Efficient synthesis of a tricyclic BCD analogue of ouabain: Lewis acid catalyzed Diels-Alder reactions of sterically hindered systems

Angewandte Chemie - International Edition

Volumn 41, Issue 21, 2002, Pages 4125-4128

  Jung, Michael E ^a   Davidov, Pablo ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cycloaddition; Diastereoselectivity; Diels Alder reaction; Lewis acids; Synthetic methods

Indexed keywords

ALCOHOLS; CATALYSIS; ETHERS; HYDROLYSIS; OXIDATION; REDUCTION;

DESILYLATION;

SYNTHESIS (CHEMICAL);

ACID; DRUG DERIVATIVE; LEWIS ACID; OUABAIN; OUABAIN DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CHEMICAL REACTION; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; CYCLOADDITION; DIELS ALDER REACTION; PH; REACTION ANALYSIS; STEREOCHEMISTRY; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ACIDS; CATALYSIS; CRYSTALLOGRAPHY, X-RAY; HYDROGEN-ION CONCENTRATION; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; OUABAIN;

EID: 0037021092     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/1521-3773(20021104)41:21<4125::AID-ANIE4125>3.0.CO;2-E     Document Type: Article

References (37)

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8. Overman and co-workers have reported significant progress toward the total synthesis of ouabain. a) L. E. Overman, P. V. Rucker, Heterocycles 2000, 52, 1297; b) S. Laschat, F. Narjes, L. E. Overman, Tetrahedron 1999, 55, 347; c) L. E. Overman, P. V. Rucker, Tetrahedron Lett. 1998, 39, 4643: d) J. Hynes, Jr., L. E. Overman, T. Nasser, P. V. Rucker, Tetrahedron Lett. 1998, 39, 4647; e) W. Deng, M. S. Jensen, L. E. Overman, P. V. Rucker, J. P. Vionnet, J. Org. Chem. 1996, 61, 6760.
9. Overman and co-workers have reported significant progress toward the total synthesis of ouabain. a) L. E. Overman, P. V. Rucker, Heterocycles 2000, 52, 1297; b) S. Laschat, F. Narjes, L. E. Overman, Tetrahedron 1999, 55, 347; c) L. E. Overman, P. V. Rucker, Tetrahedron Lett. 1998, 39, 4643: d) J. Hynes, Jr., L. E. Overman, T. Nasser, P. V. Rucker, Tetrahedron Lett. 1998, 39, 4647; e) W. Deng, M. S. Jensen, L. E. Overman, P. V. Rucker, J. P. Vionnet, J. Org. Chem. 1996, 61, 6760.
10. Overman and co-workers have reported significant progress toward the total synthesis of ouabain. a) L. E. Overman, P. V. Rucker, Heterocycles 2000, 52, 1297; b) S. Laschat, F. Narjes, L. E. Overman, Tetrahedron 1999, 55, 347; c) L. E. Overman, P. V. Rucker, Tetrahedron Lett. 1998, 39, 4643: d) J. Hynes, Jr., L. E. Overman, T. Nasser, P. V. Rucker, Tetrahedron Lett. 1998, 39, 4647; e) W. Deng, M. S. Jensen, L. E. Overman, P. V. Rucker, J. P. Vionnet, J. Org. Chem. 1996, 61, 6760.
11. Overman and co-workers have reported significant progress toward the total synthesis of ouabain. a) L. E. Overman, P. V. Rucker, Heterocycles 2000, 52, 1297; b) S. Laschat, F. Narjes, L. E. Overman, Tetrahedron 1999, 55, 347; c) L. E. Overman, P. V. Rucker, Tetrahedron Lett. 1998, 39, 4643: d) J. Hynes, Jr., L. E. Overman, T. Nasser, P. V. Rucker, Tetrahedron Lett. 1998, 39, 4647; e) W. Deng, M. S. Jensen, L. E. Overman, P. V. Rucker, J. P. Vionnet, J. Org. Chem. 1996, 61, 6760.
12. Overman and co-workers have reported significant progress toward the total synthesis of ouabain. a) L. E. Overman, P. V. Rucker, Heterocycles 2000, 52, 1297; b) S. Laschat, F. Narjes, L. E. Overman, Tetrahedron 1999, 55, 347; c) L. E. Overman, P. V. Rucker, Tetrahedron Lett. 1998, 39, 4643: d) J. Hynes, Jr., L. E. Overman, T. Nasser, P. V. Rucker, Tetrahedron Lett. 1998, 39, 4647; e) W. Deng, M. S. Jensen, L. E. Overman, P. V. Rucker, J. P. Vionnet, J. Org. Chem. 1996, 61, 6760.
13. M. E. Jung, P. Davidov, Org. Lett. 2001, 3, 3025; for earlier work in this area, see: M. E. Jung, P. Davidov, Org. Lett. 2001, 3. 627.
14. M. E. Jung, P. Davidov, Org. Lett. 2001, 3, 3025; for earlier work in this area, see: M. E. Jung, P. Davidov, Org. Lett. 2001, 3. 627.
