The deoxygenation of scopolamine 1 to give 2 was achieved in near quantitative yield by reacting 1 with a zinc-copper couple4 in refluxing ethanol (a). The only impurity occasionally detected after filtration was hyoscyamine. The formation of hyoscyamine occurs presumably via hydrogenation of the double bond by hydrogen which was adsorbed on the surface of the zinc in the proccess of cleaning the zinc dust with 3% HCl prior to the formation of the zinc-copper couple. The next two steps were straight forward and involved (b), base hydrolysis to form 3 (77%) and (c), protection of the hydroxy group as the tert-butyldimethylsilyl ether 4 (88%).

The N-oxides 5 and 6 were generated in a ratio of 2:3 by stirring 4 with hydrogen peroxide in ethanol for 2 d (d). When a large excess of hydrogen peroxide was used, some epoxidation of the double bond was also observed which complicated the separation of the N-oxides 5 and 6.

The Meisenheimer Rearrangement

The thermolysis of both the N-oxides 5 and 6 in refluxing butyronitrile for 3 and 2 h respectively, gave the expected oxaza bridged bicyclic compound 7. The yields of 7, 53% from 6 and 15% from 5 could not be increased by solvent or temperature variation. This is to our knowledge is the first example of a Meisenheimer rearrangement of a tropane N-oxide5.

The TBDMS protected cycloheptadienol 8 was also formed in this reaction. The formation of 8 was found to result from the thermal decomposition of 7.