23.11: Conjugate Carbonyl Additions - The Michael Reaction
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We saw in Section 19.13 that certain nucleophiles, such as amines, react with α,β-unsaturated aldehydes and ketones to give a conjugate addition product, rather than a direct addition product.
Exactly the same kind of conjugate addition can occur when a nucleophilic enolate ion reacts with an α,β-unsaturated carbonyl compound—a process known as the Michael reaction after Arthur Michael at Tufts College and Harvard University.
The best Michael reactions are those that take place when a particularly stable enolate ion, such as that derived from a β-keto ester or other 1,3-dicarbonyl compound, adds to an unhindered α,β-unsaturated ketone. For example, ethyl acetoacetate reacts with 3-buten-2-one in the presence of sodium ethoxide to yield the conjugate addition product.
Michael reactions take place by addition of a nucleophilic enolate ion donor to the β carbon of an α,β-unsaturated carbonyl acceptor, according to the mechanism shown in Figure 23.7.
Figure 23.7 MECHANISM Mechanism of the Michael reaction between a β-keto ester and an α,β-unsaturated ketone. The reaction is a conjugate addition of an enolate ion to the unsaturated carbonyl compound.
The Michael reaction occurs with a variety of α,β-unsaturated carbonyl compounds, not just conjugated ketones. Unsaturated aldehydes, esters, thioesters, nitriles, amides, and nitro compounds can all act as the electrophilic acceptor component in Michael reactions (Table 23.1). Similarly, a variety of different donors can be used, including β-diketones, β-keto esters, malonic esters, β-keto nitriles, and nitro compounds.
| Michael acceptors | Michael donors | ||
|---|---|---|---|
| Propenal | β-Diketone | ||
| 3-Buten-2-one | β-Keto ester | ||
| Ethyl propenoate | Diethyl malonate | ||
| Propenamide | β-Keto nitrile | ||
| Propenenitrile | Nitro compound | ||
| Nitroethylene | |||
Worked Example 23.5
Using the Michael Reaction
How might you obtain the following compound using a Michael reaction?
Strategy
A Michael reaction involves the conjugate addition of a stable enolate ion donor to an α,β-unsaturated carbonyl acceptor, yielding a 1,5-dicarbonyl product. Usually, the stable enolate ion is derived from a β-diketone, β-keto ester, malonic ester, or similar compound. The C–C bond formed in the conjugate addition step is the one between the α carbon of the acidic donor and the β carbon of the unsaturated acceptor.
Solution
α,β-unsaturated acceptors? (a)
2-Cyclohexenone
(b)
Problem 23-18
How would you prepare the following compound using a Michael reaction (gray = H, black = C, red = O, blue = N)?