Although epoxides, like bromonium ions, contain strained three-membered rings, they require either acid catalysis or a powerful nucleophile to react well. Compare these two reactions of a 1,1,2-trisubstituted epoxide. They are nucleophilic substitutions related to those , but in that chapter we carefully avoided discussing epoxides of the unsymmetrical variety. In this example, the regiochemistry reverses with the reaction conditions. Why?

We’ll start with the acid-catalysed reaction because it is more similar to the examples we have just been discussing—opening happens at the more substituted end. Protonation by acid produces a positively charged intermediate that bears a passing resemblance to the corres ponding bromonium ion. The two alkyl groups make possible a build-up of charge on the carbon at the tertiary end of the protonated epoxide, and methanol attacks here, just as it does in the bromonium ion. You could think of the protonated leaving group ‘pulling’ the otherwise unreactive methanol in towards the reactive centre.

In base there can be no protonation of the epoxide and no build-up of positive charge. Without protonation, the epoxide oxygen is a poor leaving group, and leaves only if ‘pushed’ by a strong nucleophile: the reaction becomes pure SN2. Steric hindrance becomes the con trolling factor and methoxide attacks only the primary end of the epoxide.

This example makes the matter look deceptively clear cut. But with epoxides, regioselectivity is not as simple as this because, even with acid catalysts, SN2 substitution at a primary centre is fast. For example, Br − in acid attacks the epoxide below mainly at the less substituted end, and only 24% of the product is produced by the ‘cation-stabilized’ pathway. It is very difficult to override the preference of epoxides unsubstituted at one end to react at that end.

For most substitution reactions of epoxides, then, regioselectivity is much higher if you give in to the epoxide’s desire to open at the less substituted end and enhance it with a strong nucleophile under basic conditions.

مواضيع ذات صلة

Enolization is catalysed by acids and bases

Evidence for the equilibration of carbonyl compounds with enols

Tautomerism: formation of enols by proton transfer

Hydration of alkynes

Breaking a double bond completely: periodate cleavage and ozonolysis

Adding two hydroxyl groups: dihydroxylation

Electrophilic addition to alkenes can produce stereoisomers

Hydration of alkynes

Breaking a double bond completely: periodate cleavage and ozonolysis

Adding two hydroxyl groups: dihydroxylation

Electrophilic addition to alkenes can produce stereoisomers

Electrophilic additions to alkenes can be stereospecific