A practical synthesis of (±)-α-isosparteine from a tetraoxobispidine core

Organic Letters

Volumn 7, Issue 21, 2005, Pages 4721-4724

  Blakemore, Paul R ^a   Kilner, Colin ^b   Norcross, Neil R ^b   Astles, Peter C ^c  

^a OREGON STATE UNIVERSITY   (United States)

^b UNIVERSITY OF LEEDS   (United Kingdom)

^c ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BISPIDINE; FUSED HETEROCYCLIC RINGS; MALONIC ACID DERIVATIVE; METHYLMALONIC ACID; SPARTEINE;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; STEREOISOMERISM; SYNTHESIS;

BICYCLO COMPOUNDS, HETEROCYCLIC; MALONATES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; SPARTEINE; STEREOISOMERISM;

EID: 27144522621     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol0519184     Document Type: Article

References (59)

1. Reviews: (a) Michael, J. P. Nat. Prod. Rep. 2003, 20, 458.
2. (b) Ohmiya, S.; Saito, K.; Murakoshi, I. In The Alkaloids; Cordell, G. A., Ed.; Academic Press: New York, 1995; Vol. 47, p 1. See also earlier reviews in the same series.
3. Biological activity: (a) Schmeller, T.; Wink, M. In Alkaloids: Biochemistry, Ecology, and Medicinal Applications; Roberts, M. F., Wink, M., Eds.; Plenum Press: New York, 1998; p 435.
4. (b) Seeger, R.; Neumann, H. G. Inst. Pharmakol. Toxikol. 1992, 132, 1577.
5. Leonard, N. J. In The Alkaloids; Manske, R. H. F., Ed.; Academic Press: New York, 1960; Vol. 7, p 253.
6. (-)-Sparteine (lupinidine), a cardiac stimulant easily extracted from the weed Scotch broom (Cytisus scoparius), was first isolated in 1851 by Stenhouse and its structure correctly elucidated 82 years later by Clemo and Raper; see: Clemo, G. R.; Raper, R. J. Chem. Soc. 1933, 644.
7. (-)-α-Isosparteine (genisteine) was first obtained semi-synthetically from (-)-sparteine but later found naturally occurring in Lupinus caudatus, see: Marion, L.; Turcotte, F.; Ouellet, J. Can. J. Chem. 1951, 22, 29.
8. (-)-β-Isosparteine has also been known as l-spartalupine and pusilline and occurs in a variety of Lupinus species; see: Greenhalgh, R.; Marion, L. Can. J. Chem. 1956, 34, 456.
9. 3, see: Galinovsky, F.; Knoth, P.; Fischer, W. Monatsh. Chem. 1955, 86, 1014.
10. (b) For isomerization by oxidation/reduction, see: Okamoto, Y.; Suzuki, K.; Kitayama, T.; Yuki, H.; Kageyama, H.; Miki, K.; Tanaka, N.; Kasai, N. J. Am. Chem. Soc. 1982, 104, 4618.
11. For a review of sparteine/alkyllithium reagent pairs in synthesis, see: Hoppe, D.; Hense, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 2282.
12. Recent representative synthetic applications of (-)-sparteine: (a) Vrancken, E.; Alexakis, A.; Mangeney, P. Eur. J. Org. Chem. 2005, 1354.
13. (b) Caupene, C.; Boudou, C.; Perrio, S.; Metzner, P, J. Org. Chem. 2005, 70, 2812.
14. (c) Kocienski, P. J.; Christopher, J. A.; Bell, R.; Otto, B. Synthesis 2005, 75.
15. (d) Martinez, M. M.; Hoppe, D. Org. Lett. 2004, 6, 3743.
16. (e) Bagdanoff, J. T.; Stoltz, B. M. Angew. Chem., Int. Ed. 2004, 43, 353.
17. (f) Metallinos, C.; Szillat, H.; Taylor, N. J.; Snieckus, V. Adv. Synth. Catal. 2003, 345, 370.
18. (g) Shintani, R.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 1057
19. Recent representative synthetic applications of (-)-α-isosparteine: (a) Allen, B. D.; Cintrat, J.-C.; Faucher, N.; Berthault, P.; Rousseau, B.; O'Leary, D. J. J. Am. Chem. Soc. 2005, 127, 412.
20. (b) Hodgson, D. M.; Galano, J.-M.; Christlieb, M. Tetrahedron 2003, 59, 9719.
21. (c) Muller, P.; Patrice, N.; Bernardinelli, G. Eur. J. Org. Chem. 2001, 21, 4137.
22. (d) Hodgson, D. M.; Cameron, I. D.; Christlieb, M.; Green, R.; Lee, G. P.; Robinson, L. A. J. Chem. Soc., Perkin Trans. 1 2001, 18, 2161.
23. O'Brien has introduced a (+)-sparteine surrogate derived from (-)-cytisine which goes some way to addressing this issue, see: (a) Dearden, M. J.; Firkin, C. R.; Hermet, J.-P. R.; O'Brien, P. J. Am. Chem. Soc. 2002, 124, 11870.
24. (b) Dearden, M. J.; McGrath, M. J.; O'Brien, P. J. Org. Chem. 2004, 69, 5789.
25. (+)-Sparteine has been obtained from natural (±)-lupanine by resolution followed by reduction, see: Ebner, T.; Eichelbaum, M.; Fischer, P.; Meese, C. O. Arch. Pharm. (Weinheim) 1989, 322, 399.
26. Syntheses of (±)-sparteine: (a) Leonard, N. J.; Beyler, R. E. J. Am. Chem. Soc. 1948, 70, 2298.
27. (b) Leonard, N. J.; Beyler, R. E. J. Am. Chem. Soc. 1950, 72, 1316.
28. (c) Clemo, G. R.; Raper, R.; Short, W. S. J. Chem. Soc. 1949, 663.
29. (d) van Tamelen, E. E.; Foltz, R. L. J. Am. Chem. Soc. 1969, 91, 7372.
30. (e) Bohlmann, F.; Müller, H.-J.; Schumann Chem. Ber. 1973, 106, 3026.
