(-)-Sparteine1

[90-39-1]  · C15H26N2  · (-)-Sparteine  · (MW 234.43) (sulfate pentahydrate)

[6160-12-9]  · C15H38N2O9S  · (-)-Sparteine  · (MW 422.62)

(reagent for chiral modification of organo-lithium, -magnesium, and -zinc reagents1,2)

Alternate Name: [(7S)-(7a,7aa,14a,14ab)]-dodecahydro-7,14-methano-2H,6H-dipyrido[1,2-a:1,2-e][1,5]diazocine.

Physical Data: bp 137-138 °C/1 mm Hg; d 1.02 g cm-3; [a]20D -17.5° (c = 2, EtOH). X-Ray structures of several complexes of metal salts,3 alkyllithium derivatives,4 and of allylpalladium5 and studies on the conformation in solution6 and a NMR study on the structure of the 2-propyllithium-ether-(-)-sparteine complex7 have been reported.

Solubility: 0.3 g/100 ml H2O at 20 °C; sol ether, hexane.

Form Supplied in: free base: colorless viscous fluid.

Handling, Storage, and Precautions: highly toxic in the digestive tract. Keep in refrigerator at 0 °C. Moderately hygroscopic; dehydration by drying an ethereal solution over Calcium Hydride. Is easily recovered by extraction of alkaline aqueous solutions. Use in a fume hood.

Chiral Modification of Achiral Organometallic Reagents.

The addition of n-Butyllithium or Ethylmagnesium Bromide to aldehydes or ketones in the presence of (-)- sparteine resulted in the formation of optically active secondary or tertiary alcohols with 20% ee or lower.8 Optically active acyl sulfoxides (<=15% ee) were obtained by acylation of p-Tolylsulfinylmethyllithium.9 The asymmetric Reformatsky reaction of ethyl bromoacetate with benzaldehyde proceeds with 95% ee,10 in an exceptional case (eq 1).11

Equilibration of Configurationally Labile Organolithium Reagents.

The equilibration of diastereomeric pairs of alkyllithium-(-)-sparteine complexes and trapping by achiral electrophiles gives enantioenriched products. Examples are a-(N,N-diisopropylcarbamoyloxy)benzyllithium in ether,12 not in THF,13 1-phenylethyllithium,8a and the dilithium salt of N-methyl-3-phenylpropanoic acid amide (eq 2).14

The deprotonation15 of (E)-2-butenyl N,N-diisopropylcarbamate leads to (1S,2E)-1-(N,N-diisopropylcarbamoyloxy)-2-butenyllithium-(-)-sparteine16 with &egt;90% de after crystallization, combined with a second-order asymmetric transformation (eq 3).4d It has been applied in the enantioselective synthesis of g-lactones,16 such as (+)-eldanolide (eq 3),17 dihydroavermectin B1b,18 and doubly branched sugar analogs.19

Generation of Enantioenriched, Configurationally Stable Organolithium Reagents.15,20

(1S,2E)-1-(N,N-Diisopropylcarbamoyloxy)-1-methyl-2-butenyllithium-(-)-sparteine is configurationally stable in solution and is obtained by kinetic resolution of the racemic 2-alkenyl carbamate by n-butyllithium-(-)-sparteine with &egt;80% de (eq 4).21 The enantioenriched allylstannane, obtained on g-stannylation, was used as chiral homoenolate reagent.21a The methoxycarbonylation (a, inversion) yields enantioenriched 3-alkenoates.21b

Alkyl carbamates, derived from 2,2,4,4-tetramethyl-1,3-oxazolidine (R-CH2-OCby), are deprotonated by s-Butyllithium-(-)-sparteine with differentiation between the enantiotopic protons (eq 5).22,20 The pro-S proton is removed with high stereoselectivity and reliability, and, subsequently, stereospecifically substituted by electrophiles with stereoretention to give enantiomerically enriched secondary alcohols (&egt;95% ee) after deprotection.22b

The ee values in the enantioselective deprotonation are independent of the size of the attached alkyl residue. The method tolerates several substituents, e.g. 2-23 or 3-dibenzylamino,24 3- or 4-(N,N-dialkylcarbamoyloxy),25 or 4-TBDMSO.25a Essentially enantiopure 2-hydroxy acids,22a b-amino alkanols,24 g-amino alkanols,23 cyclopropyl carbamates,25a and 2-hydroxy-4-butanolides25a were obtained. Extraordinary high (>70) kinetic H/D isotope effects were observed in the deprotonation of chiral 1-deuteroalkyl carbamates.26 Kinetic resolution of racemic alkyl carbamates was achieved.27

N-Boc-pyrrolidines are similarly deprotonated and furnish enantioenriched 2-substituted pyrrolidines (eq 6).28

Further Applications.

Chiral 1,1-diaryl-2-propynols are resolved by mutual crystallization with (-)-sparteine.29 Low ee values were achieved in Pd-mediated alkylations.30 Numerous attempts at enantioselective, alkyllithium-catalyzed polymerizations of alkenes in the presence of (-)-sparteine have been reported.31

Related Reagents.

