Understanding Organic Reaction Mechanisms Through Applications of Density-Functional Theory

Abstract

The application of computational chemistry has a wide scope of utility. From large systems such as proteins or metal-organic frameworks down to the understanding of individual bonding patterns between atoms, there are endless opportunities to explore. Further utility is gained when the insights and resources of computational chemists can be applied to systems under investigation by experimental chemists The combined information of computational details with experimental findings can lead to new understanding of the systems being investigated. The ring-opening transesterification polymerization of caprolactone with an aluminum- salen catalyst is a useful reaction for the conversion of caprolactone to polyester. Mechanistic understanding of this reaction was gained through the interrogation of this process with density functional theory. Further, the origins for rate-enhancement through modification of electron-withdrawing groups was explained through the analysis of partial atomic charges. A rate enhancement observed by altering the backbone of the catalyst was also explained through the development of a distortion framework analysis. Rieske oxygenase are a class of protein that executes a variety of chemical reactions such as oxygenations, O- and N-demethylations, oxidations, and C–C bond formations en route to the formation of medically relevant natural products. The continued elucidation of the mechanism, including the characterization of reactive species was persued. Computational work to understand the impact partial atomic charge on the aromatic system (by inclusion of fluorine substituents) had on the rate constant demonstrated a clear correlation between the partial atomic charge on the C(2) position and the rate constant for a variety of substrates. A new reaction, the hexadehydro-Diels–Alder (HDDA) reaction takes a diyne and a diynophile to create a reactive benzyne intermediate. A series of six intramolecular HDDA substrates were found to undergo this transformation at relatively similar rates. Analysis of transition state geometries, investigation of both closed-shell and diradical mechanistic pathways, as well as insight from high-level calculations provide information about the nature of this intramolecular reaction. Extension of the mechanism led to predictive capability in good agreement with a new set of substrates as well.