The Generation and Reactivity of Vinyl Carbocations
This dissertation describes efforts to generate vinyl carbocation intermediates to leveragetheir high–reactivity, with a particular focus on subsequent C–H insertion reactions to forge new C–C bonds. These intermediates have historically been difficult to generate using catalytic regimes, but in doing so their reactivity can be controlled to give high-yielding methodologies. Additionally, efforts to search for new means to generate these intermediates often leads to discovery of novel reactivity. A variety of conditions have been developed to generate these intermediates that will be highlighted in five chapters of this thesis. An initial overview will be given to demonstrate how access to vinyl carbocations has steadily increased in the past decades, allowing for discovery of novel reactivity particularly highlighted by C–H functionalization. Then, efforts of my colleagues and myself are partitioned into four main categories related to the generation of vinyl carbocations and their subsequent reactivity. In the first chapter current state-of-the-art and previous methods of vinyl carbocation generation are reviewed to shed light on the massive amount of work already dedicated to producing these reactive intermediates. The second and third chapters cover the development of Br�nsted basic conditions to generate these intermediates. These chapters detail the surprising discovery of utilizing lithium hexamethyl disilazide, a strong base, to generate vinyl carbocations that subsequently undergo C–H insertion reactions to yield olefinic products. These chapters will describe how these new basic conditions allowed for heteroatom containing substrates and additionally allowed for the use of much more easily accessible urea catalysts. The fourth chapter describes electrochemical means to gain access to these intermediates primarily for nucleophilic fluorination to produce fluoro-olefins. This work was a direct result of the annoyance in needing to use strong Lewis acids; while still allowing fairly diverse substrates, these conditions drastically limited the types of reagents that could be utilized and overall limited the methodology. Instead, Lewis-acid free conditions utilizing electrodes to oxidize substrates to the vinyl carbocation intermediate were developed. Finally, the fifth chapter details ongoing efforts to generate vinyl carbocations paired with chiral counterions to yield enantioselective C–H insertion reactions as well as the future outlook on other issues to tackle in developing new methodology. This work required small incremental discoveries in both catalyst and substrate design, and in all it took four PhD students almost two years to gain high levels of enantio- and regio- selectivity.