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

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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