Development of the first Suzuki-Miyaura cross-coupling for the formation of alkylfluorostilbenes and studies of the E/Z- isomerization of (2-bromo-2-fluorovinyl)benzene derivatives

Abstract

Development of new methodologies for the synthesis of fluoro-organic compounds have gained great interest during the past decades, especially for applications in the fields of medical chemistry and agrochemistry. Introduction of fluorine atoms can substantially enhance biological properties such as bioavailability, lipophilicity, half-time and absorption.

The aim of this master's thesis is to develop the first Suzuki-Miyaura cross-coupling reaction leading to alkylfluorostilbenes in collaboration with the MSAP-team. Different reaction parameters like temperature or the nature of the catalyst have been investigated and the scope of the reaction has been identified. Secondly, the (E/Z) photo-isomerization of (E/Z)-(2-bromo-2-fluorovinyl)-benzene derivatives was studied. Different photosensitizers under UV irradiation (365 nm) were tested in order to enrich the mixture with only one isomer. Subsequently, effect of the solvent, temperature and substituents of the phenyl ring on the isomerization ratio and rate were investigated.

The first Suzuki-Miyaura cross-coupling reaction with (E/Z)-(2-bromo-2-fluorovinyl)-benzene derivatives and alkylboronic acids as coupling partners was developed with yields above 80% and maintaining excellent stereoselectivity. Regarding the isomerization reaction, 2 photosensitizers (benzil and 9-fluorenone) show promising results and further studies are still ongoing in the laboratory to obtain a robust protocol.