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16. An attempt to effect a tandem Michael-Michael process by treating the silyl enol ether with methyllithium consumed the starting material but no desired bicyclic product was isolated.
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19. IH NMR spectrum of the crude product mixture and thus is most likely compound 9.
20. For examples of somewhat hindered cycloadditions of this type, see: a) T. Fujiwara, T. Ohsaka, T. Inoue, T. Takeda, Tetrahedron Lett. 1988, 29, 6283; b) I. S. Levina, L. E. Kulikova, A. V. Kamernitskii, B. S. El'yanov, E. M. Gonikberg, Izv. Akad. Nauk, Ser. Khim. 1992, 1622; c) R. D. Hubbard, B. L. Miller, J. Org. Chem. 1998, 63, 4143.
21. For examples of somewhat hindered cycloadditions of this type, see: a) T. Fujiwara, T. Ohsaka, T. Inoue, T. Takeda, Tetrahedron Lett. 1988, 29, 6283; b) I. S. Levina, L. E. Kulikova, A. V. Kamernitskii, B. S. El'yanov, E. M. Gonikberg, Izv. Akad. Nauk, Ser. Khim. 1992, 1622; c) R. D. Hubbard, B. L. Miller, J. Org. Chem. 1998, 63, 4143.
22. For examples of somewhat hindered cycloadditions of this type, see: a) T. Fujiwara, T. Ohsaka, T. Inoue, T. Takeda, Tetrahedron Lett. 1988, 29, 6283; b) I. S. Levina, L. E. Kulikova, A. V. Kamernitskii, B. S. El'yanov, E. M. Gonikberg, Izv. Akad. Nauk, Ser. Khim. 1992, 1622; c) R. D. Hubbard, B. L. Miller, J. Org. Chem. 1998, 63, 4143.
23. Although this Diels-Alder reaction, could be a concerted [4+2] cycloaddition, we propose that the cycloaddition occurs by a stepwise mechanism, namely a double Mukaiyama-type Michael addition rather than a concerted [4+2] cycloaddition and thus produces the exo product as the major isomer. For an example of a Diels-Alder reaction of the diene 6 with 2-methylcyclohexenone under Lewis acid catalysis to give mainly the endo adduct, see: a) M. Ge, B. M. Stoltz, E. J. Corey, Org. Lett. 2000, 2, 1927; since the endo isomer is the minor isomer in our case, we favor the double Michael process. For examples of Mukaiyama Michael additions, see: b) K. Narasaki, K. Soai. T. Mukaiyama, Chem. Lett. 1974, 1223; c) D. A. Evans, K. A. Scheidt, J. N. Johnston, M. C. Willis, J. Am. Chem. Soc. 2001, 123, 4480; d) G. Desimoni, G. Faita, S. Filippone, M. Mella, M. G. Zampori, M. Zema, Tetrahedron 2001, 57, 10203; for examples of double Michael additions to produce [4+2] cycloadducts, see: e) M. E. Jung in Comprehensive Organic Synthesis, Vol. 4 (Ed.: B. M. Trost), Pergamon, Oxford, 1991, chap. 1.1, pp. 1-67 (especially pp. 30-32).
24. Although this Diels-Alder reaction, could be a concerted [4+2] cycloaddition, we propose that the cycloaddition occurs by a stepwise mechanism, namely a double Mukaiyama-type Michael addition rather than a concerted [4+2] cycloaddition and thus produces the exo product as the major isomer. For an example of a Diels-Alder reaction of the diene 6 with 2-methylcyclohexenone under Lewis acid catalysis to give mainly the endo adduct, see: a) M. Ge, B. M. Stoltz, E. J. Corey, Org. Lett. 2000, 2, 1927; since the endo isomer is the minor isomer in our case, we favor the double Michael process. For examples of Mukaiyama Michael additions, see: b) K. Narasaki, K. Soai. T. Mukaiyama, Chem. Lett. 1974, 1223; c) D. A. Evans, K. A. Scheidt, J. N. Johnston, M. C. Willis, J. Am. Chem. Soc. 2001, 123, 4480; d) G. Desimoni, G. Faita, S. Filippone, M. Mella, M. G. Zampori, M. Zema, Tetrahedron 2001, 57, 10203; for examples of double Michael additions to produce [4+2] cycloadducts, see: e) M. E. Jung in Comprehensive Organic Synthesis, Vol. 4 (Ed.: B. M. Trost), Pergamon, Oxford, 1991, chap. 1.1, pp. 1-67 (especially pp. 30-32).
