| Abstract
| - The Cp2TiCl-mediated rearrangement of 1,10-epoxy-11β,13-dihydrocostunolide (4) was carried outusing different solvents and additives to develop an expeditious procedure for the synthesis ofnatural eudesmanolides via free-radical chemistry. In the nonhalogenated solvents THF, benzene,and toluene the transannular cyclization, initiated by the homolytic opening of the oxirane ring,selectively led to the desired exocyclic alkene 5. When water was added to THF, however, the mainproduct was reduced eudesmanolide 8. Experiments with D2O confirmed that the H-4 of 8 comesfrom water. To rationalize these results, a mechanistic hypothesis based on a water-solvated Cp2TiCl complex is proposed. Finally, the usefulness of Cp2TiCl for the synthesis of naturaleudesmanolides has been proved using this reagent in the key step for the chemical preparation of(+)-3α-hydroxyreynosin (1) and (+)-reynosin (17). These syntheses confirmed the chemical structureof 1 and established the absolute stereochemistry of the natural products 1 and 17. The resultsobtained suggest that the combination of the biomimetic strategy employed, with Ti(III)-mediatedfree-radical chemistry, may come to represent a general method for the enantiospecific synthesisof more than 170 natural eudesmanolides containing an exocyclic double bond between C-4 andC-15.
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