The conjugate substitutions we have just been discussing rely on a starting material contain ing a leaving group. In this section we are going to look at what happens if the leaving group is not attached to the unsaturated carbonyl compound, but instead is attached to the nucleophile. We shall look at this class of compounds—nucleophiles with leaving groups attached , but for the moment the most important will be hydroperoxide, the anion of hydrogen peroxide. Hydroperoxide is a good nucleophile because of the alpha effect: interaction of the two lone pairs on adjacent oxygen atoms raises the HOMO of the anion and makes it a better and softer nucleophile than hydroxide. Hydroperoxide is also less basic than hydroxide because of the inductive electron-withdrawing effect of the second oxygen atom. Basicity and nucleophilicity usually go hand in hand—not here though. This means that the hydroperoxide anion can be formed by treating hydrogen peroxide with aqueous sodium hydroxide.

This is what happens when this mixture is added to an enone. First, there is the conjugate addition.

But the product is not stable because hydroxide can be lost from the oxygen atom that was the nucleophile. Hydroxide is fine as a leaving group here—after all, hydroxide is lost from enolates in E1cB eliminations, and here the bond breaking is a weak O–O bond. The product is an epoxide.

The electrophilic epoxidizing agents such as m-CPBA , work reliably only with nucleophilic alkenes, and for α,β-unsaturated carbonyl compounds and other electron-deficient alkenes, hydroperoxide—a nucleophilic epoxidizing agent—is often used instead. There is another significant difference between hydrogen peroxide and m-CPBA, highlighted by the pair of reactions below.

m-CPBA epoxidation is stereospecific because the reaction happens in one step. But nucleophilic epoxidation with hydroperoxide is a two-step reaction: there is free rotation about the bond market in the anionic intermediate, and the more stable, trans-epoxide results, what ever the geometry of the starting alkene.

مواضيع ذات صلة

How to reduce carboxylic acids to alcohols

How to reduce amides to amines

The benzyne mechanism

Other nucleophiles

The SN1 mechanism for nucleophilic aromatic substitution: diazonium compounds

The activating anion-stabilizing substituent

The leaving group and the mechanism

The intermediate in the addition–elimination mechanism

The addition–elimination mechanism

Nucleophilic aromatic substitution

Conjugate substitution reactions

Unsaturated nitriles and nitro compounds