New ferrocenyl chiral auxiliary substituents for amines: applications to syntheses of mossambine and vinblastine.

(+)−(R)-1,2-(α-(R)-Mesyloxy-β-dimethyltetramethylene)-ferrocene was synthesized and used as a chiral auxiliary for N-alkylation of methyl 1,2,3,4,5,6-hexahydroazepino[4,5-b] indole-5-ξ−carboxylates. Condensation with aldehydes then provided tetracyclic products in a diastereomeric ratio of at least 97:3. Gentle cleavage in acetic acid removed the chiral auxiliary to give the corresponding secondary amines in >99% ee. Thus, key intermediates leading to mossambine and vinblastine could be synthesized with high enantioselectivity. The enantioselectivity greatly exceeds that found with other chiral N-auxiliaries developed in our studies.