So far we have shown you conjugate additions mainly of α,β-unsaturated aldehydes and unsaturated α,β-ketones. You won’t be at all surprised to learn, however, that unsaturated acids, esters, amides, and nitriles—in fact all carboxylic acid derivatives—can also take part in conjugate addition reactions. Two examples, an amide and an ester, are shown on the right below. But notice how the selectivity of these reactions depends on the structure of the unsaturated compound: compare the way butyllithium adds to this α, β-unsaturated aldehyde and α, β-unsaturated amide. Both additions are irreversible, and BuLi attacks the reactive carbonyl group of the aldehyde, but prefers conjugate addition to the less reactive amide. Similarly, ammonia reacts with this acyl chloride to give an amide product that derives from direct addition to the carbonyl group, while with the ester it undergoes conjugate addition to give an amine.

In both of these cases, the site of nucleophilic attack is determined simply by reactivity: the more reactive the carbonyl group, the more direct addition to C=O will result. The most reactive carbonyl groups , are those that are not conjugated with O or N (as they are in esters and amides), and particularly reactive are acyl chlorides and aldehydes. In general, the proportion of direct addition to the carbonyl group follows the reactivity sequence in the margin. Sodium borohydride is a nucleophile that you have seen reducing simple aldehydes and ketones to alcohols, but it will also do conjugate addition reactions. Which of the alternatives actually takes place depends on the reactivity of the C=O group. NaBH₄ usually reacts with α, β-unsaturated aldehydes to give alcohols by direct addition to the carbonyl group.

Quite common with ketones, however, is the outcome below.

The borohydride has reduced not only the carbonyl group but the double bond as well. In fact, it’s the double bond that’s reduced first in a conjugate addition, followed by addition to the carbonyl group.

For esters and other less reactive carbonyl compounds conjugate addition is the only reaction that occurs because NaBH₄ doesn’t reduce esters or amides.

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

Nucleophilic epoxidation

Conjugate substitution reactions