Chiral organolithium complexes: The structure of β-lithiated β-phenylcarboxamides and the mechanism of asymmetric substitution in the presence of (-)-sparteine

Journal of the American Chemical Society

Volumn 118, Issue 46, 1996, Pages 11391-11398

  Gallagher, Donald J ^a   Du, Hua ^a   Long, Scott A ^a   Beak, Peter ^a  

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

Author keywords

[No Author keywords available]

Indexed keywords

ORGANOLITHIUM COMPOUND; SPARTEINE;

ARTICLE; COMPLEX FORMATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; NUCLEAR MAGNETIC RESONANCE; THERMODYNAMICS;

EID: 0029968950     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja962430o     Document Type: Article

References (49)

1. Hoppe, D.; Hintze, F.; Tebben, P.; Paetow, M.; Aherns, H.; Schwerdtfeger, J.; Sommerfeld, P.; Haller, J.; Guarnieri, W.; Kolczewski, S.; Hense, T.; Hoppe, I. Pure & Appl. Chem. 1994, 66, 1479. Knochel, P. Angew. Chem., Int. Ed. Engl. 1992, 31, 1459.
2. Hoppe, D.; Hintze, F.; Tebben, P.; Paetow, M.; Aherns, H.; Schwerdtfeger, J.; Sommerfeld, P.; Haller, J.; Guarnieri, W.; Kolczewski, S.; Hense, T.; Hoppe, I. Pure & Appl. Chem. 1994, 66, 1479. Knochel, P. Angew. Chem., Int. Ed. Engl. 1992, 31, 1459.
3. Park, Y. S.; Boys, M. L.; Beak, P. J. Am. Chem. Soc. 1996, 118, 3757. Beak, P.; Kerrick, S. T.; Wu, S.; Chu, J. J. Am. Chem. Soc. 1994, 116, 3231.
4. Park, Y. S.; Boys, M. L.; Beak, P. J. Am. Chem. Soc. 1996, 118, 3757. Beak, P.; Kerrick, S. T.; Wu, S.; Chu, J. J. Am. Chem. Soc. 1994, 116, 3231.
5. Muci, A. R.; Campos, K. R.; Evans, D. A. J. Am. Chem. Soc. 1995, 117, 9075.
6. Tsukazaki, M.; Tinkl, M.; Roglans, A.; Chapell, B. J.; Taylor, N. J.; Snieckus, V. J. Am. Chem. Soc. 1996, 118, 685.
7. Beak, P.; Du, H. J. Am. Chem. Soc. 1993, 115, 2516.
8. Lutz, G. P.; Du, H.; Gallagher, D. J.; Beak, P. J. Org. Chem. 1996, 61, 4542.
9. Beak, P.; Basu, A.; Gallagher, D. J.; Park, Y. S.; Thayumanavan, S. Acc. Chem. Res., in press.
10. For examples of asymmetric deprotonation reactions, see: (a) Hoppe, D.; Zchage, O. Angew. Chem., Int. Ed. Engl. 1989, 28, 69. (b) Hoppe, D.; Hintze, F.; Tebben, P. Angew. Chem., Int. Ed. Engl. 1990, 29, 1422. (c) Kerrick, S. T.; Beak, P. J. Am. Chem. Soc. 1991, 113, 9708. (d) Hoppe, D.; Paetow, M.; Hintze, F. Angew. Chem., Int. Ed. Engl. 1993, 32, 394. (e) Wu, S.; Lee, S. P.; Beak, P. J. Am. Chem. Soc. 1996, 118, 1575.
11. For examples of asymmetric deprotonation reactions, see: (a) Hoppe, D.; Zchage, O. Angew. Chem., Int. Ed. Engl. 1989, 28, 69. (b) Hoppe, D.; Hintze, F.; Tebben, P. Angew. Chem., Int. Ed. Engl. 1990, 29, 1422. (c) Kerrick, S. T.; Beak, P. J. Am. Chem. Soc. 1991, 113, 9708. (d) Hoppe, D.; Paetow, M.; Hintze, F. Angew. Chem., Int. Ed. Engl. 1993, 32, 394. (e) Wu, S.; Lee, S. P.; Beak, P. J. Am. Chem. Soc. 1996, 118, 1575.
