An enantioselective synthesis of cis perhydroisoquinoline LY235959

Journal of Organic Chemistry

Volumn 63, Issue 3, 1998, Pages 775-785

  Hansen, Marvin M ^a   Bertsch, Carl F ^a   Harkness, Allen R ^a   Huff, Bret E ^a   Hutchison, Darrell R ^a   Khau, Vien V ^a   LeTourneau, Michael E ^a   Martinelli, Michael J ^a   Misner, Jerry W ^a   Peterson, Barry C ^a   Rieck, John A ^a   Sullivan, Kevin A ^a   Wright, Ian G ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DECAHYDRO 6 PHOSPHONOMETHYL 3 ISOQUINOLINECARBOXYLIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; PANTOLACTONE;

ALKYLATION; ALZHEIMER DISEASE; ARTICLE; DRUG SYNTHESIS; MOLECULAR DYNAMICS; OXIDATION; RECEPTOR BLOCKING; STEREOCHEMISTRY; THERMODYNAMICS;

EID: 6844258209     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9717649     Document Type: Article

References (53)

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5. For reviews, see: (a) Nogradi, M. Stereoselective Synthesis; VCH: Weinheim, FRG, 1987; pp 266-274. (b) Helmchen, G.; Karge, R.; Weetman, J. In Modern Synthetic Methods 1986; Sheffold, R., Ed.; Springer-Verlag: New York, 1986; Vol. 4, pp 262-306. For recent work, see: (c) Busacca, C. A.; Meyers, A. I. J. Chem. Soc., Perkin Trans. 1 1991, 2299-2316 and ref 1 therein, (d) Maruoka, K.; Akakura, M.; Saito, S.; Ooi, T.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 6153-6158.
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7. For reviews, see: (a) Nogradi, M. Stereoselective Synthesis; VCH: Weinheim, FRG, 1987; pp 266-274. (b) Helmchen, G.; Karge, R.; Weetman, J. In Modern Synthetic Methods 1986; Sheffold, R., Ed.; Springer-Verlag: New York, 1986; Vol. 4, pp 262-306. For recent work, see: (c) Busacca, C. A.; Meyers, A. I. J. Chem. Soc., Perkin Trans. 1 1991, 2299-2316 and ref 1 therein, (d) Maruoka, K.; Akakura, M.; Saito, S.; Ooi, T.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 6153-6158.
8. For reviews, see: (a) Nogradi, M. Stereoselective Synthesis; VCH: Weinheim, FRG, 1987; pp 266-274. (b) Helmchen, G.; Karge, R.; Weetman, J. In Modern Synthetic Methods 1986; Sheffold, R., Ed.; Springer-Verlag: New York, 1986; Vol. 4, pp 262-306. For recent work, see: (c) Busacca, C. A.; Meyers, A. I. J. Chem. Soc., Perkin Trans. 1 1991, 2299-2316 and ref 1 therein, (d) Maruoka, K.; Akakura, M.; Saito, S.; Ooi, T.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 6153-6158.
9. For reviews, see: (a) Kagan, H. B.; Riant, O. Chem. Rev. (Washington, D.C.) 1992, 92, 1007-1019. (b) Deloux, L.; Srebnik, M. Chem. Rev. (Washington, D.C.) 1993, 93, 763-784. (c) Togni, A.; Venanzi, L. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 497-526. For recent work, see: (d) Evans, D. A.; Barnes, D. M. Tetrahedron Lett. 1997, 35, 57-58. (e) Corey, E. J.; Letavic, M. A. J. Am. Chem. Soc. 1995, 117, 9616-9617.
10. For reviews, see: (a) Kagan, H. B.; Riant, O. Chem. Rev. (Washington, D.C.) 1992, 92, 1007-1019. (b) Deloux, L.; Srebnik, M. Chem. Rev. (Washington, D.C.) 1993, 93, 763-784. (c) Togni, A.; Venanzi, L. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 497-526. For recent work, see: (d) Evans, D. A.; Barnes, D. M. Tetrahedron Lett. 1997, 35, 57-58. (e) Corey, E. J.; Letavic, M. A. J. Am. Chem. Soc. 1995, 117, 9616-9617.
