A convergent stereoselective synthesis of the putative structure of the marine alkaloid lepadiformine via an intramolecular nitrone/1,3-diene dipolar cycloaddition

Journal of Organic Chemistry

Volumn 64, Issue 3, 1999, Pages 686-687

  Werner, Kim M ^a   De Los Santos, Jesus M ^a   Weinreb, Steven M ^a   Shang, Maoyu ^b  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

^b UNIVERSITY OF NOTRE DAME   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKADIENE; ALKALOID; LEPADIFORMINE; NITROGEN DERIVATIVE; NITRONE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; STEREOCHEMISTRY;

EID: 0033524881     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo981897+     Document Type: Article

References (27)

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11. For an example of an intramolecular nitrone/conjugated diene cycloaddition, see: Holmes, A. B.; Hughes, A. B.; Smith, A. L.; Williams, S. F. J. Chem. Soc., Perkin Trans. 1 1992, 1089. Intermolecular [3 + 2]-cycloaddition reactions of nitrones with conjugated dienes leading to indolizidines and quinolizidines have been described: (a) Tufariello, J. J. Acc. Chem. Res. 1979, 12, 396. (b) Tufariello, J. J.; Dyszlewski, A. D. J. Chem. Soc., Chem. Commun. 1987, 1138, and references cited.
12. For an example of an intramolecular nitrone/conjugated diene cycloaddition, see: Holmes, A. B.; Hughes, A. B.; Smith, A. L.; Williams, S. F. J. Chem. Soc., Perkin Trans. 1 1992, 1089. Intermolecular [3 + 2]-cycloaddition reactions of nitrones with conjugated dienes leading to indolizidines and quinolizidines have been described: (a) Tufariello, J. J. Acc. Chem. Res. 1979, 12, 396. (b) Tufariello, J. J.; Dyszlewski, A. D. J. Chem. Soc., Chem. Commun. 1987, 1138, and references cited.
13. For an example of an intramolecular nitrone/conjugated diene cycloaddition, see: Holmes, A. B.; Hughes, A. B.; Smith, A. L.; Williams, S. F. J. Chem. Soc., Perkin Trans. 1 1992, 1089. Intermolecular [3 + 2]-cycloaddition reactions of nitrones with conjugated dienes leading to indolizidines and quinolizidines have been described: (a) Tufariello, J. J. Acc. Chem. Res. 1979, 12, 396. (b) Tufariello, J. J.; Dyszlewski, A. D. J. Chem. Soc., Chem. Commun. 1987, 1138, and references cited.
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16. 7 was found to be a mixture of E/Z isomers after an aqueous workup and upon further chromatographic purification equilibrated totally to the E isomer. For NMR determination of oxime geometry, see: Bunnell, C. A.; Fuchs, P. L. J. Org. Chem. 1977, 42, 2614.
17. 2/imidazole (95%). We are grateful to Ann Bullion for performing these experiments. Experimental details will be provided in a full paper. (Matrix presented).
18. 5a,b to directly produce a cyclic nitrone like 16. However, all attempts to effect such a transformation led only to a 1,2-oxazine resulting from oxime O-alkylation (cf. Tiecco, M.; Testaferri, L.; Tingoli, M.; Bagnoli, L.; Marini, F. J. Chem. Soc., Perkin Trans, 1 1998, 1989).
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21. Interestingly, the simpler olefinic nitrone iv cyclizes thermally to afford the bridged regioisomeric isoxazolidine v as the major product along with the desired spirocyclic adduct vi. (Matrix presented)
22. 18
23. Martin, E. L. Org. React. 1942, 1, 155. Olefins have previously been observed as minor byproducts in Clemmensen reductions.
24. Since our synthetic compound does not correspond to natural lepadiformine, we have not attempted to optimize the direct removal of the carbonyl group from intermediate 20.
25. Aryl protection of alcohols has not been widely used. cf. Marshall, J. A.; Partridge, J. J. J. Am. Chem. Soc. 1968, 90, 1090. In this case, a p-chlorophenyl ether protecting group was used for oxygen.
26. We are grateful to Professors Barry Snider and A. J. Blackman for copies of the proton and carbon NMR spectra of several of the cylindricines. We also thank Dr. J. F. Biard for the proton and carbon NMR spectra, as well as a sample of lepadiformine, and Professor William H. Pearson (University of Michigan) for helpful discussions and exchange of information.
27. Pearson, W. H.; Ren, Y. J. Org. Chem. 1999, 64, 688.