Approaches to the synthesis of (+)- and (-)-epibatidine

Synthetic approaches to the powerful analgesic alkaloids (+)- and (-)-epibatidine are described. The starting material employed was natural (-)-quinic acid from which chiral enones and alpha -iodoenones were prepared. Stille coupling afforded suitable substrates for completion of the syntheses. A key step in this process was the diastereoselective reduction of a cyclohexanone with sodium borohydride and DMSO which sets up the stereochemistry necessary for the formation of the bicycloheptane system. The synthesis of a previously reported enone intermediate has also been improved.