S-F-Bindingsvorming en Generatie van Multidimensionale SuFEx-Elektrofielen: Brede Toepassingen en Verkenning van Radiolabeling

The field of chemical synthesis has played a pivotal role in scientific progress, leading to transformative breakthroughs through the creation of innovative synthetic approaches. This thesis explores novel synthetic strategies for the oxidative halogenation of thiols and disulfides, facilitating their conversion into valuable compounds with applications across various fields of chemistry. Additionally, it presents an innovative approach for synthesizing new SuFEx hubs and transforming them into diverse compounds in a safer and more reliable manner. Furthermore, a new application in radiochemistry is demonstrated by radiolabeling these compounds and evaluating their stability in aqueous media. In Chapter 1, we provide a brief overview of the element fluorine, highlighting its unique properties and the reasons behind its widespread incorporation into various compounds, particularly in medicinal applications. An introduction to SF5-containing compounds is presented, covering their synthesis and diverse applications in chemistry. Additionally, we explore chlorotetrafluorinated compounds, their reactivity, and their potential use as precursors for synthesizing SF4-bridged compounds. The thesis also delves into SuFEx chemistry and SuFEx hubs, discussing their properties, synthesis, and broad applicability, along with possible transformations. Furthermore, we examine the role of ¹⁸F as a radiotracer, detailing its properties and incorporation into compounds used for PET imaging. In Chapter 2, a novel method for oxidizing thiols is presented, eliminating the need for gas cylinders and costly equipment like a glove box. By optimizing reaction conditions, we achieve the selective formation of three distinct compounds with high yields. Additionally, we demonstrate the potential applications of SF4-derivatives in various post-transformations, including the synthesis of SF5-derivatives and the use of radical addition to generate SF4-bridged indoles and α-SF4R ketones. In Chapter 3, we present an innovative approach for synthesizing AgOSF5 as a SOF4 gas-free precursor and demonstrate its application in the synthesis of sulfurimidoyl fluorides. Traditionally, these fluorides were obtained using SOF4 gas, which requires harsh conditions and gas handling. By utilizing a commercially available reagent under ambient conditions, we achieve the quantitative synthesis of AgOSF5, which subsequently reacts with amines to afford sulfurimidoyl fluorides in high yields. Additionally, we introduce a new SuFEx hub, AgOSF4CF3, which enables the direct synthesis of sulfonimidoyl fluorides through a single-step reaction with amines, bypassing the previously required two-step process. Further post-transformations of these compounds are explored, highlighting their versatility and potential applications in chemistry. In Chapter 4, we report for the first time the radiolabeling of sulfurimidoyl and sulfonimidoyl fluorides through a rapid ¹⁹F-¹⁸F isotopic exchange. We investigate various substrates and their potential for radiolabeling, achieving consistently high and reproducible radiochemical conversions. Additionally, we assess their stability in aqueous media and plasma, demonstrating the strong potential of these compounds for the development of novel radiotracers.