11.9 : エポキシドの調製

Epoxides are prepared by the oxidation of alkenes using various oxidizing agents, and the reaction is known as epoxidation. 

Some of the most common oxidizing agents are peroxy acids, such as meta-chloroperoxybenzoic acid or mCPBA.

Peroxy acids are unique in having an electrophilic oxygen atom in the carboxylic group, which acts as the center for nucleophilic attacks.

Consider the oxidation of cis-2-butene using mCPBA to give cis-2,3-dimethyloxirane, with the mCPBA itself getting reduced to 3-chlorobenzoic acid.

The reaction proceeds via a cyclic transition state, wherein the alkene's π bond acts as a nucleophile and attacks the electrophilic oxygen of the peroxy acid to form the first carbon–oxygen bond of the epoxide.

Simultaneously, the oxygen–oxygen bond of the peroxy acid breaks, forming a new carbonyl bond.

Further, the π-electrons of the peroxy acid's original carbonyl bond abstract a proton from the OH bond to form a new OH bond. The oxygen then attacks the other carbon of the alkene, forming the second carbon–oxygen bond.

Overall, the electrophilic oxygen from the peroxy acid gets transferred to the double bond of the alkene, thus forming the epoxide ring. Since all the bond-breaking and bond-making occurs in a single step, the reaction is said to be concerted.

Stereospecifically, the epoxide ring installation on the alkene follows syn addition. Hence, a cis-alkene gives a cis-epoxide, and a trans-alkene gives a trans-epoxide.

Moreover, alkene's planar structure facilitates the nucleophilic attack and the formation of the epoxide ring from either face, yielding a meso compound for the cis- and a racemic mixture for the trans-epoxide. 

Halohydrins of alkenes, when treated with a base, can also form epoxides. The reaction is an intramolecular variation of the Williamson ether synthesis.

Consider the cyclization of 3-chloro-2-butanol, a halohydrin derived from cis-2-butene, to give cis-2,3-dimethyloxirane.

The reaction proceeds via the deprotonation of halohydrin's hydroxyl group by the base to form the alkoxide ion, a nucleophile.

Typical of an S_N2 reaction, the nucleophile attacks from the backside and displaces the chloride ion on the adjacent carbon forming the oxirane ring. Consequently, the epoxide formed retains the alkene stereospecificity.