New ferrocenyl chiral auxiliary substituents for amines: applications to syntheses of mossambine and vinblastine.
(+)-(R)-1,2-(alpha-(R)-Mesyloxy-beta-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-xi-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.
Department of Chemistry, University of Vermont, Burlington, VT 05405, USA. mkuehne@zoo.uvm.edu
M E
ME
Kuehne
W
W
Dai
Y L
YL
Li
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D005296:Ferrous Compounds / Q000737:chemistry*; D000075163:Metallocenes; D015394:Molecular Structure; D013057:Spectrum Analysis; D013237:Stereoisomerism; D014747:Vinblastine / Q000138:chemical synthesis* / Q000737:chemistry
D000588:Amines; D005296:Ferrous Compounds; D000075163:Metallocenes; D014747:Vinblastine; C004998:ferrocene