Asymmetric deprotonation by BuLi/(-)-sparteine: Convenient and highly enantioselective syntheses of (S)-2-aryl-Boc-pyrrolidines

Journal of the American Chemical Society

Volumn 118, Issue 4, 1996, Pages

  Wu, Shengde ^a   Lee, Steven ^a   Beak, Peter ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

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EID: 3643095323     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (49)

1. For recent summaries see: Knochel, P. Angew. Chem., Int. Ed. Engl. 1992, 31, 1459. Aggarawal, J. K. Angew. Chem., Int. Ed. Engl. 1994, 33, 175. For recent reports and leading references see: (a) Carstens, A: Hoppe, D. Titrahedron 1994, 50, 6097. (b) Thayumanavan, S.; Lee, S ; Liu, C.; Beak, P. J. Am. Chem. Soc. 1994, 116, 9755.
2. For recent summaries see: Knochel, P. Angew. Chem., Int. Ed. Engl. 1992, 31, 1459. Aggarawal, J. K. Angew. Chem., Int. Ed. Engl. 1994, 33, 175. For recent reports and leading references see: (a) Carstens, A: Hoppe, D. Titrahedron 1994, 50, 6097. (b) Thayumanavan, S.; Lee, S ; Liu, C.; Beak, P. J. Am. Chem. Soc. 1994, 116, 9755.
3. For recent summaries see: Knochel, P. Angew. Chem., Int. Ed. Engl. 1992, 31, 1459. Aggarawal, J. K. Angew. Chem., Int. Ed. Engl. 1994, 33, 175. For recent reports and leading references see: (a) Carstens, A: Hoppe, D. Titrahedron 1994, 50, 6097. (b) Thayumanavan, S.; Lee, S ; Liu, C.; Beak, P. J. Am. Chem. Soc. 1994, 116, 9755.
4. For recent summaries see: Knochel, P. Angew. Chem., Int. Ed. Engl. 1992, 31, 1459. Aggarawal, J. K. Angew. Chem., Int. Ed. Engl. 1994, 33, 175. For recent reports and leading references see: (a) Carstens, A: Hoppe, D. Titrahedron 1994, 50, 6097. (b) Thayumanavan, S.; Lee, S ; Liu, C.; Beak, P. J. Am. Chem. Soc. 1994, 116, 9755.
5. Beak, P , Kerrick, S. T.; Wu, S.; Chu, J. J. Am. Chem Soc., 1994, 116, 3231.
6. Dieter has recently reported arylations of 2-lithio-Boc-pyrrolidines by a copper-catalyzed palladium coupling reaction with aryl iodides: Dieter, R. K.; Li S. Tetrahedron Lett. 1995, 36, 3613. An earlier report from Dieter's laboratories showed that the enantiointegrity of the 2-lithio-Boc-pyrrolidine was lost on conversion to the copper derivative and addition to α,β unsaturated ketones. Dieter, R. K.; Alexander, C. W., Syn. lett. 1993, 407.
7. Dieter has recently reported arylations of 2-lithio-Boc-pyrrolidines by a copper-catalyzed palladium coupling reaction with aryl iodides: Dieter, R. K.; Li S. Tetrahedron Lett. 1995, 36, 3613. An earlier report from Dieter's laboratories showed that the enantiointegrity of the 2-lithio-Boc-pyrrolidine was lost on conversion to the copper derivative and addition to α,β unsaturated ketones. Dieter, R. K.; Alexander, C. W., Syn. lett. 1993, 407.
8. Chiral 2-substituted pyrrolidines, which occur widely as natural products and are useful as chiral auxiliaries, chiral bases, and chiral ligands, are worthy synthetic targets. For summaries and reviews see: Hart, D. J. Alkaloids: Chemical and Biological Perspectives: Pelletier, S. W., Ed.; Wiley New York, 1988; Vol. 6, Chapter 3. Hiemstra, H; Speckamp, W. N. The Alkaloids, Brossi A., Ed.; Academic Press: New York, 1988. Whitesell, J. K. Chem. Rev 1989, 89, 1581. Tomioka, K. Synthesis, 1990, 541.
