15.36 : 共役付加 (1,4-付加) vs 直接付加 (1,2-付加)

α,β-unsaturated carbonyl compounds undergo nucleophilic attack via two possible modes—conjugate or 1,4-addition and direct or 1,2-addition.

Conjugate-addition products are thermodynamically controlled. They form slowly as the β carbon is less electrophilic, and they are more stable since the stronger carbonyl bond is retained while the weaker C=C π bond is lost.

Direct-addition products are kinetically controlled. They form faster as the carbonyl carbon is more electrophilic, and they are less stable since the stronger carbonyl bond is lost.

A significant factor determining the type of nucleophilic addition is the nature of the nucleophiles.

Strong nucleophiles like LAH, Grignard reagents, and organolithium reagents favor simple 1,2-addition to give corresponding products.

Grignard reagent, in some cases, gives a mixture of products. So, to exclusively get the 1,2-addition product, organolithium reagents are preferred.

Weak nucleophiles like lithium diorganocuprates and primary amines add to the β carbon, predominantly giving 1,4-addition products.