Double Cycloisomerization as a Novel and Expeditious Route to Tricyclic Heteroaromatic Compounds: Short and Highly Diastereoselective Synthesis of (±)-Tetraponerine T6

Organic Letters

Volumn 4, Issue 26, 2002, Pages 4697-4699

  Kim, Joseph T ^a   Gevorgyan, Vladimir ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FUSED HETEROCYCLIC RINGS; INDOLIZIDINE 195B; INDOLIZIDINE-195B; INDOLIZINE DERIVATIVE; PYRIMIDINE DERIVATIVE; TETRAPONERINE T6;

ARTICLE; CHEMISTRY; ELECTRON; STEREOISOMERISM; SYNTHESIS;

ELECTRONS; HETEROCYCLIC COMPOUNDS, 3-RING; INDOLIZINES; PYRIMIDINES; STEREOISOMERISM;

EID: 0347812063     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol027129t     Document Type: Article

References (22)

1. Kel'in, A. V.; Sromek, A. W.; Gevorgyan, V. J. Am. Chem. Soc. 2001, 123, 2074.
2. Double pyrrolization of the unsubstituted bis-propynylpyrimidine proceeded with a somewhat lower yield, probably due to a competing polymerization process.
3. Possible allenic structures for the observed isomers were discounted, since propargyl-allenyl isomerization is a rate-determining step in the entire cycloisomerization; thus, allenyl intermediates were never detected during the reaction course. See refs 1 and 4.
4. Kel'in, A.; Gevorgyan, V. J. Org. Chem. 2002, 67, 95.
5. For lower thermal stability of the terminal allenic intermediates, see refs 1 and 4.
6. -9 mol/ant mg) have made them attractive synthetic targets for chemists: see refs 2b and 4. To date, four diastereo- and enatioselective syntheses of tetraponerine T6 have been described: see: (a) Stragies, R.; Blecher, S. J. Am. Chem. Soc. 2000, 122, 9584. (b) Yue, C.; Gauthier, I.; Royer, J.; Husson, H. P. J. Org. Chem. 1996, 61, 4949. (c) Plehiers, M.; Heilporn, S.; Ekelmans, D.; Leclercq, S.; Sangermano, M.; Braekman, J. C.; Daloze, D. Can. J. Chem. 2000, 78, 1030. (d) Devijver, C.; Macours, P.; Braekman, J. C.; Daloze, D.; Pasteels, J. M. Tetrahedron, 1995, 40, 10913.
7. -9 mol/ant mg) have made them attractive synthetic targets for chemists: see refs 2b and 4. To date, four diastereo- and enatioselective syntheses of tetraponerine T6 have been described: see: (a) Stragies, R.; Blecher, S. J. Am. Chem. Soc. 2000, 122, 9584. (b) Yue, C.; Gauthier, I.; Royer, J.; Husson, H. P. J. Org. Chem. 1996, 61, 4949. (c) Plehiers, M.; Heilporn, S.; Ekelmans, D.; Leclercq, S.; Sangermano, M.; Braekman, J. C.; Daloze, D. Can. J. Chem. 2000, 78, 1030. (d) Devijver, C.; Macours, P.; Braekman, J. C.; Daloze, D.; Pasteels, J. M. Tetrahedron, 1995, 40, 10913.
8. -9 mol/ant mg) have made them attractive synthetic targets for chemists: see refs 2b and 4. To date, four diastereo- and enatioselective syntheses of tetraponerine T6 have been described: see: (a) Stragies, R.; Blecher, S. J. Am. Chem. Soc. 2000, 122, 9584. (b) Yue, C.; Gauthier, I.; Royer, J.; Husson, H. P. J. Org. Chem. 1996, 61, 4949. (c) Plehiers, M.; Heilporn, S.; Ekelmans, D.; Leclercq, S.; Sangermano, M.; Braekman, J. C.; Daloze, D. Can. J. Chem. 2000, 78, 1030. (d) Devijver, C.; Macours, P.; Braekman, J. C.; Daloze, D.; Pasteels, J. M. Tetrahedron, 1995, 40, 10913.
9. -9 mol/ant mg) have made them attractive synthetic targets for chemists: see refs 2b and 4. To date, four diastereo- and enatioselective syntheses of tetraponerine T6 have been described: see: (a) Stragies, R.; Blecher, S. J. Am. Chem. Soc. 2000, 122, 9584. (b) Yue, C.; Gauthier, I.; Royer, J.; Husson, H. P. J. Org. Chem. 1996, 61, 4949. (c) Plehiers, M.; Heilporn, S.; Ekelmans, D.; Leclercq, S.; Sangermano, M.; Braekman, J. C.; Daloze, D. Can. J. Chem. 2000, 78, 1030. (d) Devijver, C.; Macours, P.; Braekman, J. C.; Daloze, D.; Pasteels, J. M. Tetrahedron, 1995, 40, 10913.
