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  • 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.

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    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