25. Although this Diels-Alder reaction, could be a concerted [4+2] cycloaddition, we propose that the cycloaddition occurs by a stepwise mechanism, namely a double Mukaiyama-type Michael addition rather than a concerted [4+2] cycloaddition and thus produces the exo product as the major isomer. For an example of a Diels-Alder reaction of the diene 6 with 2-methylcyclohexenone under Lewis acid catalysis to give mainly the endo adduct, see: a) M. Ge, B. M. Stoltz, E. J. Corey, Org. Lett. 2000, 2, 1927; since the endo isomer is the minor isomer in our case, we favor the double Michael process. For examples of Mukaiyama Michael additions, see: b) K. Narasaki, K. Soai. T. Mukaiyama, Chem. Lett. 1974, 1223; c) D. A. Evans, K. A. Scheidt, J. N. Johnston, M. C. Willis, J. Am. Chem. Soc. 2001, 123, 4480; d) G. Desimoni, G. Faita, S. Filippone, M. Mella, M. G. Zampori, M. Zema, Tetrahedron 2001, 57, 10203; for examples of double Michael additions to produce [4+2] cycloadducts, see: e) M. E. Jung in Comprehensive Organic Synthesis, Vol. 4 (Ed.: B. M. Trost), Pergamon, Oxford, 1991, chap. 1.1, pp. 1-67 (especially pp. 30-32).
26. Although this Diels-Alder reaction, could be a concerted [4+2] cycloaddition, we propose that the cycloaddition occurs by a stepwise mechanism, namely a double Mukaiyama-type Michael addition rather than a concerted [4+2] cycloaddition and thus produces the exo product as the major isomer. For an example of a Diels-Alder reaction of the diene 6 with 2-methylcyclohexenone under Lewis acid catalysis to give mainly the endo adduct, see: a) M. Ge, B. M. Stoltz, E. J. Corey, Org. Lett. 2000, 2, 1927; since the endo isomer is the minor isomer in our case, we favor the double Michael process. For examples of Mukaiyama Michael additions, see: b) K. Narasaki, K. Soai. T. Mukaiyama, Chem. Lett. 1974, 1223; c) D. A. Evans, K. A. Scheidt, J. N. Johnston, M. C. Willis, J. Am. Chem. Soc. 2001, 123, 4480; d) G. Desimoni, G. Faita, S. Filippone, M. Mella, M. G. Zampori, M. Zema, Tetrahedron 2001, 57, 10203; for examples of double Michael additions to produce [4+2] cycloadducts, see: e) M. E. Jung in Comprehensive Organic Synthesis, Vol. 4 (Ed.: B. M. Trost), Pergamon, Oxford, 1991, chap. 1.1, pp. 1-67 (especially pp. 30-32).
27. Although this Diels-Alder reaction, could be a concerted [4+2] cycloaddition, we propose that the cycloaddition occurs by a stepwise mechanism, namely a double Mukaiyama-type Michael addition rather than a concerted [4+2] cycloaddition and thus produces the exo product as the major isomer. For an example of a Diels-Alder reaction of the diene 6 with 2-methylcyclohexenone under Lewis acid catalysis to give mainly the endo adduct, see: a) M. Ge, B. M. Stoltz, E. J. Corey, Org. Lett. 2000, 2, 1927; since the endo isomer is the minor isomer in our case, we favor the double Michael process. For examples of Mukaiyama Michael additions, see: b) K. Narasaki, K. Soai. T. Mukaiyama, Chem. Lett. 1974, 1223; c) D. A. Evans, K. A. Scheidt, J. N. Johnston, M. C. Willis, J. Am. Chem. Soc. 2001, 123, 4480; d) G. Desimoni, G. Faita, S. Filippone, M. Mella, M. G. Zampori, M. Zema, Tetrahedron 2001, 57, 10203; for examples of double Michael additions to produce [4+2] cycloadducts, see: e) M. E. Jung in Comprehensive Organic Synthesis, Vol. 4 (Ed.: B. M. Trost), Pergamon, Oxford, 1991, chap. 1.1, pp. 1-67 (especially pp. 30-32).
28. It should be pointed out that Diels and Alder just described the reaction of a diene and dienophile to give cyclohexene systems without implying any mechanistic detail and thus this reaction is a Diels-Alder reaction by their definition even if the mechanism is more likely stepwise than concerted.
29. 3 in toluene was used).
30. Hydrolysis of the silyl enol ether with tetrabutylammonium fluoride (TBAF) gave poor yields, presumably due to retro-Michael reactions.
31. We thank Dr. Saeed Khan for obtaining the X-ray crystal structures. CCDC-194419 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.can.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Centre, 12 Union Road, Cambridge CB21EZ, UK; Fax: (+ 44) 1223-336033; or deposit@ccdc.cam.ac.uk).
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37. S. Kim, J. H. Park, Synlett 1995, 163.