31. (f) Takatsu, N.; Noguchi, M.; Ohmiya, S.; Otomasu, H. Chem. Pharm. Bull. 1987, 35, 4990.
32. (g) Wanner, M. J.; Koomen, G.-J. J. Org. Chem. 1996, 61, 5581.
33. (h) Butler, T.; Fleming, I.; Gonsior, S.; Kim, B.-H.; Sung, A.-Y.; Woo, H.-G. Org. Biomol. Chem. 2005, 3, 1557.
34. Syntheses of (±)-α-isosparteine: (a) Sorm, F.; Keil, B. Collect. Czech. Chem. Commun. 1948, 13, 544.
35. (b) Tsuda, K.; Sato, T. Chem. Pharm. Bull. 1954, 2, 190.
36. (c) Oinuma, H.; Dan, S.; Kakisawa, H. J. Chem. Soc., Perkin Trans. 1 1990, 2593. See also ref 13b.
37. Syntheses of (±)-β-isosparteine: Carmack, M.; Douglas, B.; Martin, E. W.; Suss, H. J. Am. Chem. Soc. 1955, 77, 4435. See also refs 14b and 13 g.
38. Notable exceptions include the very first synthesis of sparteine and α-isosparteine by Leonard and Beyler (two steps, ref 13ab) and the elegant three-step approach to α-isosparteine by Kakisawa et al (ref 14c).
39. The following enantioselective syntheses by Aubé and O'Brien could each be used in principle to prepare either (+)- or (-)-sparteine: (a) Smith, B. T.; Wendt, J. A.; Aubé, J. Org. Lett. 2002, 4, 2577.
40. (b) Hermet, J.-P. R.; McGrath, M. J.; O'Brien, P.; Porter, D. W.; Gilday, J. Chem. Commun. 2004, 1830.
41. Speckamp and Hiemstra have made seminal contributions in this area; see: Ostendorf, M.; Romagnoli, R.; Pereiro, I. C.; Roos, E. C.; Moolenaar, M. J.; Speckamp, W. N.; Hiemstra, H. Tetrahedron: Asymmetry 1997, 8, 1773.
42. Review: Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
43. By tetraoxobispidine we imply 2,4,6,8-tetraoxo-3,7-diazabicyclo-[3.3.1] nonane. A substructure search of Scifinder Scholar retrieved 188 examples of this ring system mono- or disubstituted at position 9.
44. The Guareschi condensation is a Knoevenagel-type three-component coupling reaction between a cyanoacetate, a carbonyl compound and ammonia; the initially generated α,α′-dicyanoglutarimides cyclize to tetraoxobispidines upon treatment with sulfuric acid; see: (a) Guareschi, I. Gazz. Chim. Ital. 1919, 49, 126.
45. (b) Kon, G. A. R.; Thorpe, J. F. J. Chem. Soc. 1919, 686.
46. (c) Vogel, A. I. J. Chem. Soc. 1934, 1758.
47. Guareschi imides have been used as precursors to bispidines having antiarrhythmic properties; see: Schön, U.; Antel, J.; Brückner, R.; Messinger, J. J. Med. Chem. 1998, 41, 318.
48. Guthzeit, J. J. Prakt. Chem. 1902, 2, 11.
49. Acidic hydrolysis of 1,1,3,3-tetracyanopropane failed to produce bisimide 6. For the preparation of 1,1,3,3-tetracyanopropane, see: Bell, R. A.; Brown, B. E.; Duarte, M.; Howard-Lock, H. E.; Lock, C. J. L. Can. J. Chem. 1987, 65, 261.
50. Gogoll, A.; Johansson, C.; Axén, A.; Grennberg, H. Chem. Eur. J. 2001, 7, 396.
51. Whether the hydroxyl groups in 8 are both exo or both endo has not been determined; however, we presume that they are configurated endo as illustrated based on steric considerations.
52. Schwab, P. E.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996, 118, 100.
53. It is worth noting that tetracycle 9 could potentially be generated in enantioenriched form by kinetic resolution of 8 using a chiral metathesis catalyst. For an example of enantioselective olefin metathesis, see: van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda, A. H. J. Am. Chem. Soc. 2002, 124, 4954.
54. 2-symmetry (see the Supporting Information). The apparent discrepancy between solution- and solid-state structures for 9 is explicable by a number of arguments. Either a symmetric anomer of 9 equilibrates to the asymmetric form only upon crystallization or the two (indistinguishable) asymmetric forms for 9 are in rapid dynamic equilibrium in solution. A third possibility, that NMR is a poor indicator of molecular symmetry for this molecule, seems less likely.
55. Louie, J.; Bielawski, C. W.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 11312.
56. 13b mp 132.5-133.5°C (EtOH)].
57. 13C NMR data for dl-1 prepared from 7 were essentially identical to those reported for l-1 by Galasso et al.; see: Galasso, V.; Asaro, F.; Berti, F.; Kovac, B.; Habus, I.; Sacchetti, A. Chem. Phys. 2003, 294, 155.
58. Harrison and O'Brien have observed that related bispidine-type acyl iminium ions experience nucleophilic attack exclusively from their open exo faces; see: Harrison, J. R.; O'Brien, P. Tetrahedron Lett. 2000, 41, 6167.
59. Strategic reversal in allylation and reduction of 7 leads in principle to β-isosparteine stereochemistry. Isomerization of β-isosparteine to sparteine is known; see ref 15.