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Reactions of Carbanions with Michael Acceptors and Electron-Deficient Arenes: Quantifying Polar Organic Reactivity

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Reactions of Carbanions with Michael Acceptors and Electron-Deficient Arenes: Quantifying Polar Organic Reactivity Dissertation zur Erlangung des Doktorgrades der Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-Universität München Reactions of Carbanions with Michael Acceptors and Electron-deficient Arenes: Quantifying Polar Organic Reactivity Dipl. Chem. Florian Seeliger aus Hamburg 2008 Erklärung Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29. Januar 1998 von Herrn Prof. Dr. Herbert Mayr betreut. Ehrenwörtliche Versicherung Diese Dissertation wurde selbständig und ohne unerlaubte Hilfe erarbeitet. München, 13.03.2008 ……..…………………………... Florian Seeliger Dissertation eingereicht am 13.03.2008 1.Gutachter Prof. Dr. Herbert Mayr 2.Gutachter Prof. Dr. Hendrik Zipse Mündliche Prüfung am 24.04.2008 Für Birgit Danksagung Ich möchte mich an dieser Stelle ganz herzlich bei Herrn Prof. Dr. Herbert Mayr für seine herausragende und beispielhafte Betreuung während der Durchführung meiner Arbeit, die interessante Themenstellung und seine stete Hilfs- und Diskussionsbereitschaft bedanken. Weiterhin gilt mein Dank Herrn Prof. Dr. Mieczyslaw Makosza, der es mir ermöglichte, für 2 Monate in Warschau zu forschen und Prof. Dr. Hendrik Zipse, der mir als Ratgeber für die quantenchemischen Rechnungen hilfreich zur Seite stand. Den Mitgliedern des Arbeitskreises danke ich für ein äußerst angenehmes Arbeitsklima mit vielen abwechslungsreichen Diskussionen über Chemie und andere Dinge. Meinen Laborkollegen Oliver Kaumanns, Heike Schaller, Markus Horn und Erik Breuer sei für ihre Hilfsbereitschaft und das tolle Arbeitsklima besonders gedankt. Es war eine sehr schöne Zeit! Ferner möchte ich mich bedanken bei Sylwia Blazej, die mir in meiner Zeit in Warschau hilfreich zur Seite stand. Meinen F-Praktikanten, Barbara Körner, Florian Hofbauer und Sebastian Bernhard danke ich für ihren großen Einsatz bei der Durchführung der experimentellen Arbeiten und die humorvolle Zusammenarbeit und wünsche ihnen für ihre Zukunft alles Gute! Für die kritische und zügige Durchsicht dieser Arbeit danke ich Nicolas Streidl, Markus Horn, Dorothea Richter, Roland Appel, Tobias Nigst, Martin Breugst und Barbara Seeliger. Zuletzt danke ich aber vor allem meiner Familie, insbesondere meiner Mutter und meinem Vater, die mich nicht nur während meiner Promotion, sondern Zeit meines Lebens unterstützt haben. Publikationen (1) S. T. A. Berger, F. H. Seeliger, F. Hofbauer, H. Mayr, Org. Biomol. Chem. 2007, 5, 3020-3026: ”Electrophilicity Parameters for 2-Benzylidene-indan-1,3-diones - a systematic extension of the benzhydrylium based electrophilicity scale” (2) F. Seeliger, S. T. A. Berger, G. Y. Remennikov, K. Polborn, H. Mayr, J. Org. Chem. 2007, 72, 9170-9180: ”Electrophilicity of 5-Benzylidene-1,3-dimethyl-barbituric and – thiobarbituric Acids” (3) F. Seeliger, S. Blazej, S. Bernhardt, H. Mayr, M. Makosza, Chem. Eur. J. 2008, accepted.: ” Reactivity of Nitro-(hetero)arenes with Carbanions: Bridging Aromatic, Heteroaromatic, and Vinylic Electrophilicity” (4) F. Seeliger, H. Mayr, Org. Biomol. Chem. 2008, submitted: “Nucleophilic Behavior of Sulfonyl-stabilized Carbanions” Konferenzbeiträge (1) 08/2006 18. IUPAC Konferenz „Physical Organic Chemistry“, Warschau, Polen Vortrag: „Quantifying Electrophilicity and Nucleophilicity“ Poster Präsentation: “Electrophilicities of Benzylidenebarbituric Acids” Table of Contents 0 SUMMARY ............................................................................................................... 1 0.1 INTRODUCTION ................................................................................................................. 1 0.2 ELECTROPHILICITY OF 5-BENZYLIDENE-1,3-DIMETHYL-BARBITURIC AND -THIOBARBITURIC ACIDS.................................................................................................. 1 0.3 ELECTROPHILICITIES OF 2-BENZYLIDENE-INDAN-1,3-DIONES .......................................... 3 0.4 REACTIONS OF NITRO(HETERO)ARENES WITH CARBANIONS − BRIDGING AROMATIC, HETEROAROMATIC, AND VINYLIC ELECTROPHILICITY...................................................... 4 0.5 NUCLEOPHILIC BEHAVIOR OF SULFONYL-STABILIZED CARBANIONS................................ 6 0.6 SOLVENT EFFECTS ON THE RATES OF ELECTROPHILE-NUCLEOPHILE COMBINATIONS...... 8 0.7 MISCELLANEOUS EXPERIMENTS ....................................................................................... 9 0.7.1 Combinatorial Kinetics.......................................................................................................... 9 0.7.2 The Reactivity of the 2-(p-Nitrophenyl)-propionitrile Anion............................................... 10 1 INTRODUCTION AND OBJECTIVES .............................................................. 