Epoxidation with dioxiranes

Epoxidation with dioxiranes refers to the synthesis of epoxides from alkenes using three-membered cyclic peroxides, also known as dioxiranes.

Dioxiranes are three-membered cyclic peroxides containing a weak oxygen-oxygen bond. Although they are able to effect oxidations of heteroatom functionality and even carbon-hydrogen bonds, they are most widely used as epoxidizing agents of alkenes. Dioxiranes are electrophilic oxidants that react more quickly with electron-rich than electron-poor double bonds; however, both classes of substrates can be epoxidized within a reasonable time frame. Dioxiranes may be prepared and isolated or generated in situ from ketones and potassium peroxymonosulfate (Oxone). In situ preparations may be catalytic in ketone, and if the ketone is chiral, enantioselective epoxidation takes place. The functional group compatibility of dioxiranes is limited somewhat, as side oxidations of amines and sulfides are rapid. Nonetheless, protocols for dioxirane oxidations are entirely metal free. The most common dioxiranes employed for synthesis are dimethyl dioxirane (DMD) and methyl(trifluoromethyl)dioxirane (TFD).

The mechanism of epoxidation with dioxiranes most likely involves concerted oxygen transfer through a spiro transition state. As oxygen transfer occurs, the plane of the oxirane is perpendicular to and bisects the plane of the alkene pi system. The configuration of the alkene is maintained in the product, ruling out long-lived radical intermediates. In addition, the spiro transition state has been used to explain the sense of selectivity in enantioselective epoxidations with chiral ketones.

Diastereoselective epoxidation may be achieved through the use of alkene starting materials with diastereotopic faces. When racemic 3-isopropylcyclohexene was subjected to DMD oxidation, the trans epoxide, which resulted from attack on the less hindered face of the double bond, was the major product.

Enantioselective epoxidation using dioxiranes exploits one of two strategies: (1) oxidation by DMD of a chiral metal catalyst followed by epoxidation, or (2) epoxidation by chiral dioxiranes, which are generated in situ from a catalytic amount of ketone and a stoichiometric amount of a terminal oxidant). Mn-salen complexes have been used with success to accomplish the first strategy.

Many of the best ketones for the second strategy are derived from carbohydrates. For instance, Shi's catalyst 1 is derived from fructose, and epoxidizes both di- and trisubstituted alkenes with high enantioselectivity.

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