Practical synthetic methods for three unstable, unsaturated bromomethyl ketones, and on the use of near-orthogonal experiments for synthetic exploration.

The thesis consists of two different parts: The organic part presents the development of a convenient procedure for the synthesis of three rare, unstable α,β-unsaturated brominated methyl ketones from common commercially available regents. This family of molecule has been very challenging to synthesize and a short history about these efforts as well as different general strategies to produce them is presented. The route presented in this thesis is a convergent and highly efficient synthesis in terms of yield and reaction time and can be scaled-up with classic laboratory equipment. Several key steps of this procedure offer significant improvements over the earlier procedures. The synthetic use of the target molecules has been explored on four different types of reactions. The optimization part presents a new strategy for orthogonal experiments for the design of explorative experiments when the objective is to identify the important experimental variables as well as a new Near-Orthogonal strategy for design when the objective is to identify the important variables from few experiments. A short summery of existing orthogonal experiment is also presented. In conclusion, the synthesized compounds are sensitive to work with but allow access to new exotic heterocyclic molecules never synthesized before and the optimization introduces a new solution for faster detection of important experimental

On the synthesis of a fimbrolide

The present work is on the total synthesis of a natural compound found in a mixture of secondary metabolite produced by an alga nearby the cost of Australia. The target molecule, the 4-bromo-3-butyl-5-(dibromomethylene)furan-2(5H)-one, has not previously been proposed. The synthetic route described in this thesis uses cheap and readily available starting materials and the target is reached after six synthetic steps. Several new results have been obtained: selective monolithiation of a dibromofuran; Suzuki coupling with butyl boronic acid; a regioselective photo-oxidation of furan. The final step of the synthesis, a dibromoolefination, has not yet been accomplished