Highly Functionalized Piperidine Generation via Pyridine Repolarization and Hyper-Distorted Allyl Complexes of {TpW(NO){PMe3)} Daniel Patrick Harrison Midlothian, Virginia B.S., Virginia Military Institute, 2004 A Dissertation presented to the Graduate Faculty of the University of Virginia in Candidacy for the Degree of Doctor of Philosophy Department of Chemistry University of Virginia February, 2011 .L ii Abstract Chapter 1 introduces the traditional organic chemistry of pyridine with an emphasis on its dearomatization. Organometallic methods of dearomatization are also discussed. Strategies for averting nitrogen coordination (i.e. κN) in favor of haptotropic (i.e. η2, η4, η6) pyridine coordination are discussed, as well as known modifications of these carbon-coordinated pyridines. The work previously performed by our group with {TpW(NO)(PMe3)} and our strategy to utilize this fragment is introduced. Chapters 2 and 3 report our findings on the large scale synthesis of η2-pyridine complexes of tungsten, utilizing a borane-protection strategy to avert κN coordination. The reactivity of complexes that result from the removal of the borane and replacement with alternative electrophilic groups are investigated. In particular, we have found that an acetyl group provides an isolable N-acetylpyridinium complex, which allows for the mild regio- and stereoselective modification of the pyridine ring with nucleophiles. Chapters 4 and 5 report on the fundamentally new chemistry of pyridine that results from the coordination of the {TpW(NO)(PMe3)}. Tandem electrophilic followed by nucleophilic additions and cycloadditions with 1,2-dihydropyridine (DHP) complexes are reported. These findings suggest that the metal coordination reverses the polarization of the pyridine ring carbons such that electrophiles add α-to-N rather than β-to-N. Importantly, we report the isolation of new 2-, 3-, or 4-substitituted piperidine compounds that result from this methodology. Chapter 6 reports pyridine ring scission with nucleophiles capable of delivering 4 e- (2σ, 2π) to the pyridine ring. The resulting conjugated complexes were probed for iii fluorescent activity. While none was found for the metal complexes, photolysis liberated an organic cation that did display fluorescence. Chapter 7 discusses our discovery of highly distorted allyl complexes of {TpW(NO)(PMe3)}. Here we endeavor to understand the origin of the large distortions and orientations of allyls observed in crystal structures and reproduced by density functional theory (DFT) calculations. We propose that the nitrosyl is responsible for the distortion, while Tp is responsible for the orientation of the allyls distal to PMe3. iv Acknowledgements Sir Isaac Newton once said, “If I have seen further it is only by standing on the shoulders of giants.” This quote sums up my feeling toward my success in chemistry. While I feel as though I have contributed something to the field of chemistry, I cannot take all of credit for it. There have been many individuals who have had an integral part in my success. From the lab research perspective, any success I have had as a graduate student is a result of 2 things: 1) the outstanding cumulative efforts of my predecessors and 2) the presence of my co-workers. I am always amazed that the Harman lab research projects stemmed from W. Dean Harman’s characterization of some odd CV signals. He has taken his initial physical inorganic investigations and done what most organometallic chemists desire to do: expand the methodology to something more generally relevant than the initial discovery. Unfortunately, the potential of this work has not yet been realized by the broader chemical community. However this may soon change as Sigma-Aldrich has recently agreed to supply starting materials of the tungsten system. These chemicals will then undergo testing to determine their medicinal capabilities. I have always considered myself fortunate to work for Dean for many reasons. For example, I knew the moment that I visited the UVa Chemistry department that I wanted to work for Dean because 1) I realized that his entire purpose is to nurture and teach, and therefore would be patient with my sometimes “schizophrenic” thoughts and ideas and 2) because the fundamental dπ-pπ interaction that Dean drew at that first v meeting captivated me. During the past five years, he has proven to be incredibly nurturing and caring and spent countless hours teaching and answering my questions that will help serve me forevermore. Not to mention, Dean has always gone to bat for us whenever we needed him too. Dean has a laissez-faire philosophy when it comes to graduate students and research. That is, Dean believes that we are here to make our Ph.D. what we want it to be and that he is here as a consultant. Although frustrating at times, this