.1. Typical Procedures (TPs)........................................................................................................... 81
7.1.1. Typical procedure for the formation of allylic zinc reagents from allylic chlorides or phosphates
(TP1): ....................................................................................................................................................... 81
7.1.2. Typical procedure for the reaction of allylic zinc reagents with aldehydes, ketones or imines
(TP2): ....................................................................................................................................................... 81
7.1.3. Typical procedure for the intramolecular “zinc-ene” reaction (TP3):......................................... 82
7.2. Experimental section:...........................................................................