cis-2-Methyl-6-substituted piperidin-3-ol alkaloids of the
Cassia and
Prosopis species are readily preparedby a combination of an aza-Achmatowicz oxidative rearrangement and dihydropyridone reduction followedby a stereoselective allylsilane addition to a
N-sulfonyliminium ion. The stereochemical outcome of thereduction reaction can be attributed to steric hindrance between the pseudoaxially oriented 2,6-substituentsand the equatorially approaching hydride reagent which explains the exclusive formation of the
cis-alcohol by axial approach of the hydride. The unsaturation present in the (
E)-methyl-pent-3-enoate sidechain was removed by catalytic reduction, and the remaining ester group was converted to thecorresponding Weinreb's amide. This key intermediate was utilized for the synthesis of azimic acid,deoxocassine, cassine, and spicigerine. The facile preparation of (
S)-
N-tosylamidofuran
16 and itsconversion to the chiral Achmatowicz oxidation product
18 provide a formal chiral synthesis of thesealkaloids.
