222162-01-8Relevant articles and documents
Enantioselective Total Synthesis of Wieland-Gumlich Aldehyde and (-)-Strychnine
Sole, Daniel,Bonjoch, Josep,Garcia-Rubio, Silvina,Peidro, Emma,Bosch, Joan
, p. 655 - 665 (2007/10/03)
A total synthesis of (-)-strychnine in 15 steps from 1,3-cyclohexanedione in 0.15% overall yield is described. The sequence followed in the assembling of rings is: E → AE [2-(2-nitrophenyl)-1,3-cyclohexanedione] → ACE (3a-aryloctahydroindol-4-one) → ACDE (arylazatricyclic core) → ABCDE (strychnan skeleton) → ABCDEF (Wieland-Gumlich aldehyde) → ABCDEFG (strychnine). The key steps of the synthesis are the enantioselective construction of the 3a-(2-nitrophenyl)-octahydroindol-4-one ring system and the closure of the piperidine ring by a reductive Heck cyclization to generate the pivotal intermediate (-)-14. In contrast, a Lewis acid promoted α-alkoxy-propargylic silane-enone cyclization did not lead to synthetically useful azatricyclic ACDE intermediates. The introduction of C-17 and the closure of the indoline ring by reductive amination of the α-(2-nitrophenyl) ketone moiety complete the strychnan skeleton from which, via the Wieland-Gumlich aldehyde, the synthesis of (-)-strychnine is achieved.