The studies reported in this dissertation illustrate a few selected examples of using density functional theory (DFT) calculations to investigate various aspects of iridium-catalyzed reactions and ring-opening of bicyclic cyclobutene rings. These computational predictions not only reproduce and explain experimental results and offer insights to reaction mechanisms, but also provide theoretical models to predict reactivity, regio- and stereoselectivities.

Chapter 1 is a review surveying the literature of iridium-catalyzed borylation reactions. Emphasis is placed on iridium-catalyzed borylation of alkenes and arenes. In particular, I discuss the history leading up to the current catalyst systems for iridium-catalyzed borylation reactions, and regioselectivity of borylation for a number of different substrates. Despite the large amount of work on iridium-catalyzed borylation reactions, this review shows that there is still much to be understood regarding the origins of observed regioselectivities.

Chapters 2 and 3 describe theoretical investigations of Ir(III)-catalyzed borylation reactions. The origins of regioselectivities observed in the borylation of pyridine are discussed in Chapter 2. The high selectivity for borylation at the 3- and 4- position of pyridine is attributed to the formation of a Lewis acid-base complex between pyridine and either boron species or iridium species in solution. The origins of regioselectivities for the iridium-catalyzed borylation of substituted arenes and 5-membered heterocycles are discussed in Chapter 3. The distortion/interaction model was employed to understand the origins of the selectivities in these reactions. Computations revealed that regioselectivity is mainly controlled by differences in the interaction energies between the iridium catalyst and arene carbon.

Chapter 4 illustrates a theoretical study of ring-opening in strained, trans-substituted cyclobutenes. The torquoselectively preferred outward ring-opening products are unable to form due to ring strain inherent in 9- and 10-membered macrocyclic (E,E)-1,3-dienes. As a result of this study, I propose a general methodology for stereoselective synthesis of macrocyclic (Z,Z)-1,3-dienes termed strain-induced thermal selectivity (SITS).