This thesis deals with the development of new fluorination reactions and their application to fluorine-18 labelling. Fluorine-18 labelled compounds are employed as tracers in Positron Emission Tomography (PET), which is a powerful non-invasive imaging method in medical diagnostics.

The first part of this thesis focuses on the development of a late-stage halogen exchange-based fluorination method for the synthesis of trifluoromethylated molecules. The first project in this area relies on the application of a copper(I)-based fluorinating reagent to furnish trifluoroacetates, trifluorotoluenes and trifluoroacetamides. The second project involves the translation of this methodology into the fluorine-18 labelling of tertiary and secondary trifluoroacetamides. The targeted substrates were labelled in high radiochemical yield and high molar activity using [¹⁸F]Bu₄NF as fluorine source in the presence of an organic activator.

In the second part, the development of electrophilic fluorination reactions using a hypervalent iodine-based reagent is discussed. The first project in this area addresses the development of an electrophilic fluorine-18 fluorination reagent: [¹⁸F]fluoro-benziodoxole. The utility of this reagent was demonstrated in the labelling of [¹⁸F]fluoro-benzoxazepines. In the second project, the same [¹⁸F]fluoro-benziodoxole reagent was used in the rhodium-mediated synthesis of α-[¹⁸F]fluoroethers. High molar activities were obtained in these electrophilic labelling processes. In the third project, the fluorine-19 analog fluoro-benziodoxole was used in the palladium-catalyzed iodofluorination of allyl benzenes, styrenes and cycloalkenes. Both iodine and fluorine atoms in the product arise from the same reagent.

The dissertation work that is summarized in this thesis describes novel syntheses of organofluorine compounds with a broad coverage of different fluorine-containing motifs.

Chapter 2.1 covers works on the exploration of new trifluoromethylthiolating reactions of diazocarbonyl compounds. A rhodium-catalyzed oxy-trifluoromethylthiolation reaction enabled the synthesis of densely functionalized carbonyl compounds. Different oxygen nucleophiles, for instance alcohols, ethers and acetals underwent this transformation.

A zinc triflimide mediated three-component reaction established an arylation-trifluoromethylthiolation of diazocarbonyl compounds. In situ generation of triarylboranes was rendered most effective for the arylation event. Both procedures made use of the high reactivity of a recently developed electrophilic trifluoromethylthiolating reagent.

The second chapter (2.2) is dedicated to the late-stage construction of trifluoromethyl motifs. By means of halide exchange, nucleophilic fluoride from a copper(I)-complex could be used to exchange bromide with fluoride in the α-position to carbonyl groups as well as in benzylic positions.

The third chapter (2.3) covers the development of an enantioselective fluorocyclization reaction. In situ generated aryliodine(III)-fluoride species were used as organocatalysts. Through this oxidative olefin difunctionalization reaction, quaternary C-F stereogenic centers could be constructed with high enantiomeric excesses. DFT calculations enabled deeper understanding of the mechanism and the origin of stereoselectivity.