ABSTRACT SYNTHETIC AND MECHANISTIC INVESTIGATIONS OF SUPERELECTROPHILIC REACTIONS Kenneth Nicholas Boblak, Ph.D. Department of Chemistry and Biochemistry Northern Illinois University, 2014 Douglas A. Klumpp, Director This dissertation describes various intramolecular cyclizations promoted by superacid. The first chapter deals with the formation of N-heterocyclic indenes. In these reactions protonated N-heterocyclic rings are shown to enhance the reactivity of the carboxonium electrophile for the cyclodehydration of various ketones. The second chapter explores an unusual regioelectronic effect that controls whether Markovnikov or conjugate addition takes place across a double bond. The addition facilitated by superacid depends on the position of olefin functionality on N-heterocyclic olefinic derivatives. The final chapter investigates highly stable superelectrophilic systems and the trapping of their carbocations to highly functionalized fluorenes. This study includes the direct observation of dicationic and tricationic reactive intermediates in magic acid media via low temperature, nuclear magnetic resonance spectroscopy. The superelectrophilic cores promote charge-charge repulsion enhancing anti-aromaticity of the polycyclic-fluorene protons. NORTHERN ILLINOIS UNIVERSITY DEKALB, ILLINOIS DECEMBER, 2014 SYNTHETIC AND MECHANISTIC INVESTIGATIONS OF SUPERELECTROPHILIC REACTIONS BY KENNETH NICHOLAS BOBLAK A DISSERTATION SUBMITTED TO THE GRADUATE SCHOOL IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE DOCTOR OF PHILOSOPHY DEPARTMENT OF CHEMISTRY AND BIOCHEMISTRY DOCTORAL DIRECTOR: Douglas A. Klumpp ACKNOWLEDGEMENTS I would like to thank my mother and father for their constant support throughout my collegiate career. My mother has always been the light in my life. My mom and dad taught me to do my best with the tools available and to never neglect the gifts within me. I am truly grateful for my sister Rebecca Boblak and my brother James Boblak, Jr. for their love and support. I would not have gotten through these years without their late night phone calls and the occasional California vacation. Thank you Jimmy and Becky, I love you both. I would also like to thank my Auntie Marilyn. All of you have always had my back and I will be forever grateful to you. Thank you for all you do for me. I would also like to thank former graduates of N.I.U., Adam Dill and Brendan Dutmer. They have been great friends over the years. In the research lab I have worked with so many wonderful chemists who taught me so much. Naredla Rajasekhar, Erum Raja, Kiran Solingapuram, and Matt O’Connor were inspirational in my development as a researcher. As an undergraduate student at Northern Illinois University I was lucky enough to start research in Professor Klumpp’s laboratory and I have worked there since the winter of 2008. I cannot say enough about my advisor. Thank you for sharing your knowledge, technique, and for being so understanding and kind over the years. I would not be the chemist I am and I certainly would never have accomplished this goal without you. Thank you. DEDICATION To my mother and father, sister and brother, and moses. V TABLE OF CONTENTS Page LIST OF FIGURES ........................................................................................................... viii LIST OF APPENDICES ..................................................................................................... ix LIST OF SCHEMES .............................................................................................................x LIST OF ABBREVIATIONS ............................................................................................. xii CHAPTER 1: INTRODUCTION .........................................................................................1 1. Superacids .....................................................................................................................1 2. Electrophiles .................................................................................................................3 3. Superelectophiles. .........................................................................................................9 CHAPTER 2: CYCLODEHYDRATION OF DIHYDROCINNAMOYL- FUNCTIONALIZED N-HETEROCYCLES TO INDENES ................................................ 12 1. Introduction ................................................................................................................. 12 2. Results and Discussion ................................................................................................. 15 3. Conclusions ................................................................................................................. 25 4. Experimental Section ................................................................................................... 26 CHAPTER 3: INTROMOLECULAR CONJUGATE AND MARKOVNIKOV ADDITIONS WITH HETEROCYCLIC OLEFINS ............................................................. 39 1. Introduction ................................................................................................................. 39 2. Results and Discussion ................................................................................................. 43 3. Conclusions ................................................................................................................. 53 4. Experimental ................................................................................................................ 54 CHAPTER 4: SUPERACID-PROMOTED CYCLODEHYDRATION TO DICATIONS AND TRICATIONS............................................................................................................ 64 1. Introduction ................................................................................................................. 64 2. Results and Discussion ................................................................................................. 68 3. Conclusions. ................................................................................................................ 84 4. Experimental. ............................................................................................................... 84 vi REFERENCES.................................................................................................................... 92 APPENDIX A ..................................................................................................................... 98 APPENDIX B ................................................................................................................... 135 APPENDIX C ................................................................................................................... 176 VII LIST OF TABLES Table Page Table 2.1: Indene and Spirocycle Examples ............................................................ 13 Table 2.2: Cyclodehydration Substrates, Products, and Yields ................................ 18 Table 2.3: Failed Cyclodehydration Reactions ........................................................ 22 Table 3.1: Superacid-Promoted Conjugate Addition Reactions ............................... 48 Table 4.1: Superacid-Promoted Reaction Products with Different Arenes ............... 72 Table 4.2: Superacid-Promoted Reaction Products with Different N-Heterocycles .. 73 VIII LIST OF FIGURES Figure Page Figure 1.1: The Hammett Acidity Scale ................................................................. 3 Figure 1.2: Stability Trends of Substituted Carbocations........................................ 4 Figure 1.3: Examples of Carbonium Ions ............................................................... 5 Figure 1.4: Model of Polar Organic Reactivity ...................................................... 6 Figure 1.5: Categories of Superelectrophiles .......................................................... 9 Figure 2.1: Cyclodehydrations (9 to 17 and 38 to 39) in TfOH at 25°C .................. 24 Figure 3.1: Cold-Temperature 13C-NMR Spectrum of Quinoxaline Dication ......... 42 Figure 3.2: Cold-Temperature 13C-NMR Spectrum of Quinoxaline Trication ........ 42 Figure 3.3: Reaction Mechanisms .......................................................................... 51 Figure 4.1: Examples of the Use of Fluorene Ring Systems in Electron Devices .... 65 Figure 4.2: Synthetic Intermediate N-Heterocyclic Ketones ................................... 69 Figure 4.3: 13C-NMR Spectrum of (12) in the Presence of Magic Acid .................. 74 Figure 4.4: 1H-NMR Spectrum of (12) in the Presence of Magic Acid ................... 75 Figure 4.5: 13C-NMR Spectra of (13) and (14) in the Presence of Magic Acid ....... 77 Figure 4.6: 1H-NMR Spectra of (13) and (14) in the Presence of Magic Acid ........ 78 Figure 4.7: 13C-NMR and 13C-NMR Spectra of 33 in the Presence of Magic Acid . 80 Figure 4.8: COSY of 33 in the Presence of Magic Acid ......................................... 81 Figure 4.9: HMQC of 33 in the Presence of Magic Acid ........................................ 82 Figure 4.10: HMBC of 33 in the Presence of Magic Acid ...................................... 83 IX LIST OF APPENDICES Appendix Page A. 1H NMR and 13C NMR Spectra of Compounds (Chapter 2) .................. 112 B. 1H NMR and 13C NMR Spectra of Compounds (Chapter 3) .................. 149 C. 1H NMR and 13C NMR Spectra of Compounds (Chapter 4) .................. 176 X LIST OF SCHEMES Scheme Page Scheme 1.1: General Grignard Reaction Mechanism ............................................