STEREOCONTROLLED EPOXIDATIONS OF CYCLOHEPTENE DERIVATIVES IN THE PALLADIUM-CATALYZED ROUTE TO TROPANE ALKALOIDS - TOTAL SYNTHESES OF SCOPINE AND PSEUDOSCOPINE

Stereoselective total syntheses of the tropane alkaloids scopine (1) and pseudoscopine (3) have been developed via the chloroacetoxylation approach. Palladium-catalyzed 1,4-chloroacetoxylation of diene 6 afforded the key intermediate 7. Subsequent substitution of the allylic chloride by TsNH-with either retention (Pd(O) catalysis) or inversion (S(N)2) of configuration gave 10 and 16, respectively. The epoxy oxygen was introduced syn to the nitrogen function prior to cyclization by utilizing the syn-directive effect of the allylic sulfonamido group in the epoxidation. Cyclization of the epoxides 12 and 21, followed by replacement of the tosyl group by a methyl group and subsequent debenzylation, afforded the title compounds 1 and 3, respectively.