Method development, synthesis and mechanistic investigations of heteroaromatic compounds

Abstract

The presented thesis describes three different projects related to method development,synthesis and mechanistic investigations of hetereoaromatic compounds. Chapter 1 describes the endeavors towards the synthesis of cycloparaphenylenes, which are fragments of armchair carbon nanotubes. The retrosynthetic approach is discussed, as well as our synthetic strategy which provides a highly flexible synthesis for various sizes of cycloparaphenylenes via Sonogashira cross-coupling reactions and [2+2+2]-cycloadditions. After some preliminary experiments two generations of syntheses are discussed in detail. The first generation synthesis was based on an unfunctionalized alkyne and offers a concise sevenstep procedure to the cycloparaphenylenes. The second generation synthesis utilized customized building blocks, a functionalized alkyne and a masked iodoaryl, and offers a 15-step synthesis of functionalized cycloparaphenylenes. Both synthetic pathways have been explored and led to good to excellent yields for all steps. During this endeavor several challenges especially during the macrocyclization attempts were encountered. Until now the macrocycles could not be isolated from complex multiple-compound mixtures. This challenge, as well as the final [2+2+2]-cycloaddition reaction, remain the focus of the future work and have to be overcome to finally complete the synthesis successfully. Chapter 2 gives a description of the research concerning the photocyclization of Schiff’ Bases. Based on an optimization of the method, detailed mechanistic investigations of each step of the photocyclization sequence were conducted. All results combined led to the proposal of a new mechanism: Starting with a Lewis acid induced E/Z isomerization, followed by a conrotatory photocyclization the dihydrophenanthridine is formed. This intermediate cannot be trapped by oxidants or hydrogen absorbers but transfers the two hydrogen atoms directly to another molecule of the Schiff’ Base to form phenanthrindine and N-benzylphenylamine. The photocyclization occurs probably in a pre-equilibrium. Deuteration experiments indicated that the hydrogen atoms are transferred in a non ratedetermining step. This hydrogen transfer might take place via an excimer in an intramolecular fashion. Moreover, the method was applied to the synthesis of Trisphaeridine, a biological active natural product. Chapter 3 describes the application of a bidentate Lewis acid catalyst to the inverse electrondemand Diels-Alder reaction of five-membered heterocycles. The limitations of the uncatalyzed reactions were grasped and the application of a bidentate Lewis acid catalyst to expand the scope of the reaction towards less reactive dienes and dienophiles was studied. The coordination of the Lewis acid to the diazene moiety was observed in several cases via NMR-spectroscopy. Quantum chemical calculations indicated the required lowering of the energy of the LUMO orbitals. Unfortunately, in the experiments the accelerating effect of the catalyst was rather small in comparison to uncatalyzed reactions. To overcome this drawback, different more reactive catalysts will be developed in our group in the future. The experimental data and characterization of the compounds listed in this thesis are summarized in Chapter 4.