11. For reviews, see: (a) Kagan, H. B.; Riant, O. Chem. Rev. (Washington, D.C.) 1992, 92, 1007-1019. (b) Deloux, L.; Srebnik, M. Chem. Rev. (Washington, D.C.) 1993, 93, 763-784. (c) Togni, A.; Venanzi, L. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 497-526. For recent work, see: (d) Evans, D. A.; Barnes, D. M. Tetrahedron Lett. 1997, 35, 57-58. (e) Corey, E. J.; Letavic, M. A. J. Am. Chem. Soc. 1995, 117, 9616-9617.
12. For reviews, see: (a) Kagan, H. B.; Riant, O. Chem. Rev. (Washington, D.C.) 1992, 92, 1007-1019. (b) Deloux, L.; Srebnik, M. Chem. Rev. (Washington, D.C.) 1993, 93, 763-784. (c) Togni, A.; Venanzi, L. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 497-526. For recent work, see: (d) Evans, D. A.; Barnes, D. M. Tetrahedron Lett. 1997, 35, 57-58. (e) Corey, E. J.; Letavic, M. A. J. Am. Chem. Soc. 1995, 117, 9616-9617.
13. For reviews, see: (a) Kagan, H. B.; Riant, O. Chem. Rev. (Washington, D.C.) 1992, 92, 1007-1019. (b) Deloux, L.; Srebnik, M. Chem. Rev. (Washington, D.C.) 1993, 93, 763-784. (c) Togni, A.; Venanzi, L. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 497-526. For recent work, see: (d) Evans, D. A.; Barnes, D. M. Tetrahedron Lett. 1997, 35, 57-58. (e) Corey, E. J.; Letavic, M. A. J. Am. Chem. Soc. 1995, 117, 9616-9617.
14. Poll, T.; Abdel Hady, A. F.; Karge, R.; Linz, G.; Weetman, J.; Helmchen, G. Tetrahedron Lett. 1989, 30, 5595-5598. See Supporting Information for a detailed procedure.
15. Finkelstein, H. Ber. 1910, 43, 1528.
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17. (b) For a review of asymmetric methods, see: Duthaler, R. O. Tetrahedron 1994, 50, 1539-1650.
18. (a) See ref 6a, pp 709-712.
19. (b) Albertson, N. F. J. Am. Chem. Soc. 1946, 68, 450-453.
20. DMI is a less toxic substitute for HMPA, see: Sakurai, H.; Kondo, F. J. Organomet. Chem. 1976; 117, 149-155. We thank Dr. Tom Britton for recommending this solvent.
21. 1H NMR spectra of acid 21, diol 15, and alcohol i. Equation presented it
22. 3N, see: Schreiber, S. L.; Claus, R. E.; Reagan, J. Tetrahedron Lett. 1982, 23, 3867-3870.
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24. For the Arbuzov reaction on a similar substrate, see ref 1c and Ornstein, P. L.; Augenstein, N. K.; Arnold, M. B. J. Org. Chem. 1994, 59, 7862-7869.
25. 13C NMR spectra were comparable to those reported in ref 1b.
26. Heating in aqueous barium hydroxide at 180°C is frequently used to racemize the natural amino acids, see: Greenstein, J. P.; Winitz, M. Chemistry of the Amino Acids; Wiley: New York, 1961; Volume 3.
27. Conformations shown in Figure 1 have not been minimized but are useful in rationalizing the observed results.
28. Zeiss, H. J. Org. Chem. 1991, 56, 1783-1788.
29. LY235959 (1) containing <1% epimer 20 which was prepared using a modification of the reported procedure. See ref 1.
30. 1H NMR spectral data of isomers 27 and 28 with analogous C-3 epimers reported by Ornstein also supports the stereochemical assignment: 27, C-3 proton a triplet at 4.70 ppm, J = 5 Hz; 28, C-3 proton a doublet at 5.21 ppm, J = 7 Hz. Compare with compounds 31a and 40 in ref 1b.
