Synthesis of Organofluorine Compounds and Allenylboronic Acids - Applications Including Fluorine-18 Labelling

Abstract: This work is focused on two areas: the chemistry of organofluorine and organoboron compounds. In the first chapter, a copper-catalysed synthesis of tri- and tetrasubstituted allenylboronic acids is presented. Extension of the same method leads to allenylboronic esters. The very reactive and moisture-sensitive allenylboronic acids are further applied to the reaction with aldehydes, ketones and imines to form homopropargyl alcohols and amines. In addition, an enantioselective reaction catalysed by a BINOL organocatalyst was developed to form tertiary alcohols with adjacent quaternary carbon stereocenters.The second chapter specialises in the functionalisation of 2,2-difluoro enol silyl ethers with electrophilic reagents under mild reaction conditions. This allowed for the formation of perfluoroethyl ketones, 2-aryl-2,2-difluoro ketones as well as the novel -COCF2SCF3-moiety. The third chapter continues with electrophilic fluorination. A synthesis of an electrophilic, 18F-labelled hypervalent iodine reagent from nucleophilic 18F-labelled tetrabutylammonium fluoride was devised. Then, the 18F-labelling of o-styryl benzamides using the developed reagent afforded [18F]benzoxazepines in good radiochemical yields and molar activity.The objective of the final chapter was the development of a method for the nucleophilic 18F-labelling of 2-halo-2,2-difluoro ketones derived from the corresponding 2,2-difluoro enol silyl ethers. The radiochemical utility of this method was demonstrated by fluorine-18 labelling of a potential neutrophil elastase ligand followed by successful preclinical studies.