Selective transformations in chemical processes play an essential role in achieving sustainability, especially in developing energy-, cost-, and atom-efficient processes and obtaining clean energy. A highly selective catalyst is needed to achieve a selective chemical transformation. In this thesis, in an effort to achieve highly selective catalysts, we tune the catalytic microenvironment in two important chemical reactions; i.e. the nucleophilic ring-opening of trans-2,3-disubstitued epoxides, and the electroreduction of carbon dioxide to hydrocarbons. The understanding enabled by these studies reveals design principles for the development of selective catalysts and provides further insights into the reaction mechanism of existing catalysts. To demonstrate how tuning catalytic microenvironment can increase the selectivity of chemical transformation, in the first study, we present a mechanism-inspired catalyst design for epoxide transformation to _-amino alcohol, an important building block in natural product synthesis and pharmaceuticals. We demonstrate that we can achieve a selective transformation by tuning the catalyst’s first and second coordination sphere, ultimately, allowing for the development of a highly regioselective general methodology for nucleophilic ring-opening of trans-2,3-disubstituted epoxides. In an effort to accurately evaluate how tuning catalytic microenvironment control the selectivity of electrochemical CO2 reduction, in the second study, we identify factors that affect the measured performance of electrocatalysts that involve organic materials in CO2 reduction reaction and propose standard protocols to improve the accuracy and precision of the reported data. We present several experiments necessary to ensure that the observed CO2 reduction performance is from the electrocatalyst catalyzes the reduction of CO2 molecules instead of potential side reactions. We show that standardizing the measurement and reporting protocols will facilitate the development of highly selective and active electrocatalysts. To understand the effect of confined reaction space in controlling the selectivity in electrochemical CO2 reduction, in the third study, we report design strategies for the synthesis of novel electrocatalysts for carbon dioxide reduction, where we demonstrate that the confined reaction space enables changes in reaction selectivity and can impart atypical catalytic capabilities to metals that are not otherwise active for CO2R. We utilize metal-organic frameworks (MOFs) to provide the tailored confined reaction space for CO2 reduction. These design strategies have the potential to provide a framework for catalyst design with improved catalytic activity. To further gain mechanistic understanding in improving electrocatalysts’ selectivity toward CO2 reduction, in the fourth study, we utilize in situ and ex situ X-ray absorption spectroscopy (XAS) to investigate the electrocatalyst transformation in MOFs. We also develop a novel in situ XAS methodology to determine the active form of the electrocatalyst under operating conditions and to investigate the chemical state and the surrounding environment of the catalytic site during the electrochemical CO2 reduction. The combination of XAS measurements and product detection provides the mechanistic understanding that can stimulate the rational design for new classes of materials as CO2 reduction electrocatalysts. After gaining selectivity control for important C1 products, such as CO and formic acid, we would like to understand how to obtain more energy-dense hydrocarbon, like ethylene. In the fifth study, we investigate the role of surface and subsurface oxygen on the production of organic products from CO2 reduction over copper electrocatalysts through experiments and theoretical DFT calculation. Experimentally, we performed electrochemical CO2 reduction on copper with various concentrations of buried oxygen as a function of time, showing that the ethylene production is time-dependent and prolonged-time leads only to H2 evolution with negligible ethylene production. We utilize grand canonical potential-kinetics (GCP-K) DFT calculations to understand the experimental results. The combination of experimental results and theoretical calculation confirms the significance of surface and subsurface oxygen for the ethylene production in electrochemical CO2 reduction on the copper surface. Overall, these studies demonstrate that the activity and selectivity of the catalysts in chemical processes are not only dependent on the metal centers, but they are also heavily influenced by the local environment surrounding the metal centers. Therefore, to further improve the catalytic performance, it is crucial to also tune the catalytic microenvironments.