222162-01-8

Upstream product

• 155206-86-3 (Z)-1-Bromo-4-[(tert-butyldimethylsilyl)oxy]-2-iodo-2-butene 
• 192431-42-8 (3aR,7aS)-3a-(2-Nitro-phenyl)-4-oxo-octahydro-indole-1-carboxylic acid 1-chloro-ethyl ester 
• 222162-00-7 (3aR,7aS)-3a-(2-Nitro-phenyl)-4-oxo-2,3,3a,4,7,7a-hexahydro-indole-1-carboxylic acid 1-chloro-ethyl ester 
• 192431-33-7 (3aR,7aS)-N-[(S)-α-Methylbenzyl]-3a-(2-nitrophenyl)octahydroindol-4-one 
• 504-02-9 1,3-cylohexanedione 
• 609-73-4 o-nitroiodobenzene 
• 264125-53-3 (Z)-4-[(tert-Butyldimethylsilyl)oxy]-2-iodo-1-(tetrahydropyran-2-yloxy)-2-butene 
• 264125-54-4 (Z)-4-[(tert-Butyldimethylsilyl)oxy]-2-iodo-2-butenol 
• 138040-07-0 2-Allyl-2-(2-nitrophenyl)-1,3-cyclohexanedione 
• 138040-06-9 3-allyloxy-2-(o-nitrophenyl)-2-cyclohexenone 
• 138040-05-8 3-hydroxy-2-(2-nitrophenyl)cyclohex-2-enone 

Downstream Products

• 57-24-9 strychnidin-10-one 
• 466-85-3 (17R,19E)-17,18-epoxy-cur-19-en-17-ol 
• 222162-02-9 (1R,7R,8S)-2-{(E)-2-[(tert-Butyldimethylsilyl)oxy]ethylidene}-7-(2-nitrophenyl)-4-azatricyclo[5.2.2.0^4,8]undecan-11-one 

Relevant academic research and scientific papers

Enantioselective Total Synthesis of Wieland-Gumlich Aldehyde and (-)-Strychnine

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.

Total synthesis of (-)-strychnine via the Wieland - Gumlich aldehyde

Fifteen steps suffice for an enantioselective total synthesis of (-)- strychnine (1) from 1,3-cyclohexanedione. The key steps are the easy generation of the enantiopure intermediate 2, the closure of the piperidine ring by a reductive Heck reaction, and the elaboration of the indoline nucleus in an advanced synthetic stage. TBDMS = tert-butyldimethylsilyl.