31. Such intermediates are presumably involved in the racemization of L-proline by treatment with acetic anhydride in refluxing acetic acid, see ref 14, p 2195.
32. Prepared from corresponding alcohol in 93% yield.
33. The aldehyde is sensitive to epimerization and should be kept cold and used without delay.
34. Schmidt U.; Griesser, H.; Leitenberger, V.; Lieberknecht, A.; Mangold, R.; Meyer, R.; Riedl, B. Synthesis 1992, 487.
35. 1H NMR spectrum of the crude product mixture.
36. For a recent review on the use of homogeneous catalysts in hydrogenation, see: Burk, M. J.; Gross, M. F.; Harper, T. G. P.; Kalberg, C. S.; Lee, J. R.; Martinez, J. P. Pure Appl. Chem. 1996, 68 (1), 37. See also: Scott, J. W.; Keith, D. D.; Nix, Jr., G.; Parrish, D. R.; Remington, S.; Roth, G. P.; Townsend, J. M.; Valentine, Jr., D., Yang, R. J. Org. Chem. 1981, 46, 5086.
37. For a recent review on the use of homogeneous catalysts in hydrogenation, see: Burk, M. J.; Gross, M. F.; Harper, T. G. P.; Kalberg, C. S.; Lee, J. R.; Martinez, J. P. Pure Appl. Chem. 1996, 68 (1), 37. See also: Scott, J. W.; Keith, D. D.; Nix, Jr., G.; Parrish, D. R.; Remington, S.; Roth, G. P.; Townsend, J. M.; Valentine, Jr., D., Yang, R. J. Org. Chem. 1981, 46, 5086.
38. 1H NMR. Ratio was determined by integral areas of the C-3 protons.
39. O'Donnell, M. J.; Boniece, J. M.; Earp, S. E. Tetrahedron Lett. 1978, 2641-2644. (b) O'Donnell, M. J.; Eckrich, T. M. Tetrahedron Lett. 1978, 4625-4628. (c) O'Donnell, M. J.; Wu, S. Tetrahedron: Asymmetry 1992, 3, 591-594.
40. O'Donnell, M. J.; Boniece, J. M.; Earp, S. E. Tetrahedron Lett. 1978, 2641-2644. (b) O'Donnell, M. J.; Eckrich, T. M. Tetrahedron Lett. 1978, 4625-4628. (c) O'Donnell, M. J.; Wu, S. Tetrahedron: Asymmetry 1992, 3, 591-594.
41. O'Donnell, M. J.; Boniece, J. M.; Earp, S. E. Tetrahedron Lett. 1978, 2641-2644. (b) O'Donnell, M. J.; Eckrich, T. M. Tetrahedron Lett. 1978, 4625-4628. (c) O'Donnell, M. J.; Wu, S. Tetrahedron: Asymmetry 1992, 3, 591-594.
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44. O'Donnell, M. J.; Wojciechowski, K. Synthesis 1984, 313-315.
45. 4, see: (a) Sasaki, N. A.; Hashimoto, C.; Potier, P. Tetrahedron Lett. 1987, 28, 6069-6072. (b) Levai, L.; Ritvay-Emandity, K. Ber. Dutsch. Chem. Ges. 1959, 92, 2775.
46. 4, see: (a) Sasaki, N. A.; Hashimoto, C.; Potier, P. Tetrahedron Lett. 1987, 28, 6069-6072. (b) Levai, L.; Ritvay-Emandity, K. Ber. Dutsch. Chem. Ges. 1959, 92, 2775.
47. 26 Both methods provided amide 39 which contained minor amounts of benzophenone; however, benzophenone did not interfere with the subsequent alkylation reaction and was removed at a later stage (see Supporting Information).
48. The low isolated yield of 1 is due to an inefficient crystallization.
49. The enantiomeric excess of 1 correlates to the diastereomer ratio of Diels-Alder adduct 9. The enantiomeric excess and diastereomeric purity were assigned by HPLC.
50. See ref 1b.
51. 1H NMR. An analytical sample was prepared by drying at 60°C under high vacuum.
52. 1H NMR. An analytical sample was prepared by drying at 60°C under high vacuum.
53. 1H NMR after subtracting for residual solvent.