Treffer: Computational predictions and reactivity analyses of organic reactions

This thesis focuses on computational reactivity analyses and predictions for organic systems. The research began with studies on specific reactions using quantum mechanics and molecular mechanics simulations. Beyond looking at individual reactions, projects in method development were also initiated to set up a more efficient and automated procedure for tackling the challenges of exploring the conformational space, investigating the effect of reaction dynamics and suggesting possible reaction pathways. Chapter 2 focuses on the selective pyridination of 5-methylcytosine. A new reaction mechanism that aligns with the experimental result was proposed. The variations in percentage yield upon changes in the substituent in the pyridine substrate can be explained by considering the thermodynamics and kinetics of the proton transfer step from cationic 5mdC•+ to neutral pyridine substrates. Substrates with an electron-withdrawing group are disfavoured thermodynamically, while substrates with an electron-donating group face a high kinetic barrier in a key proton transfer step. Chapter 3 gives insights into the origin of enantioselectivity in 1,4-dicarbonyl synthesis reactions with diarylprolinol silyl ether catalysts via a radical pathway. A robust procedure has been developed for computational investigations of large and flexible chemical systems based on the conformation labelling system, ONIOM calculations and Python scripting. The change in enantiomeric excess due to variations in the catalyst can be explained based on conformational changes and structural deformations. In the enantioselectivity-determining radical addition step, the iminium in the lowest energy SR transition state (TS) takes up the conformation of the lowest energy ground state iminium (EE). The conjugated iminium in the SS TS adopts an EZ conformation to avoid potential structural deformations due to radical attacks from the more sterically hindered position. For systems with simpler catalysts, the imini
Krishnan-Ang Studentship for Overseas Students in the Natural Sciences Trinity College Final Term Funding