(+)-Sparteine Surrogate

Dr. Daniel Weibel

Until recently, sparteine, a widely used ligand in asymmetric synthesis1-5 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 1 turned out to be the most versatile and widely applicable one.6

 N-methyl derivative

Figure 1.

A simple, three-step synthesis starting from Laburnum anagyroides cytisus seeds, subsequent N-protection, diastereoselective pyridone hydrogenation, and lithium aluminum hydride reduction synthesized (Scheme 1).7

three-step synthesis

Scheme 1.(712264)

In a diverse range of examples 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.6,7

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).

We are 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.

Materials
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References

1.
Hoppe D, Hense T. 1997. Enantioselective Synthesis with Lithium/(?)-Sparteine Carbanion Pairs. Angew. Chem. Int. Ed. Engl.. 36(21):2282-2316. http://dx.doi.org/10.1002/anie.199722821
2.
Beak P, Basu A, Gallagher DJ, Park YS, Thayumanavan S. 1996. Regioselective, Diastereoselective, and Enantioselective Lithiation?Substitution Sequences:  Reaction Pathways and Synthetic Applications. Acc. Chem. Res.. 29(11):552-560. http://dx.doi.org/10.1021/ar950142b
3.
(c) Clayden, J. Organolithiums: Selectivity for Synthesis, Pergamon, New York, 2002.
4.
(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.
5.
Hoppe D, Kaiser B, Stratmann O, Fröhlich R. 1997. A Highly Enantiomerically Enriched?-Thiobenzyl Derivative with Unusual Configurational Stability. Angew. Chem. Int. Ed. Engl.. 36(24):2784-2786. http://dx.doi.org/10.1002/anie.199727841
6.
O'Brien P. Basic instinct: design, synthesis and evaluation of (+)-sparteine surrogates for asymmetric synthesis. Chem. Commun..(6):655-667. http://dx.doi.org/10.1039/b711420f
7.
2006. SYNTHESIS OF (+)-(1R,2S,9S)-11-METHYL-7,11-DIAZATRICYCLO[7.3.1.02,7]TRIDECANE, A (+)-SPARTEINE SURROGATE. Org. Synth.. 83141. http://dx.doi.org/10.15227/orgsyn.083.0141