Project Summary/Abstract The synthesis of stereochemically defined small molecules is tremendously important to solving biological problems, especially in identifying medicines for disease treatment. In many cases, the stereochemical information contained in a natural product or pharmaceutical compound is critical in determining its biological activity. Due to this general importance, innovative methods to rapidly determine molecular stereochemistry and stereoenrichment would be impactful. To this end, several research groups have recently reported stereochemical sensing assemblies that may assay enantiomeric excess (ee) using only spectroscopic methods (circular dichroism (CD), UV-Vis, and fluorescence). Most of these reports, however, are limited to the analysis of stereocenters α to the functional group that binds to the sensing motif and more remote stereocenters ( β, γ, δ, etc.) remain challenging to identify. To address this need, this proposal seeks to utilize data-driven methodologies to rationally design sensing assemblies capable of quantifying the ee of γ-stereogenic alcohols using only CD spectroscopy. These methodologies have been previously shown to effectively optimize chemical reactivity, but their use in chemical sensing has not yet been realized. While the proposed studies focus specifically on γ-stereogenic alcohols, it is anticipated that the workflows and design principles developed herein will be easily translated for further applications of optical stereochemical sensing.