Synthetic studies towards gelsemine, I The importance of the antiperiplanar effect in the highly regioselective reduction of non-symmetrical cis-hexahydrophthalimides

Abstract

During studies aimed at the total synthesis of gelsemine an exceptional example of regioselectivity has been discovered. cis-Hexahydrophtnalimides, which are non-symmetrical through the presence of one alkyl group (see Figure 1), are reduced by sodium borohydride into the corresponding hydroxy lactams with very high regioselectivity. The corresponding cis-tetrahydrophthalimides exhibit much lower selectivity. These findings are explained on the basis of the conformational preference of the imide molecule and the antiperiplanar effect.