SYNTHETIC STUDIES TOWARDS GELSEMINE .1. THE IMPORTANCE OF THE ANTIPERIPLANAR EFFECT IN THE HIGHLY REGIOSELECTIVE REDUCTION OF NONSYMMETRICAL CIS-HEXAHYDROPHTHALIMIDES

During studies aimed to the total synthesis of gelsemine an exceptional example of regioselectivity has been discovered. cis-Hexahydrophthalimides, 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-tetrahydrophthalamides exhibit much lower selectivity. These findings are explained on the basis of the conformational preference of the imide molecule and the antiperiplanar effect.