Phosphorus Ylides, Sulfur Ylides, and Related Carbanions ... Nucleophiles for the Quantification of the Electrophilic Reactivities of ... a direct comparison ... carbanions in DMSO

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  • Dissertation zur Erlangung des Doktorgrades

    der Fakultt fr Chemie und Pharmazie

    der Ludwig-Maximilians-Universitt Mnchen

    Phosphorus Ylides, Sulfur Ylides, and Related Carbanions as

    Reference Nucleophiles for the Quantification of the

    Electrophilic Reactivities of Aldehydes, Imines, and Enones

    Roland Joachim Appel

    aus Mnchen

    2011

  • Erklrung

    Diese Dissertation wurde im Sinne von 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29.

    Januar 1998 (in der Fassung der vierten nderungssatzung vom 26. November 2004) von

    Herrn Professor Dr. Herbert Mayr betreut.

    Ehrenwrtliche Versicherung

    Diese Dissertation wurde selbstndig, ohne unerlaubte Hilfe erarbeitet.

    Mnchen, 10.02.2011

    ____________________________

    Roland Appel

    Dissertation eingereicht am: 10.02.2011

    1.Gutachter: Prof. Dr. Herbert Mayr

    2.Gutachter: Prof. Dr. Manfred Heuschmann

    Mndliche Prfung am: 05.04.2011

  • FR MEINE ELTERN

  • Acknowledgment

    Acknowledgment

    First, I would like to express my deepest gratitude to Professor Dr. Mayr for giving me the

    opportunity to perform this thesis in his group. I have always appreciated the valuable

    discussions with him, his endless support, his expert knowledge in any field of chemistry, his

    inspiring confidence, and the possibility for a self-contained planning and presenting of

    projects. I really enjoyed working under these excellent conditions and I cannot

    overemphasize my gratitude for all the things I learned during this time.

    Furthermore, I want to thank Professor Dr. Heuschmann for reviewing this thesis and the

    board of examiners for their participation in my defense examination.

    The financial support by the Fonds der Chemischen Industrie (scholarship for PhD students)

    is gratefully acknowledged. Besides the funding for two years of my time during the PhD, this

    scholarship gave me the possibility to attend several international conferences.

    Furthermore, I would like to thank all my colleagues within the group of Professor Dr. Mayr

    (and the group of Dr. Konrad Koszinowski) for the great and pleasant working atmosphere,

    especially Dr. Tanja Kanzian, Dr. Sami Lakhdar, Dr. Martin Breugst, Christoph Nolte (The

    famous Olah-Lab-Crew), and Dr. Nicolas Streidl. I will never forget the great time with

    you, our professional and private conversations, and I hope that these friendships will

    continue in the future. Special thanks go to Dr. Sami Lakhdar for fantastic advices to plan my

    projects and for giving me the opportunity to see the most beautiful places of Tunesia on the

    occasion of the International Symposium of Modern Organic Chemistry (ISMOC) in

    Monastir 2009. I would also like to thank Nicolai Hartmann and Vasily Mezhnev for their

    great collaboration during their undergraduate research laboratories. Sincere thanks are given

    to Nathalie Hampel for synthesizing our reference electrophiles and for her original Bavarian

    charm, Brigitte Janker for solving any emerging problem, and Hildegard Lipfert for her

    never-ending help in organizational tasks. The excellent advices for improvement of

    manuscripts as well as the critical and valuable suggestions by Dr. Armin R. Ofial are

    gratefully acknowledged.

  • Acknowledgment

    Additionally, I want to thank my colleagues from the group of Professor Dr. Paul Knochel. I

    really have profited from their expertise in organometallic chemistry and I will never forget

    the great parties where I was always welcome.

    I am also very grateful for the support of all my friends and I want to thank particularly

    Sebastian Bernhardt and Garwin Pichler, who accompanied me throughout my chemistry

    studies. Your illustrious companionship always kept my spirits high during the sometimes

    exhausting daily routine of chemistry.

    For the efficient and fast proofreading of this thesis, I am very grateful to Dr. Martin Breugst,

    Dr. Tanja Kanzian, Dominik Allguer, Tobias Nigst, and Francisco Corral.

    Last but not least, I want to thank my family for the unique and fantastic support. I cannot

    overemphasize my gratitude for your help and encouragement. In particular, I am deeply

    indepted to my parents, who were backing me all the way. This thesis is dedicated to you!

    Thank you very much!

  • Publications

    Publications

    Nucleophilicities of the Anions of Arylacetonitriles and Arylpropionitriles in Dimethyl

    Sulfoxide

    O. Kaumanns, R. Appel, T. Lemek, F. Seeliger, H. Mayr, J. Org. Chem. 2009, 74, 75-81.

    Nucleophilicity Parameters for Phosphoryl-Stabilized Carbanions and Phosphorus

    Ylides: Implications for Wittig and Related Olefination Reactions

    R. Appel, R. Loos, H. Mayr, J. Am. Chem. Soc. 2009, 131, 704-714.

    How Does Electrostatic Activation Control Iminium Catalyzed Cyclopropanations?