philosophy has allowed me to develop as a critical thinker and take responsibility for the evolution of my project, including both its successes and failures. I hope to be able to follow his example in my in my future projects. One thing that I have learned about Dean is that he when he gives one criticism he always has pure intentions. Seemingly contradictorily, he has been willing to be completely and utterly honest with me in order to help me achieve my goals. Overall, I am very thankful Dean took a chance on me and allowed me to work in his lab. Everything he has done for me has really paid off and I cannot thank him enough for all of his effort. Summers in the Harman lab would not be complete without the presence of our favorite University of Richmond professor, Bill Myers. It has been a riot getting to know him. I never tire of hearing his stories, even though I have heard many of them four or five times. His quirky sense of humor is refreshing and his kindness is rivaled only by Dean. Bill has an uncanny ability to patiently analyze 2D NMR spectra and has helped shape the way we characterize and think about multidimensional spectra. As a result he as developed clever naming schemes of PzA, PzB, and PzC of the Tp ligand. His vi willingness to assist with the collection of 2D NMR and HRMS data has been instrumental to my ability to quickly write numerous papers, as his instruments are outstanding and allow for the rapid analysis of compounds. I consider Bill a good friend and colleague and I treasure the time that we had together. One of the neat things that Bill does for the group is to bring new undergraduate students to our lab each summer. I have enjoyed meeting them, developing friendships with them, and taking part in their chemical training. Most notably, I have enjoyed working with Diana Iovan and Dalsher Nagra as they have each brought specific attributes to our lab. Diana is responsible for setting up many NMR experiments and HRMS data collection. It is clear that Diana will go far with her intelligence and willingness to work incredibly hard. Dalsher is one of the most charismatic individuals I have ever met. His willingness to ask questions will allow help him in his future endeavors. Predecessors: Although I spent varying amounts of time with others in lab, each and every person has enhanced my education, either scientific or otherwise, and as a result I consider myself a better person. Ed Lis was my initial graduate mentor who taught me for the first six months. He taught me about quinolone and how he had achieved certain laboratory tasks (e.g. precipitations, glovebox transfers, etc.). When I first arrived, Kim Bassett was the mother figure of the lab. She taught me how to be considerate in a laboratory setting, a skill that has served me well for the last five years by allowing me to maintain positive vii interpersonal relationships. Becky Salomon and I attended many classes and went through candidacy together. Toward the end of her graduate career, good fortune shined on her and allowed her to capitalize on the properties of the tungsten system by trapping a much sought after aniline complex with acid. After its initial discovery, she successfully showed its utility by successfully extrapolating most of the reaction classes that have been found to work with the phenol complex to the anilinium complex. George Kosturko always impressed me with his hard work, and as a result helped me set a standard for how much time I spent in the lab. We worked in adjacent ports and our close proximity allowed for many conversations about possible reactions to try with our complexes, life, etc. One of the most important things that George taught me was the importance of networking and keeping good inter-lab relationships healthy. If I am not mistaken, he was a key player in implementing the sharing of chemicals and resources between labs. Our ability to swap chemicals with other labs has been instrumental when we have tried to discover new reaction classes while still trying to save money. Mike Todd and I shared Box 1 for all but about six months during his time at the lab. Mike is in general a quiet person whose intelligence was often revealed during our lunchtime conversations. I appreciate his time and patience while acclimating me to Box 1, transferring the vacuum pump job to me, and his willingness to allow me to bounce ideas off of him. One somewhat funny thing that Mike did not know while he was here was that during my early days at group meetings, when I did not understand anything viii anyone was saying, I found refuge in counting the number of times Mike said “umm” (one time I stopped counting after 10 minutes when he hit ~112)! When I reflect back on who I would consider most crucial to my laboratory and mental training, Kevin Welch is that person.