The formal total synthesis of (±)-strychnine via a cobalt-mediated [2 + 2 + 2]cycloaddition

Organic Letters

Volumn 2, Issue 16, 2000, Pages 2479-2481

  Eichberg, Michael J ^a   Dorta, Rosa L ^a   Lamottke, Kai ^a   Vollhardt, K Peter C ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COBALT; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; STRYCHNINE;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; STEREOISOMERISM; SYNTHESIS;

COBALT; INDICATORS AND REAGENTS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; STEREOISOMERISM; STRYCHNINE;

EID: 0034632432     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol006131m     Document Type: Article

References (32)

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23. Critical to the success of this reaction is the addition rate of the cobalt reagent, the initial concentration of 3 (0.05 M), the temperature (0 °C). and the rate of the acetylene addition, which must be moderated by a concomitant nitrogen or argon purge of the reaction mixture.
24. The primary byproducts of this reaction, isolated in 20-30%, yield are the cis- and trans-cinnamic amides of N-acetyltryptamine. Presumably, these arise from the cyclization of the terminal acetylene of enyne 3 with two acetylene molecules and subsequent stereoequilibriation.
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30. For a closely related example reported in the synthesis of the Strychnos alkaloid mossambine, see: Kuehne, M. E.; Wang, T.; Seraphin, D. J. Org. Chem. 1996, 61, 7873.
31. Interestingly, this step is quite similar to a reduction of a late-stage pyridone intermediate in Woodward's original synthesis of strychnine (ref 1b). He attributes the selectivity to the directing effect of a free hydroxyl present in the substrate, while we rationalize our result by the attack of the hydride from the less-hindered si face.
32. Prelog, V.; Battegay, J.; Taylor, W. I. Helv. Chim. Acta 1948, 31, 2244. This ring closure step was also used as the last step in the strychnine syntheses of Woodward (ref 1), Kuehne (ref 2c), and Rawal (ref 2d).