Applications of vinylogous Mannich reactions. Total syntheses of the Ergotalkaloids rugulovasines A and B and setoclavine

Concise syntheses of the Ergot alkaloids rugulovasine A (3a), rugulovasine B (3b), and setoclavine (2) have been completed by strategies that feature inter- and intramolecular vinylogous Mannich reactions as the key steps. Th us, the first synthesis of 3a,b commenced with the conversion of the known indole 17 into 24 via the addition of the furan 22 to the iminium ion 21, w hich was generated in situ from the aldehyde 19. Cyclization of 24 by a nov el S(RN)1 reaction followed by removal of the N-benzyl group furnished a mi xture (1:2) of 3a and 3b. In an alternative approach to these alkaloids, th e biaryl 35 was reduced with DIBAL-H to give an intermediate imine that und erwent spontaneous cyclization via an intramolecular vinylogous Mannich add ition to provide 36a,b. N-Methylation of the derived benzyl carbamates 37a, b followed by global deprotection gave a mixture (2:1) of rugulovasines A a nd B (3a,b). Setoclavine (2) was then prepared from the biaryl 41 using a c losely related intramolecular vinylogous Mannich reaction to furnish the sp irocyclic lactones 42a,b. These lactones were subsequently transformed by h ydride reduction and reductive methylation into the ergoline derivatives 43 a,b, which were in turn converted into 2 by deprotection and solvolytic 1,3 -rearrangement of the allylic hydroxyl group.