Insight into 2α-Chloro-2′(2′,6′)-(Di)Halogenopicropodophyllotoxins Reacting with Carboxylic Acids Mediated by BF(3)·Et(2)O

Stereospecific nucleophilic substitution at the C-4α position of 2α-chloro-2′(2′,6′)-(di)halogenopicropodophyllotoxin derivatives with carboxylic acids mediated by BF(3)·Et(2)O was described. Interestingly, this stereoselective products were completely controlled by the reaction time. That is, if the reaction time was prolonged to 24.5–31 h, the resulting compounds were all transformed into the unusual C-ring aromatization products. Additionally, it demonstrated that BF(3)·Et(2)O and reaction temperature were the important factors for C-ring aromatization, and AlCl(3) could be substituted for BF(3)·Et(2)O as a lewis acid for C-ring aromatization. Halogenation of E-ring of 2β-chloropodophyllotoxins with NCS or NBS also led to the same C-ring aromatization compounds. Especially compounds 5c, 6g and 7b exhibited insecticidal activity equal to that of toosendanin.