Transition-Metal Catalyzed Synthesis of Small- and Medium-Sized Rings Applications toward oxazole synthesis, cycloheptadienes, and natural products
Abstract: This thesis deals with the development of novel methodologies for the synthesis of hetero- and carbocycles enabled by transition metal catalysis. The second chapter of the thesis describes a gold-catalyzed three-component reaction to form a variety of substituted oxazoles from readily available N-benzylimines, terminal alkynes, and acyl chlorides. Sacrificial benzyl groups are used to merge two otherwise incompatible reactions: acetylide addition to acyl-iminium and cyclization of propargylamides to oxazoles. The mechanism of the reaction is studied by chemical observations and DFT-calculations. Conclusions made from the mechanistic studies were used to develop a non-catalyzed version of the reaction where N-benzyl propargylamines are reacted with acyl chlorides to form oxazoles in up to quantitative yields. Furthermore, this work has also led to the development of novel decarboxylation and 1,2-rearrangements with oxazoles as migrating group and a convenient method to access highly sensitive formylsilanes. In the third chapter, cationic iridium is used to catalyze the intramolecular 5+2 cycloaddition between vinyl-cyclopropanes and alkynes to form cycloheptadienes. The different reactivity of iridium compared to previously used transition-metals also led to the discovery of an efficient ?-hydride elimination to form 1,4-diene and an iridium catalyzed cyclopropanation. The fourth chapter describes efforts towards a recently discovered propellane natural product that is a possible lead compound in the battle against diabetes. An eight step synthesis of a late intermediate, containing all of the heavy atoms and the stereocenters with correct relative stereochemistry, is presented. The synthesis is initiated by a novel ruthenium-mediated Pauson-Khand reaction between an electron deficient alkyne and an ethylene-equivalent to introduce ten of the twenty-one heavy atoms of the target molecule.
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