9. Chiral 2-substituted pyrrolidines, which occur widely as natural products and are useful as chiral auxiliaries, chiral bases, and chiral ligands, are worthy synthetic targets. For summaries and reviews see: Hart, D. J. Alkaloids: Chemical and Biological Perspectives: Pelletier, S. W., Ed.; Wiley New York, 1988; Vol. 6, Chapter 3. Hiemstra, H; Speckamp, W. N. The Alkaloids, Brossi A., Ed.; Academic Press: New York, 1988. Whitesell, J. K. Chem. Rev 1989, 89, 1581. Tomioka, K. Synthesis, 1990, 541.
10. Chiral 2-substituted pyrrolidines, which occur widely as natural products and are useful as chiral auxiliaries, chiral bases, and chiral ligands, are worthy synthetic targets. For summaries and reviews see: Hart, D. J. Alkaloids: Chemical and Biological Perspectives: Pelletier, S. W., Ed.; Wiley New York, 1988; Vol. 6, Chapter 3. Hiemstra, H; Speckamp, W. N. The Alkaloids, Brossi A., Ed.; Academic Press: New York, 1988. Whitesell, J. K. Chem. Rev 1989, 89, 1581. Tomioka, K. Synthesis, 1990, 541.
11. Chiral 2-substituted pyrrolidines, which occur widely as natural products and are useful as chiral auxiliaries, chiral bases, and chiral ligands, are worthy synthetic targets. For summaries and reviews see: Hart, D. J. Alkaloids: Chemical and Biological Perspectives: Pelletier, S. W., Ed.; Wiley New York, 1988; Vol. 6, Chapter 3. Hiemstra, H; Speckamp, W. N. The Alkaloids, Brossi A., Ed.; Academic Press: New York, 1988. Whitesell, J. K. Chem. Rev 1989, 89, 1581. Tomioka, K. Synthesis, 1990, 541.
12. For our report of the corresponding racemic reaction see: Beak, P.; Wu, S., Yum, E. K.; Jun, Y. M. J. Org. Chem. 1994, 59, 276. For formation of pyrrolidines by cyclization through addition of an α-lithioamine to a double bond see: Coldham, I.; Hufton, R. Tetrahedron Lett 1995, 36, 2157.
13. For our report of the corresponding racemic reaction see: Beak, P.; Wu, S., Yum, E. K.; Jun, Y. M. J. Org. Chem. 1994, 59, 276. For formation of pyrrolidines by cyclization through addition of an α-lithioamine to a double bond see: Coldham, I.; Hufton, R. Tetrahedron Lett 1995, 36, 2157.
14. (a) Burgess, L. E., Meyers, A. I. J. Org. Chem. 1992, 57, 1656.
15. (b) The original source for the determination of the absolute configuration of 2-phenylpyrrolidine was by correlation with the absolute configuration of 2-phenylglutaric acid. Morlacchi, F.; Losacco, V.; Tortorella, V. Gazz. Chim. Ital. 1975, 105, 349.
16. Higashiyama, K., Inoue, H ; Takahashi, H. Tetrahedron 1994, 50, 1083.
17. Manescalchi, F., Nardi, A. R.; Savoia, D. Tetrahedron Lett. 1994, 35, 2775.
18. Ozawa, F., Hayashi, T. J. Organomet. Chem. 1992, 428, 267.
19. Willoughby, C. A ; Buchwald, S. L J. Org. Chem. 1994, 116, 11703.
20. The yields were not optimized, and trace amounts of elimination products were observed. The alternative approach with 1-bromo-3-chloropropane and Boc-phenylmethylamine under the same alkylation conditions gave less than 20%of 1 with the elimination product. N-Boc-N-allyl-N-benzylamine, as the major product.
