Phosphorus Ylides, Sulfur Ylides, and Related Carbanions as Reference Nucleophiles for the

375 Pages·2011·3.09 MB·English

by  Roland Appel

Dissertation zur Erlangung des Doktorgrades
der Fakultät für Chemie und Pharmazie
der Ludwig-Maximilians-Universität München

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 München

2011
Erklärung

Diese Dissertation wurde im Sinne von §13 Abs. 3 bzw. 4 der Promotionsordnung vom 29.
Januar 1998 (in der Fassung der vierten Änderungssatzung vom 26. November 2004) von
Herrn Professor Dr. Herbert Mayr betreut.

Ehrenwörtliche Versicherung

Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe erarbeitet.

München, 10.02.2011

____________________________
Roland Appel

Dissertation eingereicht am: 10.02.2011

1.Gutachter: Prof. Dr. Herbert Mayr
2.Gutachter: Prof. Dr. Manfred Heuschmann

Mündliche Prüfung am: 05.04.2011
FÜR 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 Allgäuer, 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 α,β-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 α,β-
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 27
Carbanions and Phosphorus Ylides: Implications for Wittig and
Related Olefination Reactions

Chapter 4: Nucleophilic Reactivities of Sulfur Ylides and Related 93
Carbanions: Comparison with Structurally Related
Organophosphorus Compounds

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

Chapter 6: How Does Electrostatic Activation Control Iminium Catalyzed 187
Cyclopropanations?

Chapter 7: Quantification of the Electrophilic Reactivities of Aldehydes, 201
Imines, and Enones

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

Chapter 9: Nucleophilicities of the Anions of Arylacetonitriles and 311
Arylpropionitriles in Dimethyl Sulfoxide

Chapter 10: Nucleophilic Reactivities of Alkali Cyclopentadienides 347
(CpK, CpNa, CpLi)
Chapter 1: Summary
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 k is the second-order rate constant in M–1 s–1, s is
20°C
a nucleophile-specific slope parameter, N is a nucleophilicity parameter, and E is an
electrophilicity parameter.

log k = s(N + E) (1)
20°C

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 should be achieved.
Furthermore, the nucleophilic reactivities of stabilized carbanions and their dependence on the
alkali counterion should be investigated in order to elucidate the dependence of the
nucleophilicity on the corresponding counterion.

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

Kinetics for the reactions of four phosphoryl-stabilized carbanions and of four phosphorus
ylides with benzhydrylium ions and structurally related quinone methides as well as with
various substituted benzaldehydes have been determined by UV-Vis spectroscopy. While the
reactions with carbocations and Michael acceptors yielded simple addition products, the well-
known Wittig-type olefination products were obtained in the reactions with benzaldehydes
(Scheme 1).
1
Chapter 1: Summary
Scheme 1: Reactions of Phosphoryl-Stabilized Carbanions and Phosphorus Ylides with
Benzhydrylium Ions, Quinone Methides, and Benzaldehydes.

The obtained second-order rate constants (log k ) correlated linearly with the electrophilicity
2
parameters E of the employed benzhydrylium ions and Michael acceptors as required by eq 1,
which allowed us to calculate the nucleophile-specific parameters N and s for phosphoryl-
substituted carbanions and phosphorus ylides (Figure 1).
7
6
5
4
3
2
1
0
-1
-20 -18 -16 -14 -12 -10 -8 -6 -4 -2

Figure 1: Plots of log k for the reactions of phosphonate-stabilized carbanions and
2
phosphorus ylides with benzhydrylium ions and quinone methides at 20°C versus their
electrophilicity parameters E (filled symbols denote reactions in DMSO, open symbols
reactions in CH Cl ).
2 2
2