Indirect trapping of the retroconjugate addition reaction intermediate involved in the epimerization of lobeline: Application to the synthesis of (-)-sedamine

Journal of Organic Chemistry

Volumn 69, Issue 24, 2004, Pages 8514-8517

  Zheng, Guangrong ^a   Dwoskin, Linda P ^a   Crooks, Peter A ^a  

^a University of Kentucky   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADDITION REACTIONS; ALKYLATION; CHLORINE COMPOUNDS;

ALKYL CHLOROFORMATES; EPIMERIZATION; INDIRECT TRAPPING; RETROCONJUGATE ADDITION REACTIONS;

ORGANIC COMPOUNDS;

ALKYL GROUP; CHLORINE DERIVATIVE; FORMIC ACID DERIVATIVE; LOBELINE; SEDAMINE; UNCLASSIFIED DRUG;

ADDITION REACTION; ARTICLE; CONJUGATION; EPIMERIZATION; QUANTUM YIELD; REACTION ANALYSIS; SYNTHESIS;

ALKALOIDS; LOBELINE; MOLECULAR STRUCTURE; PIPERIDINES; STEREOISOMERISM;

EID: 9344254954     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo048848j     Document Type: Article

References (27)

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8. 3.
9. The retroconjugate addition reaction of 1a free base occurred in various organic solutions; however, in the solid state, no epimerization of 1a was observed even after storing for several years at room temperature. For a recent example of a retroconjugate addition reaction in the solid state, see: Tan, K.; Alvarez, R.; Nour M.; Cavé, C.; Chiaroni, A.; Riche, C.; d'Angelo, J. Tetrahedron Lett. 2001, 42, 5021-5023.
10. For an example of the trapping of a retroconjugate addition reaction intermediate with HCl, see: Vázquez, E.; Galindo, A.; Gnecco, D.; Bernès, S.; Terán, J. L.; Enríquez, R. G. Tetrahedron: Asymmetry 2001, 12, 3209-3211.
11. Reference 4 reported that a 1a/1b mixture could be converted to the single epimer 1a by treating the mixture with HCl, which probably indicates that the HCl salt of the cis isomer of lobeline (1a· HCl) is a thermodynamically stable species.
12. These studies indicate that lobeline does not undergo a retroconjugate addition reaction under acidic conditions.
13. 2O/NaOAc, see: Doll, M. K.-H.; Guggisberg, A.; Hesse, M. Helv. Chim. Acta 1996, 79, 973-981.
14. 1H NMR clearly showed signals of the double bond in these products, indicating the formation of the ring-open products.
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18. In our hands, compound I was converted to ring opening
19. The use of methyl chloroformate or benzyl chloroformate also afforded similar results; however, using AcCl under the same conditions resulted in no reaction.
20. 3N also gave similar results; however, the use of stronger bases such as NaOH or t-BuOK gave low conversion rates, probably because these strong bases destroyed the chloroformates during the reaction.
21. 3CN, were investigated quantitatively, the others were estimated from TLC data.
22. 3. MeOH and DMF gave no reaction.
23. 3CN; however, excessive water will afford a low conversion rate.
24. The reaction time was shortened when the molar ratio of TrocCl was increased or the temperature of the reaction was increased; however, the latter caused a decrease in yield.
25. Numerous syntheses of sedamine, either in racemic form or in enantiotopic form, have been reported; see: Angoli, M.; Barilli, A.; Lesma, G.; Passarella, D.; Riva, S.; Silvani, A.; Danieli, B. J. Org. Chem. 2003, 68, 9525-9527 and references therein; also see refs 4 and 5.
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