Weitz-Scheffer epoxidation

What is Weitz-Scheffer epoxidation?

The Weitz-Scheffer epoxidation is a commonly used method for epoxidizing electron-deficient olefins with hydrogen peroxide H2O2 in a strong alkaline solution. The Weitz-Scheffer epoxidation, was widely used since Wynberg work in 1976 which employs cinchona alkaloids as an asymmetric induction catalyst.

Different oxygen sources, such as tert-butyl hydroperoxide, cumene hydroperoxide, hypochlorite, and molecular oxygen, have been used in this method.

Weitz-Scheffer epoxidation - general reaction scheme
Weitz-Scheffer epoxidation
  • R1 = alkyl, aryl
  • R2 = H, alkyl, aryl

The most important modification of the asymmetric Weitz-Scheffer epoxidation is the use of optically active secondary hydroperoxide as the oxidation reagent, in the presence of either KOH or an organic base like DBU (see list of acronyms). Enantioselectivity is achieved by carrying out the reaction in CH3CN at -40 ºC. The steric interaction among the aggregated species of α,β-enone substrate, hydroperoxide, and KOH leads to the (αS,βR)-epoxide in preference due to the small steric hindrance between the β-substituent of the enone and the substituent at the chiral center of (-)-(S)-1-phenylethyl hydroperoxide during the (Si)-face attack. Steric repulsion during epoxidation is enhanced with the increasing size of β-substituent in α,β-enone. However, electron-donating substituents on the chalcone do not significantly affect enantioselectivity.

Weitz-Scheffer epoxidation - general reaction scheme
Weitz-Scheffer epoxidation

Potassium cation has a profound effect on the enantioselectivity due to the formation of a coordination complex. The enantioselectivity is dramatically diminished when potassium cation is removed from the reaction system, and the potassium chelating agent (i.e., 18-crown-6) is added. If the organic base DBU is used instead of KOH in this epoxidation, the enantioselectivity is decreased. Interestingly, in the presence of DBU, the oxygen-transfer process is different, resulting in a prevailing (Re)-face attack to give (αR,βS)-epoxide.

References

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