(+)-Sparteine (pachycarpine32) is best prepared by resolution of (±)-sparteine, obtained from rac-lupanine33 or by total synthesis34 with (-)-10-camphorsulfonic acid.35


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2. Review: Tomioka, K. S 1990, 541.
3. For leading references see: Review: Kuroda, R.; Mason, S. F. JCS(D) 1977, 371.
4. (a) Engelhardt, L. M.; Leung, W.-P.; Raston, C. L.; Salem, G.; Twiss, P.; White, A. H. JCS(D) 1988, 2403. (b) Byrne, L. T.; Engelhardt, L. M.; Jacobsen, G. E.; Leung, W.-P.; Papasergio, R. I.; Raston, C. L.; Skelton, B. W.; Twiss, P.; White, A. H. JCS(D) 1989, 105. (c) Marsch, M.; Harms, K.; Zschage, O.; Hoppe, D.; Boche, G. AG 1991, 103, 338; AG(E) 1991, 30, 321. (d) Ledig, B.; Marsch, M.; Harms, K.; Boche, G. AG 1992, 104, 80; AG(E) 1992, 31, 79.
5. Togni, A.; Rihs, G.; Pregosin, P. S.; Ammann, C. HCA 1990, 73, 723.
6. (a) Bohlmann, F.; Schumann, D.; Arndt, C. TL 1965, 2705. (b) Wiewiorowski, M.; Edwards, O. E.; Bratek-Wiewiorowska, M. D. CJC 1967, 45, 1447.
7. Gallagher, D. J.; Kerrick, S. T.; Beak, P. JACS 1992, 114, 5872.
8. (a) Nozaki, H.; Aratani, T.; Noyori, R. T 1971, 27, 905. (b) Nozaki, H.; Aratani, T.; Toraya, T. TL 1968, 4097. (c) Aratani, T.; Gonda, T.; Nozaki, H. T 1970, 26, 5453.
9. Kunieda, N.; Kinoshita, M. PS 1981, 10, 383.
10. Guetté, M.; Capillon, J.; Guetté, J.-P. T 1973, 29, 3659.
11. Hansen, M. M.; Bartlett, P. A.; Heathcock, C. H. OM 1987, 6, 2069.
12. Hoppe, D.; Retzow, S. unpublished.
13. Zhang, P.; Gawley, R. E. JOC 1993, 58, 3223.
14. Beak, P.; Du, H. JACS 1993, 115, 2516.
15. Reviews: (a) Hoppe, D.; Krämer, T.; Schwark, J.-R.; Zschage, O. PAC 1990, 62, 1999. (b) Kunz, H.; Waldmann, H. Chemtracts Org. Chem. 1990, 3, 421.
16. (a) Zschage, O.; Hoppe, D. T 1992, 48, 5657. (b) Hoppe, D.; Zschage, O. AG 1989, 101, 67; AG(E) 1989, 28, 69.
17. Paulsen, H.; Hoppe, D. T 1992, 48, 5667.
18. Férézou, J. P.; Julia, M.; Khourzom, R.; Pancrazi, A.; Robert, P. SL 1991, 611.
19. Peschke, B.; Lüßmann, J.; Dyrbusch, M.; Hoppe, D. CB 1992, 125, 1421.
20. Review: Knochel, P. AG 1992, 104, 1486; AG(E) 1992, 31, 1459.
21. (a) Zschage, O.; Schwark, J.-R.; Krämer, T.; Hoppe, D. T 1992, 48, 8377. (b) Zschage, O.; Hoppe, D. T 1992, 48, 8389. (c) Zschage, O.; Schwark, J.-R.; Hoppe, D. AG 1990, 102, 336; AG(E) 1990, 29, 296.
22. (a) Hoppe, D.; Hintze, F.; Tebben, P. AG 1990, 102, 1457; AG(E) 1990, 29, 1422. (b) Hintze, F.; Hoppe, D. S 1992, 1216.
23. Schwerdtfeger, J.; Hoppe, D. AG 1992, 104, 1547; AG(E) 1992, 31, 1505.
24. Sommerfeld, P.; Hoppe, D. SL 1992, 764.
25. (a) Paetow, M.; Ahrens, H.; Hoppe, D. TL 1992, 33, 5323. (b) Ahrens, H.; Paetow, M.; Hoppe, D. TL 1992, 33, 5327.
26. Hoppe, D.; Paetow, M.; Hintze, F. AG 1993, 105, 430; AG(E) 1993, 32, 394.
27. Haller, J.; Hense, T.; Hoppe, D. SL 1993, 726.
28. Kerrick, S. T.; Beak, P. JACS 1991, 113, 9708.
29. (a) Toda, F.; Tanaka, K.; Ueda, H.; Oshima, T. CC 1983, 743. (b) Toda, F.; Tanaka, K.; Ueda, H.; Oshima, T. Isr. J. Chem. 1985, 25, 338.
30. Trost, B. M.; Dietsche, T. J. JACS 1973, 95, 8200.
31. For leading references see: Nakano, T.; Okamoto, Y.; Hatada, K. JACS 1992, 114, 1318.
32. Orechoff, A.; Rabinowitch, M.; Konowalowa, R. CB 1933, 66, 621.
33. Clemo, G. R.; Raper, R.; Short, W. S. JCS 1949, 663.
34. van Tamelen, E. E.; Foltz, R. L. JACS 1960, 82, 1960.
35. Ebner, T.; Eichelbaum, M.; Fischer, P.; Meese, C. O. AP 1989, 322, 399.

Dieter Hoppe

University of Münster, Germany



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