Michael Addition

The Michael addition is a carbon-carbon bond-forming reaction extensively used in organic chemistry. It consists of the nucleophilic addition of an activated nucleophile (Michael donor) to an α,β-unsaturated carbonyl compound (Michael acceptor). It belongs to the class of conjugate additions or 1,4-addition reaction.

General features:

The main drawback of the Michael reaction is that other processes may compete with the desired 1,4-addition. For example 1,2-addition reactions or self-condensation of the carbon nucleophile. These side reactions can be suppressed or minimized by the use of certain additives or solvents.

Michael Addition

Michael Reaction

Reaction Mechanism

Michael Reaction
Michael Reaction

1. Deprotonation of the Michael donor by a base. 2. Conjugate addition reaction between the nucleophile and the Michael acceptor. 3. Proton abstraction from the protonated base leads to the final product.

Example

Angew. Chem. Int. Ed. 2020, 59, 22039.

Michael Reaction

Experimental Procedure

Michael Reaction

The Michael acceptor, acrylonitrile (1.2 eq), was added dropwise to a mixture of the Michael donor (101.9 mmol, 1.0 eq) and anhydrous K2CO3 (2.0 eq) in acetone (500 mL) at rt. The reaction mixture was stirred for 40 h at the same temperature, after completion of the reaction (TLC), filtered through a pad of celite, and concentrated in vacuo to remove the solvent. The resulting crude residue was diluted with ethyl acetate and washed with water and brine. The combined organic layers were dried over Na2SO4, and concentrated in vacuo. The crude compound was purified by silica-gel column chromatography to deliver the desired product (72% yield).

Additional Examples

J. Am. Chem. Soc. 2019, 141, 19589.

Michael Reaction

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