Supervisors: prof. Peeter Burk, TÜ Keemia Instituut
PhD Jaana Tammiku-Taul, TÜ Keemia Instituut
Opponents: Zoltán Novák, Assistant Professor, Eötvös Loránd University, Institute of Chemistry, Department of Organic Chemistry, Budapest, Hungary.
A large number of chemical reactions proceeds in the presence of catalyst. To improve the selectivity and rate of the reaction, design of more effective catalysts is very important. Transition metals have been found an extensive use in the field of organic synthesis as catalysts because among the other reactions they are capable of catalyzing the formation of carbon-carbon bonds. Since the discovery of cross-coupling reactions in the first half of the 1970s, metals in the subgroup of palladium have been/are widely used as catalysts. The possibility of selective formation of C-C bonds has strongly influenced organic chemistry, allowing the synthesis of desired molecules by combining suitable precursor fragments.
The Sonogashira cross-coupling, which was first described in 1975, is a palladium-catalyzed carbon-carbon bond formation reaction that is used to synthesize bisubstituted alkynes from organic halides and monosubstituted alkynes. This reaction allows the effective and fairly easy way to combine relatively small molecules to form alkynes with conjugated π-electron system, which are common fragments in bioactive substances and also important for pharmaceutical industry, agrochemistry, and material sciences.
Despite the wide use of the Sonogashira cross-coupling, the reaction mechanism has not been thoroughly studied and most of the information on this topic in literature is based on the data of organic synthesis. The deeper understanding of the rection mechanism is necessary for the development of more effective catalysts. Modern methods of computational chemistry offer a wide range of possibilities for the investigation of reaction mechanism, therefore, in the present thesis the Sonogashira cross-coupling is modeled by means of the density functional theory.
The obtained reaction mechanism is more complex than the previously reported analogues and is composed of four steps: oxidative addition, cis-trans isomerization, deprotonation (transmetalation), and reductive elimination. These steps incorporate multiple competing pathways, which depend on a number of additives in the reaction mixture, as well as the reactants and catalyst. The mechanism, described in this thesis, is a good starting point for both experimental and computational studies of similar cross-coupling reactions, as well as to find optimal reaction conditions for the Sonogashira cross-coupling.