Leveraging Mechanistic Insight to Develop New Modes of Reactivity Between Ubiquitous Double Bond Functional Groups

Field: Chemistry (Physical Sciences)

The development of new reactivity modes within chemistry has allowed for innovations and discoveries in fields across the natural sciences. These breakthroughs have influence on everyday life by fighting diseases with pharmaceuticals and accessing new technologies with materials. The pursuit of new methods remains a goal for chemists not only to better understand the science involved but also to accelerate discoveries. This dissertation will demonstrate work on the development and application of two new reaction paradigms between commonly observed double bond functionalities: the interrupted carbonyl-olefin metathesis via oxygen atom transfer and the ruthenium alkylidene mediated metathesis of alkenes and hydrazones. Exploration of the unique mechanism of the interrupted carbonyl-olefin metathesis reaction has led to the subsequent development of two additional protocols to access indenes and cyclopentadienes. Additionally, computational investigations into the carbonyl-olefin metathesis reaction allow for better understanding of a transannular carbonyl-olefin metathesis and increased scope of the reaction to access medium sized rings via ion pair catalysts. \nIn the first report discussed, a triflic acid catalyst was employed to convert aryl ketone starting materials into tetrahydrofluorene products. This transformation was found to proceed through a transient oxetane intermediate which then undergoes an intramolecular oxygen atom transfer process. Both experimental and computational work support this new mode of reactivity as the operable pathway. This method allows a number of sterically and electronically diverse starting materials to be converted to the desired products in excellent yields. Subsequently, it was found that this new mode of reactivity, oxygen atom transfer, was not limited to aryl ketones but could also occur from cyclic and acyclic aliphatic ketones. The reports could access indene and cyclopentadiene products respectively. Computational work supports the intermediacy of an oxetane intermediate that then fragments via an elimination. \nIt was also found that the carbonyl-olefin metathesis reaction could be expanded to a transannular carbonyl-olefin metathesis reaction. However, under these conditions, three distinct products could be formed based on the Lewis acid catalyst employed. As such, significant computational effort was required to find a unifying mechanistic pathway that accounted for the formation all three products. Ultimately, an oxetane intermediate was implicated as the key species that unified the proposed mechanism. Furthermore, the use of ion pair catalysts allowed for the carbonyl-olefin metathesis reaction to be expanded to the synthesis of medium sized rings. These new superelectrophilic catalyst were found capable of cyclizing the larger ring systems. Additionally, it was found computationally that the ion pair catalysts allowed access to a new mechanistic pathway that lowered the energy of the transformation. \nLastly, the initial work towards a ruthenium alkylidene mediated metathesis of alkenes and hydrazones is discussed. This work demonstrates the first ring-closing imine-olefin metathesis reaction. Incorporation of a hydrazone or oxime into the imine functionality is proposed to reduce the polarity of the pi-bond enabling a metathesis with the robust and well-define ruthenium alkylidenes. Future work will focus on rendering the ruthenium alkylidene mediated metathesis reaction catalytic and demonstrating the utility of the method.