Studies in Biomimetic Alkaloid Syntheses. 8. Total Syntheses of the C-14 Epimeric Hydroxyvincadifformines, Tabersonine, a (Hydroxymethyl)-D-norvincadifformine, and the C-20 Epimeric Pandolines

Article abstract of DOI:10.1021/jo00346a034

Condensation of methyl 1,2,3,4,5,6-hexahydroazepino<4,5-b>indole-5-carboxylate (6) with 5-chloro-2-ethyl-4-hydroxypentanal lactol (14) yielded the 14α- and 14β-hydroxyvincadifformines (8a,b) in an epimeric ratio which was solvent dependent.On condensation of the indoloazepine 6 with 4,5-epoxy-2-ethylpentanal (9) the same compounds were formed together wih a (hydroxymethyl)-D-norvincadifformine, 10, as the major product.Dehydration of 14β-hydroxyvincadifformine (8a) readily gave tabersonine (1), while 14α-hydroxyvincadifformine (8b) could only be dehydrated bycarbamate pyrolysis.The latter compound (8b) and the (hydroxymethyl)-D-norvincadifformine 10 could be converted to vincadifformine (18) through the chloromethyl derivative 16.Condensation of the indoloazepine 6 with the epimeric 4,5-dichloro-2-ethylpentanals (19) also gave the (chloromethyl)-D-norvincadifformine 16 and 14β-chlorvinacadifformine (20).Dehydrohalogenation of the latter compound provided a third sequence to tabersonine (1).A synthesis of the C-20 epimeric pandolines (2a,b) from 5-chloro-4-ethyl-4-hydroxypentanal lactol (22) similarly allowed control of the C-20 epimeric product ratio through its solvent dependence.