Rights / License: Research Collection In Copyright - Non ... 1.1 Concepts of chirality ... 1.3...
date post
18-Aug-2020Category
Documents
view
0download
0
Embed Size (px)
Transcript of Rights / License: Research Collection In Copyright - Non ... 1.1 Concepts of chirality ... 1.3...
Research Collection
Doctoral Thesis
Heterogeneous enantioselective hydrogenation of α-keto esters and fluorinated ketones over chirally modified platinum
Author(s): Diezi, Simon
Publication Date: 2006
Permanent Link: https://doi.org/10.3929/ethz-a-005164493
Rights / License: In Copyright - Non-Commercial Use Permitted
This page was generated automatically upon download from the ETH Zurich Research Collection. For more information please consult the Terms of use.
ETH Library
https://doi.org/10.3929/ethz-a-005164493 http://rightsstatements.org/page/InC-NC/1.0/ https://www.research-collection.ethz.ch https://www.research-collection.ethz.ch/terms-of-use
Diss. ETH No 16541
0Heterogeneous Enantioselective
0Hydrogenation of α-Keto Esters and
0Fluorinated Ketones over
0Chirally Modified Platinum
A dissertation submitted to the
Swiss Federal Institute of Technology (ETH), Zurich
for the degree of Doctor of Natural Sciences
presented by
Simon Diezi
Dipl. Chem. ETH
born 12 March 1977
citizen of Thal (SG)
accepted on the recommendation of
Prof. Dr. A. Baiker, examiner
Prof. Dr. A. Togni, co-examiner
2006
für meine Eltern Huldi und Jürg†
in Liebe und Dankbarkeit
0
0Acknowledgment
Firstly, I would like to express my sincere gratitude to Prof. Dr. A. Baiker for his
support, both personally and scientifically, and the opportunity to complete
my doctoral studies in his group.
Moreover, I would like to thanks Prof. Dr. A. Togni for accepting the task
of co-examiner in this thesis.
I furthermore thank to Dr. T. Mallat for constructive discussions, his valu-
able suggestions and the big help during the past four years, Dr. A. Vargas for
his contributions to the modelling and calculations, and Dr. D. Ferri for the
spectroscopic part of this thesis.
Special thanks to M. Hess and S. Reimann for the valuable contributions
to this work during their diploma work.
Furthermore, I would like to thank for the contribution to the present
work: F. Bangerter for recording NMR spectra and his refreshing comments on
scientific research; U. Krebs for his help with fine mechanics and M. Wohl-
wend for electronic support.
A very big thank is dedicated to my office-mates Dr. M. Rohr, M. Ramin,
M. Caravati and Dr. M. Burgener for sharing many joyful moments in- and
outside the ETH, for the interesting talks and discussions, and all the personal
and scientific support which was essential to me.
vi
Additionally, I thank the whole Baiker-group for the unique atmosphere.
Specially I would like to mention the following members for sharing a lot of
good times and unforgettable moments: Dr. R. Hess, Dr. A. Gisler, Dr. L.
Schmid, Dr. C. Beck, Dr. M. S. Schneider, Dr. W.-R. Huck, F. Jutz and N. van
Vegten.
Financial support of this work by the Swiss National Science Foundation is
kindly acknowledged.
Finally, I would like to thank my family and Mandy for their love and sup-
port throughout all these years of my education.
ix
0
0Table of contents
Acknowledgment ......................................................................................................v
Table of contents.......................................................................................................ix
Summary .................................................................................................................. xv
Zusammenfassung .................................................................................................. xxi
1 Introduction ..............................................................................................................1
1.1 Concepts of chirality .......................................................................................1
1.2 Biological significance of chirality ................................................................3
1.3 Market of chiral pharmaceuticals ..................................................................5
1.4 Methods for the production of enantiopure compounds ........................5
1.4.1 Chiral pool and biosynthesis ..............................................................6
1.4.2 Starting from the racemate - resolutions ..........................................6
1.4.3 Asymmetric synthesis ...........................................................................9 Biocatalysis .........................................................................................10 Homogeneous enantioselective catalysis ............................................11 Heterogeneous enantioselective catalysis ...........................................12
1.5 Pt/cinchona alkaloid system ........................................................................12
1.5.1 Modifiers and solvents .......................................................................13
1.5.2 Activated ketones as substrates .........................................................15
1.5.3 Catalysts ...............................................................................................18
1.6 Aim of the thesis ............................................................................................19
1.7 References ........................................................................................................19
x
2 Inversion of enantioselectivity in the hydrogenation of ketopantolactone on
platinum modified by ether derivatives of cinchonidine ...................................27
2.1 Summary .........................................................................................................27
2.2 Introduction ....................................................................................................27
2.3 Experimental ...................................................................................................29
2.3.1 Catalytic hydrogenation ....................................................................29
2.3.2 Synthesis of O-substituted cinchonidines ......................................30 O-Methyl-cinchonidine (MeOCD) .....................................................30 O-Ethyl-cinchonidine (EtOCD) ..........................................................31 O-Trimethylsilyl-cinchonidine (TMSOCD) .......................................31 O-Phenyl-cinchonidine (PhOCD) .......................................................31
2.4 Results and discussion ...................................................................................32
2.5 Conclusions .....................................................................................................36
2.6 References ........................................................................................................37
3 Fine tuning the “chiral sites” on solid enantioselective catalysts ....................41
3.1 Summary .........................................................................................................41
3.2 Introduction ....................................................................................................42
3.3 Experimental ...................................................................................................46
3.3.1 Materials ...............................................................................................46
3.3.2 Synthesis of ether derivatives of CD ...............................................46 O-(1-Naphthyl)cinchonidine (NaphOCD) ..........................................46 O-(3,5-Dimethylphenyl)cinchonidine (XylOCD) ..............................47 O-[3,5-Bis(trifluoromethyl)phenyl]cinchonidine (HFXylOCD) ........47
3.3.3 Catalytic hydrogenations ..................................................................47
3.3.4 Spectroscopic methods ......................................................................48
3.4 Results and discussion ...................................................................................48
3.4.1 Inversion of enantioselectivity ........................................................48
3.4.2 Stability of ether derivatives of cinchonidine under reaction con-
ditions ...................................................................................................53
3.4.3 Nonlinear behavior of modifier mixtures ......................................57
3.4.4 UV-Vis study of modifier adsorption and hydrogenation ........61
3.4.5 Mechanistic considerations ...............................................................65
3.5 Conclusions .....................................................................................................67
3.6 References ........................................................................................................68
xi
4 An efficient synthetic chiral modifier for platinum ...........................................73
4.1 Summary .........................................................................................................73
4.2 Introduction ....................................................................................................73