UC Davis

This dissertation is a collection of computational chemistry works on chemical and photochemical reaction mechanisms. Multiple theoretical tools have been utilized to tackle mechanistic questions in organic chemistry and photochemistry. They include density functional theory, machine learning and ab initio molecular dynamics and they are briefly discussed in chapter 1.Chapter 2 is about the migratory aptitude of carbocation rearrangement from the perspective of dynamic effects. Carbocation rearrangement reactions are of great significance to synthetic and biosynthetic chemistry. In pursuit of a scale of inherent migratory aptitude that takes into account dynamic effects, both uphill and downhill ab initio molecular dynamics (AIMD) simulations were used to examine competing migration events in a model system designed to remove steric and electronic biases. The results of these simulations were combined with detailed investigations of potential energy surface topography and variational transition state theory calculations to reveal the importance of non-statistical dynamic effects on migratory aptitude. Chapter 2 formulates a selectivity model based on the widths of pathways to competing products, rather than barrier heights, for a butadiene + allyl cation reaction. This model was arrived at via analysis of stationary points, intrinsic reaction coordinates, potential energy surface shapes and direct dynamics trajectories, all determined using quantum chemical methods. Chapter 3 is on photochemistry. Selectivity for photochemical reactions where crossing between excited state and ground state surfaces occurs near ground state transition structures that interconvert competing products should be controlled by the momentum of the reacting molecules as they return to the ground state and the shape of the potential energy surfaces involved. The roles of these factors are revealed here for a classic photochemical reaction: deazetization of 2,3-diazabicyclo[2.2.2]oct-2-ene. The utility of analogies between such photochemical reactions and ground state reactions with post-transition state bifurcations for forward design is suggested. Chapter 4 is a collaborative project with the Sarpong group at UC Berkley. They have made synthetic efforts towards the pupukeanane natural products. The 10-step enantiospecific synthetic route to 2-isocyanoallopupukeanane facilitates an unprecedented bio-inspired ‘contra-biosynthetic’ rearrangement, providing divergent access to the pupukeanane core. The computational studies provide insights into the nature of this novel rearrangement. Chapter 5 is a collaborative project with the Zheng group at the University of Arkansas. Distonic radical cations generated from the ring-opening of cyclopropylamines have shown distinct reactivities and TMSCN has been shown to be able to make the ring-opening happen. Our computational study has pointed out that the change in the photoredox potential and the quenching of the distonic radical cations by TMSCN are critical to the reactivities. Chapter 6 is a collaborative project with the Lectka group at Johns Hopkins University on a through-space arene activations with halogens, tetrazoles and achiral esters and amides. Contrary to previously assumed direct activation through σ-complex stabilization, computational and experimental results suggest that these reactions proceed by a relay mechanism wherein the lone pair-containing activators form exothermic π-complexes with electrophilic nitronium ion before transferring it to the probe ring through low barrier transition states.