Decarboxylative Claisen Rearrangement Reactions: Method Development and Applications to Total Synthesis

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We wish to carry out research to develop a new way we have invented of joining together small carbon-containing molecular pieces to make larger ones by making new carbon/carbon bonds. The novel process we have discovered involves firstly connecting together the pieces by forming easy-to-make esters through the combination of unsaturated alcohols with carboxylic acids containing a sulfonyl group. On heating the esters in the presence of a weak base and a silylating agent a rearrangement/fragmentation process takes place with the evolution of carbon dioxide. The formation of new carbon/carbon bonds in our process takes place with high selectivity, and enables the joining together of sterically demanding, bulky carbon fragments.We aim to assess the compatibility of the transformation with a number of different chemical groupings within the substrates, and to see if the chemistry works with groups other than sulfonyl next to the carboxylic esters. We plan also to look at substrates which may additionally contain heteroatoms.Finally, we wish to synthesise several biologically active natural products using our new reaction. One of these molecular targets is a member of a family of anti-cancer compounds isolated from a marine organism. Another is a potent analgesic and anti-inflammatory compound, whilst a third is a natural product related to vitamin D which has potential as a novel treatment for tuberculosis.