The preparation and rearrangement of a-carbomethoxy-a-lchloromethylltetrahydro-d-carbolines (9a,b) provided methyl l,2,3,6-tetrahydroazepino[4,5-6]indole-5-carboxylates (10a,b) and derivatives, which serve as intermediates in a series of alkaloid syntheses.

Reactions of methyl l,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate (5a) with aldehydes gave 3,10b-alkano bridged azepines 9-14,28, and 33. On interor intramolecular quaternization and treatment with base the salts 17-20, 29, and 34 derived from aldehydes with an -proton rearranged to the A, B, C, E (and D) ring system of vincadifformine-type alkaloids through initial generation of enamino acrylate analogues 25 of secodines. A corresponding condensation and intramolecular acylation reaction gave 3-oxovincadifformine (35) in 85% yield.In earlier syntheses of vincadifformine (1), the -vincadifformines (2), and the pandolines (3) through secodine (4) intermediates,1-5 we had utilized reactions of the indoloazepine esters 5a,b with halo aldehydes 6a,b or the

No abstract

The alkaloids ibophyllidine (1) and 20-epiibophyllidine (2) were selectively synthesized by utilizing reaction pathways which pass respectively either through a biomimetic ring D-seco intermediate, 8, or through a norsecodine intermediate, 13.

Condensation of methyl l,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate (6) with 5-chloro-2-ethyl-4hydroxypentanal lactol ( 14) yielded the 14a-and 14/3-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 with a (hydroxymethyl)-D-norvincadifformine, 10, as the major product.Dehydration of 14d-hydroxyvincadifformine (8a) readily gave tabersonine (1), while 14a-hydroxyvincadifformine (8b) could only be dehydrated by carbamate 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 14/3-chlorovincadifformine (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.