12. For examples of asymmetric deprotonation reactions, see: (a) Hoppe, D.; Zchage, O. Angew. Chem., Int. Ed. Engl. 1989, 28, 69. (b) Hoppe, D.; Hintze, F.; Tebben, P. Angew. Chem., Int. Ed. Engl. 1990, 29, 1422. (c) Kerrick, S. T.; Beak, P. J. Am. Chem. Soc. 1991, 113, 9708. (d) Hoppe, D.; Paetow, M.; Hintze, F. Angew. Chem., Int. Ed. Engl. 1993, 32, 394. (e) Wu, S.; Lee, S. P.; Beak, P. J. Am. Chem. Soc. 1996, 118, 1575.
13. For examples of asymmetric deprotonation reactions, see: (a) Hoppe, D.; Zchage, O. Angew. Chem., Int. Ed. Engl. 1989, 28, 69. (b) Hoppe, D.; Hintze, F.; Tebben, P. Angew. Chem., Int. Ed. Engl. 1990, 29, 1422. (c) Kerrick, S. T.; Beak, P. J. Am. Chem. Soc. 1991, 113, 9708. (d) Hoppe, D.; Paetow, M.; Hintze, F. Angew. Chem., Int. Ed. Engl. 1993, 32, 394. (e) Wu, S.; Lee, S. P.; Beak, P. J. Am. Chem. Soc. 1996, 118, 1575.
14. For examples of asymmetric deprotonation reactions, see: (a) Hoppe, D.; Zchage, O. Angew. Chem., Int. Ed. Engl. 1989, 28, 69. (b) Hoppe, D.; Hintze, F.; Tebben, P. Angew. Chem., Int. Ed. Engl. 1990, 29, 1422. (c) Kerrick, S. T.; Beak, P. J. Am. Chem. Soc. 1991, 113, 9708. (d) Hoppe, D.; Paetow, M.; Hintze, F. Angew. Chem., Int. Ed. Engl. 1993, 32, 394. (e) Wu, S.; Lee, S. P.; Beak, P. J. Am. Chem. Soc. 1996, 118, 1575.
15. In this paper enantiomeric ratios (er) are reported as a measure of the enantioselectivity of the reaction.
16. The lower yield of 16 in this experiment was accompanied by isolation of amide 1 in 32% yield, suggesting some protonation of 15 may have occurred during this reaction.
17. Schlosser and co-workers have shown that an asymmetric deprotonation/epimerization/asymmetric substitution process is operative during the lithiation of N-Boc-N-methylbenzylamine. Schlosser, M.; Limat, D. J. Am. Chem. Soc. 1995, 117, 12342.
18. (a) We have used this methodology for the detection of a diastereoselective deprotonation. Lutz, G. P.; Wallin, A. P.; Kerrick, S. T.; Beak, P. J. Org. Chem. 1991, 56, 4938.
19. (b) For an application to an asymmetric sulfur dipole-stabilized carbanionic reaction, see: Kaiser, B.; Hoppe, D. Angew. Chem., Int. Ed. Engl. 1995, 34, 323.
20. Relatively small differences in an N-Me vs N-Et group have been found to influence an asymmetric reaction: Shimaro, M.; Meyers, A. I. J. Org. Chem. 1995, 60, 7445.
21. The lack of observable splitting prevents the determination of the aggregation state of this benzylic organolithium species. Splitting between the lithium and carbon atoms of benzylic lithium species is very difficult to observe. Fraenkel, G.; Martin, K. V. J. Am. Chem. Soc. 1995, 117, 10336.
22. 13C NMR spectra of 15 and 15/4 are provided as Supporting Information.
23. 13C NMR shifts of (7-phenylnorbornyl)lithium and (7-phenylnorbornyl)potassium relative to 7-phenylnorbornane. Peoples, P. R.; Grutzner, J. B J. Am. Chem. Soc. 1980, 102, 4709.
24. We have used a similar analysis in the study of N,N-diisopropyl-2-methyl-3-phenyl-3-lithiopropionamide. See ref 12a.