    [Wie werden Iminium-katalysierte Cyclopropanierungen durch elektrostatische

    Aktivierung gesteuert?]

    S. Lakhdar, R. Appel, H. Mayr, Angew. Chem. 2009, 121, 5134-5137; Angew. Chem. Int. Ed.

    2009, 48, 5034-5037.

    Nucleophilic Reactivities of Sulfur Ylides and Related Carbanions: Comparison with

    Structurally Related Organophosphorus Compounds

    R. Appel, H. Mayr, Chem. Eur. J. 2010, 16, 8610-8614.

    Scope and Limitations of Cyclopropanations with Sulfur Ylides

    R. Appel, N. Hartmann, H. Mayr, J. Am. Chem. Soc. 2010, 132, 17894-17900.

    Quantification of the Electrophilic Reactivities of Aldehydes, Imines, and Enones

    R. Appel, H. Mayr, J. Am. Chem. Soc. 2011, submitted.

  • Conference Contributions

    Conference Contributions

    03/2008 1st workshop of the Sonderforschungsbereich 749, Wildbad Kreuth, Germany,

    oral presentation: Ambident Reactivity of ,-Unsaturated Carbonyl

    Compounds; From the Free Carbanion to the Organometallic Species

    09/2008 2nd EuCheMS Chemistry Congress, Torino, Italy, poster presentation:

    Nucleophilic Reactivities of Wittig Ylides and Phosphoryl-Stabilized

    Carbanions

    02/2009 International Symposium on Modern Organic Chemistry, Monastir, Tunesia,

    oral- and poster presentation: Nucleophilicity Parameters for Phosphoryl-

    Stabilized Carbanions and Phosphorus Ylides: Implications for Wittig and

    Related Olefination Reactions

    03/2009 Synthesefest, Munich, Germany, poster presentation: Nucleophilicity

    Parameters for Phosphoryl-Stabilized Carbanions and Phosphorus Ylides:

    Implications for Wittig and Related Olefination Reactions

    03/2010 International Meeting of the Sonderforschungsbereich 749, Kloster Irsee,

    Germany, oral- and poster presentation: Nucleophilicity Parameters for Sulfur

    Ylides: Reference Compounds for Elucidating the Ambident Reactivities of ,-

    Unsaturated Carbonyl Compounds and Imines

    07/2010 9th International Symposium on Carbanion Chemistry, Florence, Italy, oral

    presentation: Nucleophilic Reactivites of Sulfur Ylides and Related Carbanions:

    Comparison with Structurally Related Organophosphorus Compounds

  • Table of Contents

    Table of Contents

    Chapter 1: Summary 1

    Chapter 2: Introduction 19

    Chapter 3: Nucleophilicity Parameters for Phosphoryl-Stabilized Carbanions and Phosphorus Ylides: Implications for Wittig and Related Olefination Reactions

    27

    Chapter 4: Nucleophilic Reactivities of Sulfur Ylides and Related Carbanions: Comparison with Structurally Related Organophosphorus Compounds

    93

    Chapter 5: Scope and Limitations of Cyclopropanations with Sulfur Ylides 129

    Chapter 6: How Does Electrostatic Activation Control Iminium Catalyzed Cyclopropanations?

    187

    Chapter 7: Quantification of the Electrophilic Reactivities of Aldehydes, Imines, and Enones

    201

    Chapter 8: Ambident Electrophilicity of a Cinnamaldehyde-Derived Imine 271

    Chapter 9: Nucleophilicities of the Anions of Arylacetonitriles and Arylpropionitriles in Dimethyl Sulfoxide

    311

    Chapter 10: Nucleophilic Reactivities of Alkali Cyclopentadienides (CpK, CpNa, CpLi)

    347

  • Chapter 1: Summary

    1

    Chapter 1: Summary 1 General

    Many organic reactions can be classified as nucleophile-electrophile combinations, the rates

    of which can be described by eq 1, where k20C is the second-order rate constant in M1 s1, s is

    a nucleophile-specific slope parameter, N is a nucleophilicity parameter, and E is an

    electrophilicity parameter.

    log k20C = s(N + E) (1)

    Based on this correlation equation, the reactivities of many different classes of nucleophiles

    have already been quantified and compared. On the contrary, only a rather limited amount of

    electrophiles including carbocations, benzhydrylium ions, cationic metal -complexes, and

    electron-deficient Michael acceptors have so far been characterized according to their

    electrophilicity E. In spite of their general importance in organic synthesis, E parameters have

    neither been reported for imines nor for ordinary carbonyl compounds or enones.

    This thesis was designed to derive the nucleophilic reactivities of phosphorus- and sulfur

    ylides as well as those of related carbanions in order to systematically investigate their

    reactions with carbonyl compounds, imines, and Michael acceptors. In this way, the

    quantification of the reactivity of these important electrophilies shou