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.

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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.

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