Conjugate (1,4) or Michael Addition

The non-conjugate addition takes place on adjacent atoms (1,2) of the conjugated system.

There are two possibilities: attack on the C=C or on the C=O.

In either case, the nucleophilic part of the reagent (Y) ends up bonded to one of the electron-deficient centers (blue).

The conjugate addition takes place at both ends (1,4) of the conjugated system. There is only one possibility: the nucleophilic part of the reagent (Nuc) attaches to the electron-deficient end of the system. One double bond remains, but it shifts to the central position. When the reagent is Nuc–H, or when a proton is added in a second hydrolysis step, an enol is formed, whose equilibrium with the corresponding aldehyde or ketone is shifted toward the latter.

In the addition of cyanide, the nucleophilic part is CN and the electrophilic part is the potassium ion. An enolate is formed, which is immediately neutralized by acetic acid to give an enol in tautomeric equilibrium with the ketone. The final result of the example is the 1,4-addition of cyanide to 1,3-diphenylpropenone.

Grignard reagents are usually non-selective.

The example shows that they are like a bull in a china shop: ethylmagnesium bromide attacks both in a conjugate fashion and directly at the carbonyl group.

An inconvenient mixture is obtained.

Organolithium reagents are indeed selective, but they treat the carbonyl group as if it were isolated.

They ignore the C=C double bond.

In the example, the phenyl group is the nucleophilic part and the metal is the electrophile.

Organolithium compounds are easily converted into organocuprates by reaction with copper(I) iodide.

Organocuprates are organometallic reagents with a more covalent C–metal bond and are therefore less reactive than organolithium compounds.

The carbon bonded to the Cu atom is the nucleophilic part, which attacks 2-cyclohexenone at its electrophilic part, the C=C double bond.

A new C–C bond and an enolate are formed; reaction of the enolate with water gives the enol, which immediately equilibrates with the ketone, predominant in the keto-enol equilibrium.

LAH is very reactive and always attacks the carbonyl group, as if it were isolated.

It ignores the C=C double bond.

Sodium borohydride is less reactive than LAH.

Paradoxically, it is not regioselective.

Its use is not advisable with α,β-unsaturated aldehydes or ketones because it gives mixtures of reduction products that are difficult to separate.

Catalytic hydrogenation treats α,β-unsaturated aldehydes or ketones as if the C=C and C=O double bonds were isolated.

Since a C=C double bond reacts more easily than a C=O in this reaction, it is reduced first, as shown in the example.