This week’s choice is a review from the Jørgensen group at the Aarhus University in Denmark dealing with the asymmetric organocatalytic epoxidation reaction. Now as we all know epoxides play a powerful role in organic chemistry as building blocks for more complex systems they also exist as a structural unit in many natural products. Chiral epoxides are, of course, more interesting and a number of methods exist to prepare them, for example the Sharpless asymmetric epoxidation of allylic alcohols using titanium tartrates as catalysts. Jacobsen and Katsuki have also been very active in this area. This review provides an overview of the various organocatalytic systems available for asymmetric epoxidation.

The Juliá-Colonná epoxidation employs poly-L-alanine or poly-L-leucine to catalyse the epoxidation of electron deficient alkenes. This has been reviewed. One example of such a catalyst for the epoxidation of α,β-unsaturated ketones is:

The conditions are 670 wt% of the “catalyst”, in urea/hydrogen peroxide, DBU in THF. This produces a chiral epoxide in anywhere between 78-85% yield and 93% ee. Now if this is catalytic then I need to re-read my books. It is re-cyclable but imagine 1 kg of substrate requires 670 kg catalyst. (Thanks to one of our readers for spotting an error, for 670 kg please read 6.7 kg).

Slightly better activity is achieved in the epoxidation of substituted styrenes using the following peptidic trifluoromethyl ketone :

Here the conditions are a bit mote catalytic, 5 mol% of the above with hydrogen peroxide, potassium carbonate, di-sodium EDTA, acetonitrile, tert-amyl alcohol/water gives 75-89% yield and 39-82% ee. The reaction is presumed to proceed vis a dioxirane intermediate.

Moving through this review one comes across carbohydrate based ketones as catalysts, for example-

Pioneered by Shi etal these fructose derivatives are very effective for dioxirane asymmetric epoxidations. The one above balances steric and electronic effects, that is the chiral units are placed adjacent to the carbonyl group and the alkene approach is restricted to one face of catalyst. A problem with these catalysts is the competing Bayer-Villiger oxidation thus requiring higher pH and catalyst loads. This catalyst has been successfully utilised in the synthesis of a couple of natural products.

Asymmetric phase transfer catalysis is also frequently employed especially those based on the cinchona alkaloids. In combination with NaOCl they are particularly effective  for the epoxidation of α,β-unsaturated ketones. Chiral crown ethers have also been used.

This review will prove to be useful to those confronted with this synthetic problem. It highlights many examples that have been reduced to practice and discusses the probable mechanistic rational for the results observed. A welcome addition to the literature collection.