1,2 vs. 1,4 addition to a carbonyl group

Whether 1,2 or 1,4-addition occurs depends on multiple variables but mostly it is determined by the nature of the nucleophile. During the addition of a nucleophile there is a competition between 1,2 and 1,4 addition products. If the nucleophile is a strong nucleophile, such as a Grignard reagent, both the 1,2 and 1,4 reactions are irreversible and therefore are under kinetic control. Since 1,2-additions to the carbonyl group are fast, we would expect to find a predominance of 1,2-products from these reactions.

If the nucleophile is a weak base, such as alcohols or amines, then the 1,2 addition is usually reversible. This means the competition between 1,2 and 1,4 addition is under thermodynamic control. In this case 1,4-addition dominates because the stable carbonyl group is retained.

Nucleophiles which add 1,4 to α,β unsaturated carbonyls

Water

Alcohols

Thiols

1^o Amines

2^o Amines

HBr

Cyanides

Gilman Reagents: These act as a source of R:^–

Example