Michael reaction or nucleophilic attack at the alpha carbon of an alpha-beta-unsaturated ketone?

Question

What conditions promote a nucleophile to undergo the Michael reaction over the nucleophilic attack at the alpha carbon of the carbonyl group in an alpha-beta-unsaturated ketone? I'm looking for an answer that considers organic and inorganic nucleophiles (like organocuprates/organolithium compounds).

Answer 1

An $\alpha,\beta$-unsaturated ketone is electrodeficient at the $\beta$ position. This can be seen if you draw the resonance structures of such a molecule.

The $\beta$ carbon is thus a good site for nucleophilic attack. But, as you know, carbonyls are also prone to nucleophilic attack. To discriminate between the two, you need to look at how the reaction is controlled, either thermodynamically or kinetically.

In a kinetically controlled reaction, the product that is formed fastest predominates. In a thermodynamically controlled reaction, the predominant product is the energetically favored one.

A Michael addition is a 1-4 addition, where a nucleophile attacks the $\beta$ carbon, and produces the thermodynamically favored product. On the other hand, a 1-2 reaction (on the carbonyl) gives the kinetic product, and is obtained at low temperatures.

Why is the 1-4 product thermodynamically more stable? Because the resulting product benefits from keto-enol tautomerism, which results in lowering the energy of the system. Usually, the more resonance forms a compound has, the more its electrons are delocalized, the more stable it is.

Draw the resonance forms of the 1-4 and 1-2 products, and see.

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You asked for specific affinities of different organometallics in 1-4/1-2 additions. My knowledge is that organocuprates ($\mathrm{R-CuLi}$) will perform Michael additions, and that organolithians seem to prefer 1-2 addition. Also, according to this source, Grignard reagents do not seem to have a preference.

My take on this is that the cuprate is less reactive, and therefore can form the thermodynamic product, whereas the lithium reagent is so destabilized that it reacts right away.

Answer 2

It must first be understood that Michael Addition is a special type of conjugate (1,4) addition where the nucleophilic species is an enolate. This will undergo 1,4 addition to the A-B unsaturated carbonyl.

Organocuprates add in a 1,4 fashion. The mechanism behind this is not fully understood, but it is known that radical intermediates are involved. Organolithium agents add in a 1,2 fashion. The reason for this is that the organolithium is very close to a carbanion and it will attack the most positive species in the molecule. In this case, the carbonyl carbon is the most electrophilic and so the organolithium will attack there. For reference, organomagnesium compounds are fickle and can attack either 1,2 or 1,4.

The alpha carbon is the carbon adjacent to the carbonyl carbon. The alpha carbon is actually quite nucleophilic (which is aldol condensation, alpha-alkylation, and alpha halogenation can occur). So, a nucleophile will attack either the partially positive berta carbon or the carbonyl carbon.