Development of Palladium-Photoredox Catalyzed Trifluoromethylation Reactions Assisted by Statistical Tools

Abstract

Ensuring molecular diversity and structural complexity in a chemical space implies the continuous advancement of synthetic methodologies. The incorporation of fluorine into organic molecules, particularly in the pharmaceutical industry, is a highlighted theme. While these molecules hold industrial relevance, their presence in natural products is scarce, underscoring the critical need for the synthesis of fluorinated organic compounds. Efficient synthetic strategies with good atomic economy are essential in this context. Over the decades, various approaches to the synthesis of organofluorinated compounds have been developed, representing a promising area, especially considering that early methods often involved hazardous reagents and drastic conditions. Consequently, modern strategies, notably those employing transition metals, stand out for their versatility and selectivity, especially in trifluoromethylation reactions. Therefore, this project aims to explore this class of reactions, catalyzed by Pd-photoredox. Photocatalytic activation is particularly emphasized in this work, as the use of visible light allows for milder reaction conditions. Specifically, the research focuses on the development of direct trifluoromethylation reactions of olefins and alkynes via Heck-type reactions, as well as arenes and heteroarenes. Ligand selection is guided by chemoinformatic tools, including the construction of multivariate linear regression (MLR) models. Mechanistic investigations are also conducted using chemoinformatics strategies and NMR techniques, focusing on photochemical reactions.