Total synthesis of ent-lycoricidine via a thiyl radical addition-cyclization sequence

Journal of Organic Chemistry

Volumn 61, Issue 24, 1996, Pages 8366-8367

  Keck, Gary E ^a   Wager, Travis T ^a  

^a UNIVERSITY OF UTAH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID; LYCORICIDINE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0029908898     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo961619f     Document Type: Article

References (31)

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13. For additional earlier examples see ref 4 and references cited therein. (a) Marco-Contelles, J.; Destabel, C.; Chiara, J. L.; Bernabe, M. Tetrahedron Asymmetry 1995, 6, 1547. (b) Naito, T.; Ninomiya, I.; Tajiri, K.; Kiguchi, T.; Hiramatsu, H. Tetrahedron Lett. 1995, 36, 253. (c) Marco-Contelles, J.; Chiara, J. L.; Khiar, N.; Gallego, P.; Destabel, C.; Bernabe, M. J. Org. Chem. 1995, 60, 6010. (d) Parker, K. A.; Fokas, D. J. Org. Chem. 1994, 59, 3927. (e) Booth, S. E.; Jenkins, P. R.; Swain, C. J.; Sweeney, J. B. J. Chem. Soc., Perkin Trans. 1 1994, 3499. (f) Parker, K. A.; Fokas, D. J. Org. Chem. 1994, 59, 3933. (g) Grissom, J. W.; Klingberg, D. J. Org. Chem. 1993, 58, 6559. (h) Pattenden, G.; Schulz, D. J. Tetrahedron Lett. 1993, 34, 6787.
14. For additional earlier examples see ref 4 and references cited therein. (a) Marco-Contelles, J.; Destabel, C.; Chiara, J. L.; Bernabe, M. Tetrahedron Asymmetry 1995, 6, 1547. (b) Naito, T.; Ninomiya, I.; Tajiri, K.; Kiguchi, T.; Hiramatsu, H. Tetrahedron Lett. 1995, 36, 253. (c) Marco-Contelles, J.; Chiara, J. L.; Khiar, N.; Gallego, P.; Destabel, C.; Bernabe, M. J. Org. Chem. 1995, 60, 6010. (d) Parker, K. A.; Fokas, D. J. Org. Chem. 1994, 59, 3927. (e) Booth, S. E.; Jenkins, P. R.; Swain, C. J.; Sweeney, J. B. J. Chem. Soc., Perkin Trans. 1 1994, 3499. (f) Parker, K. A.; Fokas, D. J. Org. Chem. 1994, 59, 3933. (g) Grissom, J. W.; Klingberg, D. J. Org. Chem. 1993, 58, 6559. (h) Pattenden, G.; Schulz, D. J. Tetrahedron Lett. 1993, 34, 6787.
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16. For additional earlier examples see ref 4 and references cited therein. (a) Marco-Contelles, J.; Destabel, C.; Chiara, J. L.; Bernabe, M. Tetrahedron Asymmetry 1995, 6, 1547. (b) Naito, T.; Ninomiya, I.; Tajiri, K.; Kiguchi, T.; Hiramatsu, H. Tetrahedron Lett. 1995, 36, 253. (c) Marco-Contelles, J.; Chiara, J. L.; Khiar, N.; Gallego, P.; Destabel, C.; Bernabe, M. J. Org. Chem. 1995, 60, 6010. (d) Parker, K. A.; Fokas, D. J. Org. Chem. 1994, 59, 3927. (e) Booth, S. E.; Jenkins, P. R.; Swain, C. J.; Sweeney, J. B. J. Chem. Soc., Perkin Trans. 1 1994, 3499. (f) Parker, K. A.; Fokas, D. J. Org. Chem. 1994, 59, 3933. (g) Grissom, J. W.; Klingberg, D. J. Org. Chem. 1993, 58, 6559. (h) Pattenden, G.; Schulz, D. J. Tetrahedron Lett. 1993, 34, 6787.
17. For additional earlier examples see ref 4 and references cited therein. (a) Marco-Contelles, J.; Destabel, C.; Chiara, J. L.; Bernabe, M. Tetrahedron Asymmetry 1995, 6, 1547. (b) Naito, T.; Ninomiya, I.; Tajiri, K.; Kiguchi, T.; Hiramatsu, H. Tetrahedron Lett. 1995, 36, 253. (c) Marco-Contelles, J.; Chiara, J. L.; Khiar, N.; Gallego, P.; Destabel, C.; Bernabe, M. J. Org. Chem. 1995, 60, 6010. (d) Parker, K. A.; Fokas, D. J. Org. Chem. 1994, 59, 3927. (e) Booth, S. E.; Jenkins, P. R.; Swain, C. J.; Sweeney, J. B. J. Chem. Soc., Perkin Trans. 1 1994, 3499. (f) Parker, K. A.; Fokas, D. J. Org. Chem. 1994, 59, 3933. (g) Grissom, J. W.; Klingberg, D. J. Org. Chem. 1993, 58, 6559. (h) Pattenden, G.; Schulz, D. J. Tetrahedron Lett. 1993, 34, 6787.
18. For additional earlier examples see ref 4 and references cited therein. (a) Marco-Contelles, J.; Destabel, C.; Chiara, J. L.; Bernabe, M. Tetrahedron Asymmetry 1995, 6, 1547. (b) Naito, T.; Ninomiya, I.; Tajiri, K.; Kiguchi, T.; Hiramatsu, H. Tetrahedron Lett. 1995, 36, 253. (c) Marco-Contelles, J.; Chiara, J. L.; Khiar, N.; Gallego, P.; Destabel, C.; Bernabe, M. J. Org. Chem. 1995, 60, 6010. (d) Parker, K. A.; Fokas, D. J. Org. Chem. 1994, 59, 3927. (e) Booth, S. E.; Jenkins, P. R.; Swain, C. J.; Sweeney, J. B. J. Chem. Soc., Perkin Trans. 1 1994, 3499. (f) Parker, K. A.; Fokas, D. J. Org. Chem. 1994, 59, 3933. (g) Grissom, J. W.; Klingberg, D. J. Org. Chem. 1993, 58, 6559. (h) Pattenden, G.; Schulz, D. J. Tetrahedron Lett. 1993, 34, 6787.
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20. For purposes of characterization, the major oxime isomer of all synthetic intermediates en route to ent-4 was isolated and characterized; for preparative purposes the mixture of oxime isomers was carried through the sequence.
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26. Aryl-substituted vinyl radicals appear to be linear: (a) Dolbier, W. R., Jr.; Bartberger, M. D. J. Org. Chem. 1995, 60, 4984. (b) Bennett, J. E.; Howard, J. A. Chem. Phys. Lett. 1971, 9, 460.
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28. 5a who observed very high yielding 5-exo cyclization upon stannyl radical additions to closely related terminal alkynes; undoubtedly, steric effects slow the rate of 5-exo cyclization in the present system.
29. This reaction has been extensively optimized and was found qualitatively to proceed better (faster reaction, higher isolated yields) at lower temperature rather than at elevated temperatures, a result that clearly seems related to the reversibility of the initial thiyl radical addition. For example, conducting the same reaction thermally (65°C) gave a 76% yield after 48 h.
30. Keck, G. E.; McHardy, S. F.; Wager, T. T. Tetrahedron Lett. 1995, 36, 7419.
31. 2 and long reaction times. Curiously, however, isolation and resubjection of 18 to these conditions affords 19.