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 \(\PageIndex{1}\). 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 \(\PageIndex{1}\)). 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 acceptors.1 Michael donors Michael donors.1 CH2=CH-CH=O Propenal NaN β-Diketone NaN 3-Buten-2-one NaN β-Keto ester NaN Ethyl propenoate NaN Diethyl malonate NaN Propenamide NaN β-Keto nitrile NaN Propenenitrile NaN Nitro compound NaN Nitroethylene NaN NaN Worked Example \(\PageIndex{1}\): 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 Exercise \(\PageIndex{1}\) What product would you obtain from a base-catalyzed Michael reaction of 2,4-pentanedione with each of the following α, β -unsaturated acceptors? 2-Cyclohexenone Propenenitrile Ethyl 2-butenoate Answer Exercise \(\PageIndex{2}\) What product would you obtain from a base-catalyzed Michael reaction of 3-buten-2-one with each of the following nucleophilic donors? Answer Exercise \(\PageIndex{3}\) How would you prepare the following compound using a Michael reaction (gray = H, black = C, red = O, blue = N)? Answer CH 3 CH 2 COCH═CH 2 + CH 3 CH 2 NO 2