Novel enantiopure {β-amino [beta-amino] alcohols and {β-amino [beta-amino] thiols in asymmetric catalysis [Elektronische Ressource] / vorgelegt von Toni Rantanen

Toni Di Troia

Informations

• Publié par: rheinisch-westfalischen_technischen_hochschule_-rwth-_aachen
• Publié le: 01 janvier 2007
• Nombre de lectures: 7
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Novel Enantiopure β-Amino Alcohols and β-Amino Thiols in
Asymmetric Catalysis




Von der Fakultät für Mathematik, Informatik und Naturwissenschaften der Rheinisch-
Westfälischen Technischen Hochschule Aachen zur Erlangung des
akademischen Grades eines Doktors der Naturwissenschaften genehmigte Dissertation


vorgelegt von
M. Sc.
Toni Rantanen


Aus Turku (Finnland)


Berichter: Universitätsprofessor Prof. Dr. C. Bolm
Universitätsprofessor Prof. Dr. D. Enders



Tag der mündlichen Prüfung: 07.05.2007




Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online verfügbar
The work presented in this thesis was carried out at the Institute of Organic Chemistry of RWTH
Aachen University between February 2004 and January 2007 under the supervision of Prof. Dr.
Carsten Bolm.

I would like to thank Prof. Dr. Carsten Bolm for the interesting research theme, the constant
support and useful discussions, as well as the ideal working atmosphere.

I would also like to thank Prof. Dr. Dieter Enders for his kind assumption of the co-reference.






Parts of this work have already been published:

1) I. Schiffers, T. Rantanen, F. Schmidt, W. Bergmans, L. Zani, C. Bolm
“Resolution of racemic 2-aminocyclohexanol derivatives and their application as ligands in
asymmetric catalysis”
J. Org. Chem. 2006, 71, 2320-2331.

2) B. Rodriguez, T. Rantanen, C. Bolm
“Solvent-free asymmetric organocatalysis in a ball mill”
Angew. Chem. 2006, 118, 7078-7080; Angew. Chem. Int. Ed. 2006, 45, 6924-6926.

3) T. Rantanen, I. Schiffers, C. Bolm
“Solvent-free asymmetric anhydride opening in a ball mill”
Org. Process Res. Dev. 2007, 11, 592-597, ASAP article.





1. Introduction ....................................................................................................... 1
1.1. Organocatalysis .....................................................................................................................4
1.1.1. Cinchona alkaloids .........................................................................................................8
1.1.1.1. Cinchona alkaloids in the desymmetrization of meso anhydrides...................11
1.1.1.2. Cinchona alkaloids in the asymmetric cyanation of simple ketones ...............16
1.1.1.3. Asymmetric conjugate addition catalyzed by cinchona alkaloids and
derivatives .............................................................................................................17
1.1.1.4. α-Halogenations catalyzed by cinchona alkaloids.............................................19
1.1.1.5. Morita-Baylis-Hillman reaction..........................................................................22
1.1.1.6. The asymmetric desymmetrization of meso diols..............................................23
1.1.2. Bifunctional cinchona catalysts...................................................................................24
1.2. New technologies in organic chemistry .............................................................................27
1.2.1. Microwaves ...................................................................................................................28
1.2.2. Mechanochemistry .......................................................................................................32
2. Research objectives.......................................................................................... 34
3. Results and discussion ..................................................................................... 37
3.1. Enantiopure β-amino alcohols ...........................................................................................37
3.1.1. Synthesis of cyclohexane based β-amino alcohols .....................................................38
3.1.2. β-Amino alcohols in the asymmetric aryl transfer reaction.....................................43
3.1.3. β-Amino alcohols as catalysts in the asymmetric desymmetrization of meso
anhydrides......................................................................................................................46
3.1.3.1. Acceleration by microwave irradiation..............................................................52
3.1.4. Testing the amino alcohols in other asymmetric transformations ..........................54
3.1.4.1. The asymmetric addition of thiols to enonens ...................................................54
3.1.4.2. The catalytic conjugate addition of α-phenyl-α-cyanoacetate to phenyl
vinyl sulfone ..........................................................................................................55
3.1.4.3. The asymmetric Henry reaction .........................................................................57
3.2. Ball milling...........................................................................................................................60
3.2.1. The solvent free desymmetrization of meso anhydrides...........................................60
3.2.2. The solvent free synthesis of α-amino acids in ball mill............................................67
3.3. The synthesis and applications of β-amino thiols .............................................................69
3.3.1. The synthesis of enantiopure cis-β-amino thiols........................................................69
3.3.2. The cis-amino thiols in the asymmetric transfer hydrogenation of prochiral
ketones ..........................................................................................................................76
3.4. Other attempts towards enantiomerically pure compounds...........................................85
3.4.1. The thio-cinchona alkaloids.........................................................................................85
3.4.2. Using the Burgess-reagent - a new route to enantiopure cis-diamines....................87
3.4.3. An attempt to synthesize some tetrazoles...................................................................90
4. Summary and outlook ......................................................................................92
5. Experimental Section....................................................................................... 96
5.1. General Remarks.................................................................................................................96
5.1.1. Solvents...........................................................................................................................96
5.1.2. Chemicals .......................................................................................................................97
5.1.3. Determination of the Physical Properties of the Synthesized Compounds..............97
5.1.4. Chromatographic Methods ..........................................................................................98
5.1.5. Synthetic Methodologies ...............................................................................................99
5.1.6. Compounds Prepared Following Literature Procedures ........................................100
5.2. General Synthetic Procedures..........................................................................................100
5.3. Synthesis of amino alcohols ..............................................................................................106
5.4. The asymmetric anhydride opening using amino alcohols as catalysts .......................122
5.5. The asymmetric anhydride opening in ball mill.............................................................127
5.6. The synthesis of α-amino acids in ball mill .....................................................................139
5.7. The synthesis of β-amino thiols ........................................................................................142
5.8. The asymmetric transfer hydrogenation.........................................................................155
5.9. Other compounds synthesized..........................................................................................159
5.10. The asymmetric aryl transfer.........................................................................................167
6. Appendix ........................................................................................................ 168
6.1. List of Abbreviations.........................................................................................................168
6.2. List of Publications............................................................................................................171
6.3. Curriculum Vitae et Studiorum.......................................................................................173
6.4. Acknowledgements............................................................................................................174









1. Introduction

1. Introduction

Where does chirality come from? The word ´chirality´ comes from the Greek wor