Enantioselective total synthesis of Wieland-Gumlich aldehyde and (-)-strychnine

A total synthesis of (-)-strychnine in 15 steps from 1,3-cyclohexanedione i n 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-ary loctahydroindol-4-one) --> ACDE (arylazatricyclic core) ABCDE (strychnan sk eleton) --> 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 pip eridine ring by a reductive Heck cyclization to generate the pivotal interm ediate (-)-14. In contrast, a Lewis acid promoted alpha-alkoxy-propargylic silane-enone cyclization did not lead to synthetically useful azatricyclic ACDE intermediates. The introduction of C-17 and the closure of the indolin e ring by reductive amination of the alpha-(2-nitrophenyl) ketone moiety co mplete the strychnan skeleton from which, via the Wieland-Gumlich aldehyde, the synthesis of (-)-strychnine is achieved.