25. 8 solution contained in a 5 mm tube coaxially anchored in the 10 mm NMR tube containing the sample solutions.
26. It proved to be experimentally challenging to shim these samples because of the presence of the coaxially-held standard tube and also because some precipitation often occurred in the sample during the acquisition of the NMR spectra.
27. Maetzke, T.; Hidber, C. P.; Seebach, D. J. Am. Chem. Soc. 1990, 112, 8248. Maetzke, T.; Seebach, D. Organometallics 1990, 9, 3032.
28. Maetzke, T.; Hidber, C. P.; Seebach, D. J. Am. Chem. Soc. 1990, 112, 8248. Maetzke, T.; Seebach, D. Organometallics 1990, 9, 3032.
29. For studies of alkoxide aggregation, see: Jackman, L. M.; Rakiewicz, E. F.; Benesi, A. J. J. Am. Chem. Soc. 1991, 113, 4101. McGarrity, J. F.; Ogle, C. A. J. Am. Chem. Soc. 1985, 107, 1805.
30. For studies of alkoxide aggregation, see: Jackman, L. M.; Rakiewicz, E. F.; Benesi, A. J. J. Am. Chem. Soc. 1991, 113, 4101. McGarrity, J. F.; Ogle, C. A. J. Am. Chem. Soc. 1985, 107, 1805.
31. Basu, A.; Gallagher, D. J.; Beak, P. J. Org. Chem. 1996, 61, 5718.
32. Hoffmann, R. W.; Julius, M.; Chemla, F.; Ruhland, T.; Frezen, G. Tetrahedron 1994, 50, 6049. Hoffmann, R. W.; Rühl, T.; Chemla, F.; Zahneisen, T. Liebigs Ann. Chem. 1992, 719. Hirsch, R.; Hoffmann, R. W. Chem. Ber. 1992, 125, 975.
33. Hoffmann, R. W.; Julius, M.; Chemla, F.; Ruhland, T.; Frezen, G. Tetrahedron 1994, 50, 6049. Hoffmann, R. W.; Rühl, T.; Chemla, F.; Zahneisen, T. Liebigs Ann. Chem. 1992, 719. Hirsch, R.; Hoffmann, R. W. Chem. Ber. 1992, 125, 975.
34. Hoffmann, R. W.; Julius, M.; Chemla, F.; Ruhland, T.; Frezen, G. Tetrahedron 1994, 50, 6049. Hoffmann, R. W.; Rühl, T.; Chemla, F.; Zahneisen, T. Liebigs Ann. Chem. 1992, 719. Hirsch, R.; Hoffmann, R. W. Chem. Ber. 1992, 125, 975.
35. Interpretation of the reverse observation cannot be made. If the same enantiomeric ratio is observed between the two reactions, no definitive conclusion can be drawn.
36. The temperature of each reaction flask was monitored by a Teflon-coated internal thermocouple. Care was taken to make certain that the internal temperature of each solution was the same at the time of reaction with the electrophile.
37. We estimate the error in enantiomeric ratio determination by CSP HPLC to be 2%.
38. 3OD, and the product 16 was analyzed for deuterium content. No deuterium incorporation was found, indicating that in situ lithiation of the product is not the cause of the different er values.
39. Zschage, O.; Hoppe, D. Tetrahedron 1992, 48, 5657.
40. In addition, we have also performed the lithiation of 1 at higher concentrations which results in the formation of precipitates. The mixture was filtered at -78 °C, and the solution and solid reacted separately with TMSCI. Generally high enantiomeric excesses (70-88% ee) in the products were found from both the solution and solid, indicating that selective precipitation is not the source of enantioselectivity in this reaction.
