This dissertation describes research that delves into exploring puzzling chemical phenomena utilizing modern computational chemistry methods. Theoretical chemical models that are coupled with quantum mechanical (QM) calculations can dissect complex chemical reactions into many components that influence chemical reactivity and selectivity. Each chapter of this dissertation demonstrates that QM calculations can help predict and explain the complexities of chemical phenomena involving reaction mechanisms.

The first section (hapters 1 thru 4) details computational explorations of reactivities and selectivities of pericyclic reactions. Pericyclic reactions are an important class of chemical reactions wherein the reacting species form a cyclic transition state with aromatic delocalization. Often these reactions occur with high degrees of regio- and stereoselectivity. Chapter 1 explores the large differences in reactivity between cyclic 1- and 2-azadienes in Diels-Alder reactions. Chapter 2 investigates how thiol addition to substituted oxanorbornadienes promotes a retro-Diels-Alder reaction, as well as how the substitution pattern on the norbornadiene affects the rates of fragmentation. Chapter 3 probes how an anion-accelerated Cope rearrangement is inherently stereoselective. Chapter 4 explores if the enzyme iridoid synthase is a natural Diels-Alderase by modeling the uncatalyzed Diels-Alder reaction and determining if the background reaction is achievable and inherently stereoselective.

The second section, Chapter 5, delves into utilizing QM calculations to predict the potential reactivity of a proposed catalyst to selectivity perform anti-Markovnikov hydrations of olefins. Our calculations predict that the proposed di-manganese catalyst would produce the anti-Markovnikov product preferentially to the Markovnikov product at a ratio as low as 12:1 and as high as 100:1 depending on the catalyst ligands.

The third section (Chapters 6 and 7) tackle the stereoselectivity of chemical reactions involving nucleophilic additions to aldehydes and imines. Chapter 6 explores the mechanism and origins of the diastereoselectivity of cross-benzoin reactions of furfural and α-amino aldehydes catalyzed by a triazolium-based NHC. Chapter 7 the polar-Felkin-Anh stereoselectivity of nucleophilic addition to α-chiral imines in the presence of Lewis acid catalysts.