10. -9 mol/ant mg) have made them attractive synthetic targets for chemists: see refs 2b and 4. To date, four diastereo- and enatioselective syntheses of tetraponerine T6 have been described: see: (a) Stragies, R.; Blecher, S. J. Am. Chem. Soc. 2000, 122, 9584. (b) Yue, C.; Gauthier, I.; Royer, J.; Husson, H. P. J. Org. Chem. 1996, 61, 4949. (c) Plehiers, M.; Heilporn, S.; Ekelmans, D.; Leclercq, S.; Sangermano, M.; Braekman, J. C.; Daloze, D. Can. J. Chem. 2000, 78, 1030. (d) Devijver, C.; Macours, P.; Braekman, J. C.; Daloze, D.; Pasteels, J. M. Tetrahedron, 1995, 40, 10913.
11. -9 mol/ant mg) have made them attractive synthetic targets for chemists: see refs 2b and 4. To date, four diastereo- and enatioselective syntheses of tetraponerine T6 have been described: see: (a) Stragies, R.; Blecher, S. J. Am. Chem. Soc. 2000, 122, 9584. (b) Yue, C.; Gauthier, I.; Royer, J.; Husson, H. P. J. Org. Chem. 1996, 61, 4949. (c) Plehiers, M.; Heilporn, S.; Ekelmans, D.; Leclercq, S.; Sangermano, M.; Braekman, J. C.; Daloze, D. Can. J. Chem. 2000, 78, 1030. (d) Devijver, C.; Macours, P.; Braekman, J. C.; Daloze, D.; Pasteels, J. M. Tetrahedron, 1995, 40, 10913.
12. See Supporting Information for details.
13. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467.
14. (b) Sonogashira, K. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: New York, 1991, Vol. 3, p 521.
15. For hydrogenation of pyrimidines, see: (a) Brown, D. J. The Pyrimidines. In The Chemistry of Heterocyclic Compounds; Wiley & Sons: New York, 1994; Vol. 52, pp 790-793. (b) Brown, D. J. T. The Pyrimidines Supplement I. In The Chemistry of Heterocyclic Compounds; Wiley & Sons: New York, 1970; pp 337-341.
16. For hydrogenation of pyrimidines, see: (a) Brown, D. J. The Pyrimidines. In The Chemistry of Heterocyclic Compounds; Wiley & Sons: New York, 1994; Vol. 52, pp 790-793. (b) Brown, D. J. T. The Pyrimidines Supplement I. In The Chemistry of Heterocyclic Compounds; Wiley & Sons: New York, 1970; pp 337-341.
17. 13C NMR analysis of crude 9 revealed that it is a single diastereomer. The relative configuration of its stereogenic centers was proved by a NOE experiment after the subsequent reduction step.
18. For stereoelectronic control in addition of nucleophiles to an amidinium ion, see: (a) Perrin, C. L.; Young, D. B. J. Am. Chem. Soc. 2001, 123, 4451. (b) Fülöp, F.; Simon, K.; Tóth, G.; Hermecz, I.; Mészáros, Z.; Bernáth, G. J. Chem. Soc., Perkin Trans. 1982, 12, 2801. (c) Kirby, A. J. Stereoelectronic Effects, Oxford Chemistry Primer no. 36; Oxford University Press: Oxford, 1996; pp 54-55. (d) Barluenga, J.; Tomás, M.; Kouznetsov, V.; Rubio, E. J. Org. Chem. 1994, 59, 3699.
19. For stereoelectronic control in addition of nucleophiles to an amidinium ion, see: (a) Perrin, C. L.; Young, D. B. J. Am. Chem. Soc. 2001, 123, 4451. (b) Fülöp, F.; Simon, K.; Tóth, G.; Hermecz, I.; Mészáros, Z.; Bernáth, G. J. Chem. Soc., Perkin Trans. 1982, 12, 2801. (c) Kirby, A. J. Stereoelectronic Effects, Oxford Chemistry Primer no. 36; Oxford University Press: Oxford, 1996; pp 54-55. (d) Barluenga, J.; Tomás, M.; Kouznetsov, V.; Rubio, E. J. Org. Chem. 1994, 59, 3699.
20. For stereoelectronic control in addition of nucleophiles to an amidinium ion, see: (a) Perrin, C. L.; Young, D. B. J. Am. Chem. Soc. 2001, 123, 4451. (b) Fülöp, F.; Simon, K.; Tóth, G.; Hermecz, I.; Mészáros, Z.; Bernáth, G. J. Chem. Soc., Perkin Trans. 1982, 12, 2801. (c) Kirby, A. J. Stereoelectronic Effects, Oxford Chemistry Primer no. 36; Oxford University Press: Oxford, 1996; pp 54-55. (d) Barluenga, J.; Tomás, M.; Kouznetsov, V.; Rubio, E. J. Org. Chem. 1994, 59, 3699.
21. For stereoelectronic control in addition of nucleophiles to an amidinium ion, see: (a) Perrin, C. L.; Young, D. B. J. Am. Chem. Soc. 2001, 123, 4451. (b) Fülöp, F.; Simon, K.; Tóth, G.; Hermecz, I.; Mészáros, Z.; Bernáth, G. J. Chem. Soc., Perkin Trans. 1982, 12, 2801. (c) Kirby, A. J. Stereoelectronic Effects, Oxford Chemistry Primer no. 36; Oxford University Press: Oxford, 1996; pp 54-55. (d) Barluenga, J.; Tomás, M.; Kouznetsov, V.; Rubio, E. J. Org. Chem. 1994, 59, 3699.
22. 1H NOE experiments of 6, see Supporting Information.