41. Noyori, R.; Tokunaga, M.; Kitamura, M. Bull. Chem. Soc. Jpn. 1995, 68, 36.
42. The reactivity in this potential pathway is governed by the Curtin-Hammett principle. Curtin, D. Y. Rec. Chem. Prog. 1954, 15, 111. For a full treatment of Curtin-Hammett-Winstein-Holness kinetics, see: Seeman, J. I. Chem. Rev. 1983, 83, 83.
43. The reactivity in this potential pathway is governed by the Curtin-Hammett principle. Curtin, D. Y. Rec. Chem. Prog. 1954, 15, 111. For a full treatment of Curtin-Hammett-Winstein-Holness kinetics, see: Seeman, J. I. Chem. Rev. 1983, 83, 83.
44. For cases in which the enantioselectivity reflects differences in ground state energies of diastereomeric organolithium complexes, see: Klute, W.; Kruger, M.; Hoffman, R. W. Chem. Ber. 1996, 129, 633.; Basu, A., Beak, P. J. Am. Chem. Soc. 1996, 188, 1575. For cases in which the enantioselectivity reflects the difference in transition state energies, ΔΔG‡, see: Hoffmann, R. W.; Rühl, T.; Harbach, J. Liebigs Ann. Chem. 1992, 725. Thayumanaman, S.; Lee, S. P.; Liu, C.; Beak, P. J. Am. Chem. Soc. 1994, 116, 9755.
45. For cases in which the enantioselectivity reflects differences in ground state energies of diastereomeric organolithium complexes, see: Klute, W.; Kruger, M.; Hoffman, R. W. Chem. Ber. 1996, 129, 633.; Basu, A., Beak, P. J. Am. Chem. Soc. 1996, 188, 1575. For cases in which the enantioselectivity reflects the difference in transition state energies, ΔΔG‡, see: Hoffmann, R. W.; Rühl, T.; Harbach, J. Liebigs Ann. Chem. 1992, 725. Thayumanaman, S.; Lee, S. P.; Liu, C.; Beak, P. J. Am. Chem. Soc. 1994, 116, 9755.
46. For cases in which the enantioselectivity reflects differences in ground state energies of diastereomeric organolithium complexes, see: Klute, W.; Kruger, M.; Hoffman, R. W. Chem. Ber. 1996, 129, 633.; Basu, A., Beak, P. J. Am. Chem. Soc. 1996, 188, 1575. For cases in which the enantioselectivity reflects the difference in transition state energies, ΔΔG‡, see: Hoffmann, R. W.; Rühl, T.; Harbach, J. Liebigs Ann. Chem. 1992, 725. Thayumanaman, S.; Lee, S. P.; Liu, C.; Beak, P. J. Am. Chem. Soc. 1994, 116, 9755.
47. For cases in which the enantioselectivity reflects differences in ground state energies of diastereomeric organolithium complexes, see: Klute, W.; Kruger, M.; Hoffman, R. W. Chem. Ber. 1996, 129, 633.; Basu, A., Beak, P. J. Am. Chem. Soc. 1996, 188, 1575. For cases in which the enantioselectivity reflects the difference in transition state energies, ΔΔG‡, see: Hoffmann, R. W.; Rühl, T.; Harbach, J. Liebigs Ann. Chem. 1992, 725. Thayumanaman, S.; Lee, S. P.; Liu, C.; Beak, P. J. Am. Chem. Soc. 1994, 116, 9755.
48. We have found that i-PrLi does not form an observable complex with (-)-sparteine in THF solution and assume that applies to sec-BuLi as well. Long, S. A.; Beak, P. Unpublished result.
49. Suffert, J. J. Org. Chem. 1989, 54, 510.