21. Pirkle, W. H.; McCune, J. E. J. Chromatogr. 1989, 479, 471, 271.
22. A limitation of pentane is that 2-7 have lower solubilities at lower temperatures. In toluene, these compounds are soluble at -78 °C.
23. The racemic pyrrolidine of 12 has been reported. (a) Maryanoff, B. E.; Vaught, J. L.; Shank, R, P.; McComsey, D. F., Costanzo, M. J.; Nortey, S. O. J. Med. Chem. 1990, 33, 2793. (b) Elslager, E. F.; Johnson, J. L.; Werbel, L. M. J. Med. Chem. 1981, 24, 140. (c) Elslager, E. F.; Clarke, J.; Werbel, L. M.; Worth, D. F.; Davoll, J. J. Med. Chem. 1972, 15, 827
24. The racemic pyrrolidine of 12 has been reported. (a) Maryanoff, B. E.; Vaught, J. L.; Shank, R, P.; McComsey, D. F., Costanzo, M. J.; Nortey, S. O. J. Med. Chem. 1990, 33, 2793. (b) Elslager, E. F.; Johnson, J. L.; Werbel, L. M. J. Med. Chem. 1981, 24, 140. (c) Elslager, E. F.; Clarke, J.; Werbel, L. M.; Worth, D. F.; Davoll, J. J. Med. Chem. 1972, 15, 827
25. The racemic pyrrolidine of 12 has been reported. (a) Maryanoff, B. E.; Vaught, J. L.; Shank, R, P.; McComsey, D. F., Costanzo, M. J.; Nortey, S. O. J. Med. Chem. 1990, 33, 2793. (b) Elslager, E. F.; Johnson, J. L.; Werbel, L. M. J. Med. Chem. 1981, 24, 140. (c) Elslager, E. F.; Clarke, J.; Werbel, L. M.; Worth, D. F.; Davoll, J. J. Med. Chem. 1972, 15, 827
26. The racemic pyrrolidine of 13 has been reported. (a) Viswanathan, N.; Sidhaye, A. R. Tetrahedron Lett. 1979, 52, 5025. (b) Seeman, J. I.; Secor, H. V.; Forrest, G. J. Labelled Compd. Radiopharm, 1979, 16, 387.
27. The racemic pyrrolidine of 13 has been reported. (a) Viswanathan, N.; Sidhaye, A. R. Tetrahedron Lett. 1979, 52, 5025. (b) Seeman, J. I.; Secor, H. V.; Forrest, G. J. Labelled Compd. Radiopharm, 1979, 16, 387.
28. The racemic pyrrolidine of 14 has been reported. (a) See ref. 15a. (b) Severin, T.; Poehlmann, H. Chem. Ber. 1977, 110, 491.
29. The racemic pyrrolidine of 14 has been reported. (a) See ref. 15a. (b) Severin, T.; Poehlmann, H. Chem. Ber. 1977, 110, 491.
30. The racemic pyrrolidine of 15 has been reported. (a) Ferrand, G.; Barbanton, J.; Depin, J.; Chavernac, G. CA Patent 1327364, 1995; Chem. Abstr. 1995, 122, 31318. (b) Wettlaufer, D. G.; Nemoto, P. A. US Patent 5338739, 1994; Chem. Abstr. 1994, 121, 280538. (c) Ferrand, G.; Barbanton, J.; Depin, J.; Chavernac, G. EP Patent 360685, 1990; Chem. Abstr. 1990, 113, 115096.
31. The racemic pyrrolidine of 15 has been reported. (a) Ferrand, G.; Barbanton, J.; Depin, J.; Chavernac, G. CA Patent 1327364, 1995; Chem. Abstr. 1995, 122, 31318. (b) Wettlaufer, D. G.; Nemoto, P. A. US Patent 5338739, 1994; Chem. Abstr. 1994, 121, 280538. (c) Ferrand, G.; Barbanton, J.; Depin, J.; Chavernac, G. EP Patent 360685, 1990; Chem. Abstr. 1990, 113, 115096.
