15.36 : Conjugate Addition (1,4-Addition) vs Direct Addition (1,2-Addition)

α,β-Unsaturated carbonyl compounds with two electrophilic sites, the carbonyl carbon, and the β carbon, are susceptible to nucleophilic attack via two modes: conjugate or 1,4-addition and direct or 1,2-addition.

Conjugate addition results in a thermodynamically stable product. The reaction retains the stronger C=O bond at the expense of the weaker C=C π bond. The process is slow as the β carbon is less electrophilic than the carbonyl carbon.

Direct addition products are formed faster owing to the greater electrophilicity of the carbonyl carbon. The process is said to be under kinetic control and yields a less stable product due to the loss of the stronger C=O π bond.

One of the factors that decide the predominant product is the nature of the nucleophile. Generally, stronger nucleophiles such as lithium aluminum hydride, Grignard reagents, and organolithium reagents favor 1,2-addition. However, Grignard reagents can also yield a mixture of products. Thus, organolithium reagents are used to obtain the primarily direct addition product, while weaker nucleophiles such as lithium diorganocuprates, primary amines, and thiolates yield the conjugate addition product.