PROJECT SUMMARY The asymmetric formation of carbon–carbon bonds is one of the greatest challenges in organic synthesis and is an important transformation in the production of pharmaceuticals. Often, the development of these and other reactions involves empirical screening of large sets of conditions in order to arrive at an efficient transformation. Despite great progress in stereoselective organic synthesis, there remains a dearth of knowledge and generalizable models of several of the most fundamental reactions in the field. Computational chemistry has proven to be a versatile tool in the determination of mechanism and the development of new chiral catalysts. Through the use of computational methods, we will study the mechanisms and modes of stereoinduction in multiple transformations, with the goal of rationally designing new and more selective catalysts. As a results of the proposed research, I will develop a method to build on computational determination of stereoselectivity origins to predict superior asymmetric catalysts. This will lower the cost, time, and environmental impact of synthetic methodology development. Several categories of asymmetric carbon–carbon bond forming reactions will be studied computationally, including [3+2] and [4+2] cycloadditions, nickel-catalyzed reductive cyclizations, and nickel-catalyzed cross- electrophile couplings. Stereochemical models for reactions involving multiple classes of privileged chiral scaffolds, including TADDOL ligands and bidentate nitrogen ligands, will be developed. In all of these reactions, the precise identity of the catalyst has an important effect on stereochemical outcome and efficiency. By developing a model supported by a wide range of data, the results of these studies will be extrapolated further for the development of more efficient and potent synthetic methods. An understanding of the mechanisms of these reactions, as well as the unique efficiency afforded by certain catalysts, will allow for the computational prediction of more powerful and selective chiral catalysts. These catalysts will subsequently be synthesized in the laboratory and applied to a selection of synthetic reactions in order to validate their effectiveness.