32. The racemic pyrrolidine of 15 has been reported. (a) Ferrand, G.; Barbanton, J.; Depin, J.; Chavernac, G. CA Patent 1327364, 1995; Chem. Abstr. 1995, 122, 31318. (b) Wettlaufer, D. G.; Nemoto, P. A. US Patent 5338739, 1994; Chem. Abstr. 1994, 121, 280538. (c) Ferrand, G.; Barbanton, J.; Depin, J.; Chavernac, G. EP Patent 360685, 1990; Chem. Abstr. 1990, 113, 115096.
33. The racemic pyrrolidines of 16 and 17 have been reported. Grande, M. T.; Sollhuber, M. M. Chem. Scr. 1988, 28, 411.
34. (a) The enantioenriched pyrrolidine of 20 has been reported in ref. 7. The racemic pyrrolidine of 20 has been reported: (b) Wettlaufer, D. G.; Nemoto, P. A. US Patent 5338739, 1994; Chem. Abstr. 1994, 121, 280538. (c) Viswanathan, N.; Sidhaye, A. R. Tetrahedron Lett. 1979, 52, 5025.
35. (a) The enantioenriched pyrrolidine of 20 has been reported in ref. 7. The racemic pyrrolidine of 20 has been reported: (b) Wettlaufer, D. G.; Nemoto, P. A. US Patent 5338739, 1994; Chem. Abstr. 1994, 121, 280538. (c) Viswanathan, N.; Sidhaye, A. R. Tetrahedron Lett. 1979, 52, 5025.
36. (a) The enantioenriched pyrrolidine of 20 has been reported in ref. 7. The racemic pyrrolidine of 20 has been reported: (b) Wettlaufer, D. G.; Nemoto, P. A. US Patent 5338739, 1994; Chem. Abstr. 1994, 121, 280538. (c) Viswanathan, N.; Sidhaye, A. R. Tetrahedron Lett. 1979, 52, 5025.
37. The source of the low enantiomeric excess with 10 has not been determined. Equilibration by a ring-opening ring sequence promoted by the p-methoxy group is possible. It is also noted that a p-methoxy group has been reported to have a deleterious effect on a lateral lithiation. Clark, R. D., Muchowski, J. M., Fisher, L. E ; Flippin, L A.; Nephe, D B.; Souchet, M. Synthesis 1991, 871
38. 2
39. 1
40. Schlosser and Limat have found that deprotonation of benzylmethyl-Boc-amine with s-BuLi/(-)-sparteine is highly asymmetric but that race-mization is rapid and that the configuration of the subsequent asymmetric substitution is highly solvent dependent. Schlosser, M. Private communication. June 1994. Contribution by M. Schlosser and D. Limat at the Chiral-2 Workshop in Gwatt. March 1995. Simposium Brochure, p A-4
41. Hoppe, D.; Paetau, M.; Hintze, F. Angew. Chem., Int. Ed. Engl. 1993, 32, 394.
42. Beak, P , Du, H. J. Am. Chem. Soc. 1993, 115, 2516.
43. Kaiser, B., Hoppe, D Angew. Chem., Int. Ed. Engl. 1995, 34, 323.
44. Similar results were observed in toluene and in pentane.
45. The possibility that the tin lithium exchange and the deprotonation do not produce the same organolithium intermediate with respect to complexation with (-)-sparteine on the time scale of the experiment is more difficult to rule out, however.
46. The cyclization to form six-membered rings was attempted, but we were unable to obtain high ee's and good yields.
47. Suffert, J. J Org. Chem. 1989, 54, 509.
48. Compound 19 was not characterized in detail due to the impractical yield.
49. Compound 20 was not characterized in detail due to the low ee