23.11: Conjugate Carbonyl Additions - The Michael Reaction
- Page ID
- 448811
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)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)?