Computational Investigations of Transition Metal Catalyzed Reaction Mechanisms and the Verification of Q2MM Predictions

The computational chemistry community has long sought to develop predictive methods to accelerate experimental studies. Understanding chemical transformations is a critical step in downstream applications and studies of any given reaction including the development of complimentary methodologies. The development of predictive methods in organic chemistry heavily relies on a thorough understanding of mechanism. This is especially true when predicting stereoselectivity of a given reaction, where properly identifying the stereodetermining step is crucial, otherwise the model’s accuracy will suffer, ultimately leaving predictions unreliable. The Quantum Guided Molecular Mechanics (Q2MM) method allows for the development of transition state force field (TSFF) parameters that can be utilized in the prediction of stereoisomer ratios. This method relies on understanding the stereodetermining step for the reaction of interest and allows one to quickly screen chiral ligand libraries, identifying the highest performing ligand for the transformation. This thesis describes the Density Functional Theory (DFT) study of 3 reaction mechanisms, whereby the first investigates the Ni-catalyzed conjugate addition of trialkylboranes to α,β – unsaturated esters. The proposed intramolecular transmetalation proved to be energetically infeasible, leading to alternative transmetalation pathways being examined. The second study focused on the mechanistic differences between the underlying vinyl cyclopropane rearrangement in vinyl isocyanates and vinyl ketenes. The third study sought to understand the observed alkene regioselectivity in the [3+1]-cycloaddition of Pd-carbenoids and trimethylene methane reagents. Additionally, the experimental verification of Q2MM predictions for the Pd- 1,4-addition of aryl boronic acids and cyclic enones is presented here, where predictions pointed towards a group of ligands that could flip the observed stereoselectivity while retaining the stereochemistry of the ligand. Lastly, progress towards the development of a TSFF describing the Ir-catalyzed hydroamination of unactivated alkenes is described.