11.12 : Base-Catalyzed Ring-Opening of Epoxides

Epoxides, due to their highly strained structures, readily undergo ring-opening reactions that are either acid-catalyzed or base-catalyzed.

Compared to acid-catalyzed reactions, base-catalyzed ring-openings require a strong nucleophile or a strong base, such as an alkoxide ion or a hydroxide ion.

For example, sodium ethoxide catalyzes the ring-opening reaction of 2,2-dimethyloxirane in ethanol solvent to give 1-ethoxy-2-methyl-2-propanol.

Mechanistically, the ethoxide ion executes a nucleophilic attack on the less substituted, primary carbon of epoxide in an S_N2 process and opens the epoxide ring to form an alkoxide ion.

The solvent then protonates the resulting alkoxide ion to give the corresponding product.

The epoxide ring can also be opened by a variety of other strong nucleophiles, such as sodium cyanide, sodium hydrosulfide, ammonia, Grignard reagent, and lithium aluminum hydride.

In contrast to epoxides, ethers do not readily undergo nucleophilic reactions. The infeasibility of these reactions can be understood by considering the potential energies of epoxides, ethers, and the corresponding alkoxide leaving groups.

Compared to linear ethers, epoxides are high-energy substrates due to their ring strain.

As a result, the activation energy required for the reaction is less for epoxides than for ethers.

Moreover, for epoxides, the products formed are lower in energy than the reactants. For ethers, however, the products are of higher energy.

 Hence, the reactions of epoxides with nucleophiles are thermodynamically favored.

Base-catalyzed ring-openings of epoxides show typical S_N2-like regioselectivity, in which the nucleophile attacks the less hindered carbon.

The stereoselectivity of these reactions is also like an S_N2 process. The nucleophilic attack is anti to the leaving group, causing an inversion of configuration at the chiral center.