ABC → ABCE/D Based Approaches to the Pentacyclic Ring System of the Vinca Alkaloids Using Intramolecular Hetero-[2+2]cycloaddition and Gold(I)-Catalyzed 6-endo-dig Cyclisation Protocols

Abstract

The angularly substituted tetrahydrocarbazole 13, which is readily obtained from cyclohexane-1,4-dione monoethylene ketal (6) using Fischer indole chemistry, has been converted into the isothiocyanate 16. Photolysis of this last compound affords, via an intramolecular hetero-[2+2]cycloaddition reaction, the pentacyclic "-thiolactam 17 that incorporates the ABCE ring substructure of natural products 1-3. Attempts to effect a two-carbon homologation of the four-membered ring within compound 17, and thereby establish the D-ring, failed. The azide 20, also obtained from compound 13, forms the cyclic imine 21 on thermolysis in refluxing toluene and the readily derived enamide 23 engages in a Au(I)-catalysed 6-endo-dig cyclisation reaction to give compound 24 embodying the ABCDE ring system of the title alkaloids. Show more