167695-96-7Relevant articles and documents
Asymmetric total synthesis of (R)-(-)-cryptopleurine and (R)-(-)-julandine via highly enantioselective amidoalkylations with N-acylhydrazonium salts
Suzuki,Aoyagi,Kibayashi
, p. 6114 - 6122 (2007/10/03)
The first enantioselective total syntheses of the phenanthroquinolizidine alkaloid (-)-cryptopleurine (1) and its seco base (-)-julandine [(R)-3] are described. The synthesis of (R)-3 allowed the 9aS configuration to be assigned to natural dextrorotatory julandine as shown by structure (S)-3. Both synthetic approaches are based on the high degree of 1,3-asymmetric induction achieved using an N-acylhydrazonium salt, which belongs to a new structural class of activated azomethines. Upon exposure of methoxylactam 9, with a chiral 2-substituted pyrrolidine auxiliary, to BF3·Et2O and a silyl enol ether the in situ generated N-acylhydrazonium intermediate 10 underwent asymmetric nucleophilic addition to give the (6R)-keto lactams 13 and 14 with complete diastereoselectivity. On the other hand, nucleophilic addition to the N-acylhydrazonium ion 25, with an acyclic chiral auxiliary, showed poor diastereoselectivity. From these results, the high degree of diastereoselection observed for the N-acylhydrazonium ion 10 can be rationalized in terms of the pyramidal stability of the trivalent nitrogen in the chiral pyrrolidine auxiliary. Removal of the chiral auxiliary from 13 and 14 was achieved by reductive N-N bond cleavage using BH3·THF, affording (2S)-piperidine derivatives 15 and 31, respectively, which were transformed into quinolizidinones 30 and 35, respectively, via intramolecular aldol condensation. Reduction of 30 with alane provided (-)julandine [(R)-3]. In addition, 35 was converted to (-)-cryptopleurine (1) in two steps, by radical cyclization with Bu3SnH and AIBN, followed by LiAlH4 reduction.
