Shi epoxidation

What is Shi epoxidation?

Shi et al. first reported the asymmetric epoxidation of olefins using chiral dioxirane generated in situ from Oxone (potassium peroxomonosulfate, KHSO: KHSO4 : K2SO4 = 2 : 1 : 1) in 1996. This reaction is commonly referred to as the Shi epoxidation and the Shi asymmetric epoxidation.

Shi epoxidation - general reaction scheme - Shi asymmetric epoxidation
Shi epoxidation

R1, R2, R3 = H, alkyl, aryl (see list of acronyms)

The ketone derivative of fructose-acetal is used as a reagent in this reaction. Acetonitrile has been found to be the best solvent for this reaction when used alone, leading to the highest substrate conversion and enantioselectivity. However, the best %e.e. for the epoxidation of trans-β-methylstryene can be obtained using a mixed solvent of CH3CN and dimethoxymethane (1:2). Diethyl ether, THF, CH2Cl2, and CH3CH2CN are poor solvents for this reaction.

The Shi epoxidation is particularly effective for the epoxidation of trisubstituted and trans-disubstituted olefins without other functional groups, and is a complementary method to the Sharpless epoxidation, especially for the epoxidation of allylic alcohols. This reaction can also tolerate a variety of functional groups, such as acetal, ester, chloro, and tributylsilyl ether.

Higher %e.e. of epoxidation can be achieved at lower reaction temperatures. However, prolonging the reaction time can decrease the %e.e. due to the decomposition of the chiral fructose derivative. Moreover, the Shi epoxidation competes with the Baeyer-Villiger oxidation from Oxone, but raising the pH (7–8) by adding K2CO3 to a pH of 10.5 can significantly enhance the catalyst’s efficiency.

Overall, the Shi epoxidation offers advantages such as mild reaction conditions, high %e.e. for unfunctionalized trans-olefins, and an easy workup process by hexane extraction of epoxides from Oxone.

References

  • Tu, Y.; Wang, Z.-X. and Shi, Y., J. Am. Chem. Soc., 1996, 118, 9806
  • Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R. and Shi, Y., J. Am. Chem. Soc., 1997, 119, 11224
Shares