Synthesis and transformation of difluorinated Diels-Alder cycloadducts
This thesis describes the synthesis of highly substituted geminally difluorinated cyclohexenols based on Diels-Alder reactions between a difluorinated dienophile and furans (furan, 2-methyl and 2,3-dimenthyl) in presence of stannic chloride. The dienophile was synthesised in two different ways: a literature procedure, starting from the commercially available trifluoroethanol and new route involving an organometallic reagent.;Sulphur electrophile chemistry applied to the endo and exo cycloadducts gained stereo- and regio- control completely. Full protection of the free hydroxyl group was required before two different ring-opening strategies could be implemented: a carbanionic and a reductive method were attempted to ring-open the 7-oxabicyclo[2.2.1]heptenyl system. The scope of these methodologies was investigated with furan, 2-methyl and 2,3-dimethyl furan cycloadducts. When a stoichiometric amount of the Lewis acid (stannic chloride) was used in the cycloaddition with furan, an interesting bicyclic carbonate was afforded. To understand the mechanism of the reaction and the role of the Lewis acid in binding the cycloadduct, crystals were grown and an interesting complex was obtained.;Useful vinyl bromide products (endo and carbonate) were generated by cycloaddition between the difluorinated alkenoate and 3-bromofuran in the presence of 1.0 equivalents of tin tetrachloride. Suzuki coupling reaction of endoadduct with phenylboronic acid was carried out under Leadbeater's aqueous microwave conditions. Finally, dihydroxylation of the ring opened products and deprotections of the protected hydroxyl groups delivered the required gem- difluorinated polyhydroxy cyclohexane allowing for the first time the synthesis of cyclitol analogues via Diels-Alder reaction.