(+)-Sparteine Surrogate

By: Dr. Daniel Weibel, Chemfiles Volume 10 Article 1

Until recently, sparteine, a widely used ligand in asymmetric synthesis1 was only commercially available in one enantiomeric form. O'Brien and his coworkers have designed several (+)-sparteine surrogates, which possess most of the threedimensional architecture of (+)-sparteine. However the N-methyl derivative (690279) shown in Figure 2 turned out to be the most versatile and widely applicable one.2

Figure 2

Figure 2


A simple, three-step synthesis starting from Laburnum anagyroides cytisus seeds, subsequent N-protection, diastereoselective pyridone hydrogenation, and lithium aluminum hydride reduction synthesized (Scheme 6).3

Scheme 6

Scheme 6: (712264)


In a diverse range of examples collected in Table 1, it was shown that all of the products show opposite enantioselectivity and a relatively equal high degree of enantioselection when using the (+)-sparteine surrogate (690279) to those when using (-)-sparteine.2,3

Lithiations and subsequent rearrangement or electrophilic trapping are particularly successful (Entries 1–4). The use of (+)-sparteine surrogate 690279 is not limited to organolithium-mediated processed reactions, magnesium, copper, and palladium are also successful. Exceptional examples include sparteine-mediated Grignard reactions in the desymmetrization of meso-anhydrides (Entry 5), and the copper(II)-mediated dynamic thermodynamic resolution of racemic BINOL (Entry 6).

Sigma-Aldrich is pleased to now offer (+)-sparteine surrogate (690279) thus allowing access to a range of products of opposite absolute configuration to those obtained by using (-)-sparteine.

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Materials

     

References

  1. (a) Hoppe, D.; Hense, T . Angew. Chem., Int. Ed. Engl., 1997, 36, 2282 (b) Beak, P.; Basu, A.; Gallagher, D. J.; Park, Y. S. ;Thayumanavan, S. Acc. Chem. Res., 1996, 29, 552 (c) Clayden, J. Organolithiums: Selectivity for Synthesis, Pergamon, New York, 2002 (d) Gawley, R. E.; Coldham, I. The Chemistry of Organolithium Compounds, in The Chemistry of Functional Groups, ed. Z. Rappoport and I. Marek, Wiley, Chichester, 2004, p. 997 (e) Hoppe D.; Christoph, G. ibid., p. 1077.
  2. (a) O'Brien, P. Chem. Commun. 2008, 655 (b) Dearden, M. J.; McGrath, M. J.; O'Brien, P. J. Org. Chem. 2004, 69, 5789.
  3. Dixon, A. J.; McGrath, M. J.; O'Brien, P. Org. Synth. 2006, 83, 141.

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