| Research Abstract |
This research has established a novel, short-step, convergent, and practical method for the synthesis of isocarbacyclin featuring a one-pot, three-step process involving vinyl ether formation, Claisen rearrangement, and en reaction to give bicyclo [3.3.1]-backbone, which is not relying on any previous idea in this field that is principally the same as that for prostaglandin synthesis. The new method provided in this research can construct cyclopentenone framework bearing the homoallylic omega-chain longer by one-carbon at first followed by the introduction of the alpha-chain shorter by two-carbon to furnish the precursor for the bicyclo [3.3.1]-backbone. The method required (4S)-4-(O-tert-butyldimethylsilyl)-cyclopent-2-en-1-one as an important starting chiral compound, the antipode of which has been well-known starting material in PG synthesis. In other words, therefore, (4S)-isomer is given significant value which has not been experienced so far.
A chiral synthon corresponding to the homoallylic omega-chain has been synthesized efficiently from (S)-1,2-(O-isopropylidene) glycerol in twenty-gram scale and 80-95% yield for each step through a series of routine reactions (7 steps).
A precursor for the bicyclo [3.3.1]-backbone to be submitted to the one-pot, three-step process can be provided from an allylic tert-alcohol by vinyl ether formation. We hoped that a reaction to be used in this transformation should be free from mercury salts for some reasons and, after several attempts, has succeeded in developing a new, general method for the synthesis of vinyl ether from various allylic alcohols including tert-versions.
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