Ethers from Alkenes: Alcohol Addition and Alkoxymercuration-Demercuration

Acid-catalyzed alcohol addition to alkenes involves treating the alkene with excess alcohol and an acid catalyst. The acid protonates the alkene's π bond, forming a carbocation intermediate. The alcohol's oxygen nucleophilically attacks this carbocation, creating an oxonium ion. Proton transfer completes the reaction, yielding the ether product.

Mercuric acetate acts as an electrophile in the first step of alkoxymercuration-demercuration. It attacks the alkene's π bond, forming a bridged mercurinium ion intermediate. This intermediate is then opened by nucleophilic attack from the alcohol, positioning the alkoxy group according to Markovnikov's regioselectivity before sodium borohydride reduces the organomercury intermediate to form the ether.

Alkoxymercuration-demercuration follows Markovnikov's regioselectivity because the alcohol nucleophile attacks the more-substituted carbon of the mercurinium ion intermediate. This regioselectivity ensures the alkoxy group attaches to the more-substituted carbon while hydrogen adds to the less-substituted carbon, consistent with Markovnikov's rule for alkene additions.

Acid-catalyzed addition uses an acid catalyst and forms a carbocation intermediate directly on the alkene. Alkoxymercuration-demercuration uses mercuric acetate to form a bridged mercurinium ion intermediate instead. Both methods follow Markovnikov's regioselectivity, but alkoxymercuration-demercuration is anti-addition and generally more selective, avoiding carbocation rearrangement.

Ditertiary ethers cannot be prepared by alkoxymercuration-demercuration due to steric hindrance. When both carbons of the alkene are highly substituted, the bulky alkoxy group and the bridged mercurinium ion intermediate create excessive steric clashes, preventing the nucleophilic attack necessary to open the intermediate and form the ether product.

After the alcohol attacks the more-substituted carbon of the mercurinium ion, the ring opens and the intermediate is deprotonated to form an organomercury intermediate. Sodium borohydride then acts as a reducing agent, substituting the mercury acetate group with a hydride to produce the final ether product.

Ethers from alkenes offer alternatives to ethers from alcohols through alcohol dehydration and Williamson ether synthesis. Acid-catalyzed addition and alkoxymercuration-demercuration both convert alkenes directly to ethers with high regioselectivity. These methods are particularly useful when traditional alcohol-based syntheses are impractical or when specific regiochemical outcomes are required.