11 1.1 INTRODUCTION ............................................................................................................... 11 1.2 OBJECTIVES .................................................................................................................... 12 1.3 REFERENCES ................................................................................................................... 13 2 ELECTROPHILICITY OF 5-BENZYLIDENE-1,3-DIMETHYL- BARBITURIC AND -THIOBARBITURIC ACIDS ........................................... 15 2.1 INTRODUCTION ............................................................................................................... 15 2.2 RESULTS ......................................................................................................................... 17 2.2.1 Product Studies.................................................................................................................... 17 2.2.2 Kinetics................................................................................................................................ 21 2.3 DISCUSSION .................................................................................................................... 24 2.3.1 Reactions with Carbanions.................................................................................................. 24 2.3.2 Reactions with other Types of Nucleophiles........................................................................ 27 2.4 CONCLUSION .................................................................................................................. 32 2.5 EXPERIMENTAL SECTION ................................................................................................ 32 2.5.1 General Comments .............................................................................................................. 32 2.5.2 Synthesis of 5-Benzylidene-1,3-dimethyl(thio)barbituric Acids .......................................... 33 2.5.3 Characterization of Potassium Salts 3 by NMR Spectroscopy............................................ 33 2.5.4 Synthesis of Products 5........................................................................................................ 35 2.5.5 Kinetic Experiments............................................................................................................. 37 2.6 REFERENCES ................................................................................................................... 54 3 ELECTROPHILICITY PARAMETERS FOR 2-BENZYLIDENE-INDAN-1,3- DIONES − A SYSTEMATIC EXTENSION OF THE BENZHYDRYLIUM BASED ELECTROPHILICITY SCALE............................................................. 58 3.1 INTRODUCTION ............................................................................................................... 58 3.2 RESULTS AND DISCUSSION ............................................................................................. 61 3.2.1 Preparation of the Electrophiles 1a-d ................................................................................. 61 3.2.2 Reaction Products................................................................................................................ 61 3.2.3 Kinetic Investigations in DMSO .......................................................................................... 62 3.2.4 Correlation Analysis............................................................................................................ 64 3.3 CONCLUSION .................................................................................................................. 72 3.4 EXPERIMENTAL SECTION ................................................................................................ 72 3.4.1 General Comments .............................................................................................................. 72 I 3.4.2 Products of the Reactions of 2-Benzylidene-indan-1,3-dione (1) with Carbanions 2 ......... 73 3.4.3 Kinetic Experiments............................................................................................................. 76 3.5 REFERENCES ................................................................................................................... 81 4 REACTIONS OF NITRO(HETERO)ARENES WITH CARBANIONS: BRIDGING AROMATIC, HETEROAROMATIC, AND VINYLIC ELECTROPHILICITY ......................................................................................... 84 4.1 INTRODUCTION ............................................................................................................... 84 4.2 RESULTS ......................................................................................................................... 86 4.2.1 Synthesis of the Reactants...................................................................................................
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