Fluorous Mitsunobu reactions and total synthesis of sixteen stereoisomers of pine sawfly sex pheromone by fluorous mixture synthesis

The ability of fluorous silica gel to separate compounds based on their fluorine content has resulted in new approaches for combinatorial chemistry and solution phase organic synthesis. A mixture of a fluorous compound and an organic compound can be separated by filtration over fluorous silica gel, a process often referred to as fluorous solid phase extraction (FSPE). A mixture of fluorous compounds with different fluorine contents can be predictably separated over fluorous silica gel by a high performance liquid chromatography. Such predictable separations dictate the success of fluorous mixture synthesis.; The first chapter in this thesis describes the synthesis and application of fluorous Mitsunobu reagents. A fluorous version of the popular reagent diethyl azodicarboxylate was developed and successfully employed in Mitsunobu reactions along with previously known and new fluorous phosphines. The fully fluorous Mitsunobu reactions were easy to conduct and allowed product isolation by rapid FSPE. The fluorous reagent based byproducts were separable and recyclable. A family of lighter fluorous hydrazides was synthesized and studied for potential removal by FSPE. Automated FSPE was introduced as an effective tool for solution phase parallel synthesis. The applicability of automated FSPE was demonstrated by isolating pure products from Mitsunobu reactions promoted by lighter fluorous reagents.; The second chapter describes the application of fluorous mixture synthesis for making natural products and their stereoisomers. All the sixteen stereoisomers of the sex pheromone of pine sawfly were synthesized by split-parallel FMS. Four fluorous p-methoxybenzyl protecting groups were used as tags and configurational diversity was introduced by splitting the mixture and reacting each of the splits with enantiomeric building blocks. Spectral data (1H and 13C NMR) obtained for all the sixteen isomers matched well with the data reported by Hedenstrom and co-workers.