Schmidt glycosylation

What is Schmidt glycosylation?

The Schmidt glycosylation is a Lewis acid-catalyzed glycosylation reaction that uses glycosyl trichloroacetimidate as the donor. The reaction was first reported in 1976 by Sinaÿ and extensively explored by Schmidt et al. since 1980. It is sometimes referred to as the Schmidt glycosidation, Schmidt coupling, or Schmidt trichloroacetimidate method.

Schmidt glycosylation - general reaction scheme
Schmidt glycosylation
  • P = protecting group
  • R = alkyl, carbohydrate, etc.
  • Lewis acid = TMSOTf, BF3 · Et2O, etc. (see list of acronyms)

This reaction is widely used in carbohydrate transformations due to its mildly acidic coupling conditions and the opportunities to alter α/β selectivity via different glycosyl trichloroacetimidate donors and/or coupling reagents. Glycosyl trichloroacetimidate can be prepared by treating a carbohydrate precursor with trichloroacetonitrile in the presence of a base, such as DBU, K2CO3, Cs2CO3, or NaH. The use of different bases can influence the α/β selectivity. Mild acids compatible with this glycosylation include TMSOTf, BF3·Et2O, TBDMSOTf, TBSOTf, and perchloric acid. The selectivity of the reaction can be influenced by the choice of the glycosyl donor and the coupling reagents. For instance, TMSOTf, TBDMSOTf, and AgOTf often lead to the formation of a β-glycosidic linkage, whereas in the presence of BF3·Et2O promoter, α-glycoside is favored. The general 1,2-trans selectivity of glycosylation also applies to this reaction.

References

  • Pougny, J.-R. and Sinaÿ, P., Tetrahedron Lett., 1976, 4073
  • Schmidt, R. R. and Michel, J., Angew. Chem. Int. Ed. Engl., 1980, 19, 731
  • Schmidt, R. R., Angew. Chem. Int. Ed. Engl., 1986, 25, 212
  • Schmidt, R. R. and Kinzy, W., Adv. Carbohydr. Chem. Biochem., 1994, 50, 21
  • Schmidt, R. R. and Jung, K.-H., Oligosaccharide Synthesis with Trichloroacetimidates in Preparative Carbohydrate Chemistry, ed. Hanessian, S, Dekker, New York, 1997, pp. 283–312.
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