Michael Addition Reaction or 1,4-Conjugate Addition

Michael reaction is the nucleophilic addition of carbanion to the 𝛂,𝜷-unsaturated carbonyl compounds. This is a type of conjugate addition reaction and is also known as a 1,4 addition reaction. This reaction was discovered by Arthur Michael in 1887. In this reaction, enolate ion acts as Michael donor whereas, unsaturated carbonyl compounds act as Michael acceptors.

general example of michael addition reaction or 1,4-conjugate addition

Michael reaction takes place in the presence of a base. Base act as a catalyst. It consists of two reactants/substrates. One of the reactants is enolate anion also called carbanion. It acts as Michael’s donor. It is the nucleophile. Whereas the second reactant is 𝛂,𝜷-unsaturated carbonyl compound having an electron-withdrawing group.

Micheal reaction involves the nucleophilic addition and 𝛂-substitution reaction. Micheal donor undergoes 𝛂-substitution whereas Michael acceptor undergoes nucleophilic addition reaction. Carbonion is a nucleophile which added to the 𝛂-carbon of Michael acceptor. It is electrophilic in nature because of electron-withdrawing groups in conjugation. Michael’s reaction takes place easily in the presence of stable enolates and unhindered 𝛂,𝜷-unsaturated substrate.

These reactions are thermodynamically controlled reactions. Less reactive Michael acceptors are preferred for conjugate addition reactions. Similarly stabilized enolate also facilitates conjugate addition. The product obtained as a result of Michael addition reaction is called Michael’s adduct.

Michael addition reaction is a very important reaction for the synthesis of 1,5-Difunctionalized compounds. During this reaction, two double bonds are converted into two single bonds. It is the most frequently used reaction for the formation of the C-C bond.

Example of Michael reaction

Michael addition reaction takes place with a variety of reagents i.e, acetylenic esters, 𝛂,𝜷-unsaturated carbonyl, 𝛂,𝜷-unsaturated nitriles, malonates, acetoacetates, 𝜷-ketoesters and other compounds having a double bond in conjugation with electron-withdrawing.

example of michael addition reaction

Mechanism

Michael reaction is three step reaction. It is carried out with conjugated substrates. These reactions are carried out in protic solvents with a catalytic amount of base.

Step 1 (Deprotonation)

The first step of the Michael reaction is deprotonation. In this step, the base attack the acidic hydrogens. It removes one of the hydrogen atoms and generates an enolate anion.

first step of michael addition reaction mechanism

Step 2 (Attack of nucleophile)

Enolate ions generated in the first step act as nucleophiles. It attacks the 𝜷- carbon of 𝛂,𝜷-unsaturated carbonyl compounds. This results in the formation of an enolate anion.

second step of Michael addition reaction mechanism

Step 3 (Protonation)

In this step, the enolate anion removes a proton from the solvent or Michael donor and forms a final product called Michael adduct. Product has original enolate ion bonded through 𝛂 carbon to the 𝜷 carbon of unsaturated Michael acceptor.

third step of Michael addition reaction mechanism

Michael acceptors

Micheal acceptors must have a double bond in conjugation with electron-withdrawing groups. Michael acceptors are toxic and carcinogenic so must be dealt with care. There are different substrates that can act as Michael acceptors. For example,

  • Acetylenic esters
  • 𝛂,𝜷-unsaturated carbonyl
  • 𝛂,𝜷-unsaturated nitriles
  • Malonates
  • Acetoacetates
  • 𝜷-ketoesters
  • Nitroethylene
  • Propenamide
  • Methyl cinnamate
  • Diethyl fumarate
  • Acrylonitrile
  • Ethyl vinyl ketone
  • Propenitrile
  • Propenal, etc.

Micheal donors

Any substrate that has acidic hydrogens can act as a Michael donor. Actually, Michael donors are enolate anions also known as carbonion. So the substrate having acidic hydrogen can easily be converted into enolates anions. Acidic hydrogens are also known as active methylenes. These are surrounded by two electron-withdrawing groups. These groups make them very reactive. For example,

  • Dicarboxylic acids
  • Nitro compounds
  • Diesters
  • Ketones
  • 𝜷-ketoesters
  • Esters
  • Enamines
  • 𝜷-diketones
  • Diethyl malonate, etc.

Factors affecting Michael reaction

There are two main factors that affect the Michael reaction

  • Stability of enolate

Enolates are formed by the removal of acidic hydrogens from the Michael donor. The stability of enolate greatly affects Michael reaction. In the case of a stable enolate, conjugate addition is preferred whereas unstable enolates favor direct addition reactions

  • Reactivity of Michael acceptors

The reactivity of Michael acceptor also affects Michael reaction. The less reactive Michael acceptors favor the conjugate addition or 1,4-addition whereas more reactive Michael acceptors favor 1,2-addition or direction addition reactions. So less electrophilic carbonyl compounds are preferable for Michael reaction.

Asymmetric Micheal addition reaction

Asymmetric Michael addition is an enantioselective reaction. One of the enantiomers is formed in excess. This involves the syn addition of groups. A chiral catalyst for asymmetrical synthesis i.e proline derivatives, etc. In this synthesis prochiral compounds are converted into chiral compounds. For example,

asymmetric michael addition reaction

Reaction following Micheal mechanism

  • Robinson Annulation reaction
  • The Stork reaction

Concepts berg

Why is a very small amount of base is required for Michael reaction?

Michael reaction requires a very small amount of base because the enolate ion itself is a base and capable to deprotonate carbonyl compounds.

Or when the excess base is used it produces more enolate anion that shifts the reaction in a reverse direction.

What are Michael acceptors ? give their examples.

Michal acceptors are the 𝛂,𝜷-unsaturated compounds having electron-withdrawing in conjugation. For example, acetylenic esters, 𝛂,𝜷-unsaturated carbonyl, 𝛂,𝜷-unsaturated nitriles, Malonates, Acetoacetates, 𝜷-ketoesters, etc.

Why is Michael reaction called 1,4 conjugate addition reaction?

Because atoms are added at position 1 and position 4 of the Michael acceptors.

Why do enolate attack at 𝜷-carbon rather than carbonyl carbon?

Because the 𝜷-carbon is easily approachable and more electrophilic center than carbonyl carbon.

What are Michael donors give their examples?

Michael donors are nucleophiles having acidic hydrogen and can easily be converted to enolate anion. For example, Dicarboxylic acids, Nitro compounds, Diesters, Ketones, Enamines, 𝜷-diketones, etc.

What is meant by active hydrogens?

These are highly reactive hydrogen due to two electron-withdrawing groups attached to the same carbon atom bonded to these hydrogens. These are easy to remove. For example,

acidic hydrogens or active methylene

What is Mukaiyama-Michael’s addition?

What are asymmetric Michael reactions?

How can you tell a Michael acceptor

Which is the best Michael acceptor

Why do alkenes undergo addition reactions

Why is addition faster than a substitution reaction

References

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