title: Enantioselective total synthesis of Wieland-Gumlich aldehyde and (-)-strychnine
abstract: 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 a-alkoxypropargylic 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 alpha-(2-nitrophenyl) ketone moiety complete the strychnan skeleton from which, via the Wieland-Gumlich aldehyde, the synthesis of (-)-strychnine is achieved.
authors.affiliation: Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Spain.
authors.initials: D
authors.lastname: Sole
authors.initials: J
authors.lastname: Bonjoch
authors.initials: S
authors.lastname: Garcia-Rubio
authors.initials: E
authors.lastname: Peidro
authors.initials: J
authors.lastname: Bosch