Rearrangements to vinyl substituted hetero- and carbocycles : Total synthesis of siphonazole B and otherapplications in oxazole and saturated ringsynthesis

Abstract: The aim of this thesis is to explore and develop new reactions for rapid generation of molecular complexity. Byenabling access to important molecules in a less wasteful and more cost-efficient manner such developmentbenefits the whole modern society, where increasingly complex molecules are needed to solve problems withinfields ranging from medicine, to materials sciences and the perfume industry.Reactions in which multiple bond-forming and -breaking events occur in a single step can be used to assemblelarge parts of target molecules such as natural products or pharmaceuticals in a reduced number of steps – savingtime, energy, and raw materials needed to complete the desired synthesis. Within this realm we developed thefirst domino synthesis of 4-vinyl oxazoles by merging a cyclocondensation reaction with an unprecedented 1,2-oxazole rearrangement process. We studied the reaction mechanism by DFT-calculation and demonstrated itsuse within a concise synthesis of the cytostatic natural product siphonazole B.The last chapter of this thesis discuss the development of a new iridium-catalyzed skeletal rearrangementprocess. The reaction was enabled by the design of a iridacyclooctene with a large barrier for reductiveelimination, and gives access to densely functionalized five-membered carbo and heterocycles from alkenetetheredvinylcyclopropanes.