Studies on the Photochemistry of Crystalline, Organic Molecules as a Green, Highly-Selective Synthetic Methodology
Solid-state photochemistry constitutes a promising, yet underutilized, method to construct challenging carbon–carbon bonds featured in strained and sterically-encumbered structural motifs. This dissertation describes studies on leveraging the crystalline solid-state to impart high levels of chemical control over photochemical reactions aimed at the construction of complex molecules. Specifically, the stereospecific syntheses of functionalized vicinal quaternary stereocenters and sterically-congested cyclopropanes via this methodology are detailed. The regiocontrolled addition of reverse prenyl radical fragments is also described. Chapter One presents an overview of solid-state photochemistry and the considerations which must be made in engineering such reactions. This includes a description of early studies that form the foundation for thermochemical and structural parameters for successful crystalline molecules. The application to and promise in synthetic endeavors is discussed in the form of scalability and recent total syntheses of complex molecules of interest. Chapter Two details the synthesis and solid-state photodecarbonylation of a crystalline, hexasubstituted ketone wherein the six ⍺-substituents are unique. This ketone represents one of the most complex our group has studied to date that effectively leverages the crystalline lattice to selectively construct the synthetically-daunting vicinal quaternary stereocenter motif. This work showcases the potential this methodology holds in constructing “building block” compounds that could be employed in diversity-oriented synthesis-focused projects. Chapter Three focuses on the solid-state photodenitrogenation of a set of adamantyl-1-pyrazolines to stereospecifically synthesize sterically-congested cyclopropanes. The targeted cyclopropanes similarly feature the vicinal quaternary stereocenter motif, underscoring the promise of this approach in accessing highly-strained synthons. Additionally, these pyrazolines undergo rare, solid-state thermal denitrogenations in a highly stereospecific manner, highlighting the potential for well-engineered crystalline compounds to undergo similar reactions. Chapter Four discusses a proof-of-concept study centered on the aspect of solid-state regiocontrol. Crystalline reverse prenyl ketones were shown to effectively decarbonylate and afford the regioretentive reverse prenyl photoproducts with greater selectivity compared to the solution-phase reactions. Given the prevalence of prenyl, reverse prenyl, and other unsymmetrical allyl-type fragments in terpenes and other natural products, this approach could develop into an effective strategy-level reaction to install such moieties in a regioselective manner.