Michael addition

Michael addition is a widely utilized chemical reaction in organic chemistry, named after the American chemist Arthur Michael. This reaction involves the 1,4-addition (or conjugate addition) of a carbon nucleophile to an α,β-unsaturated carbonyl compound. The Michael addition is a key step in the construction of various molecules, ranging from small organic compounds to complex natural products.

Mechanism

The Michael addition reaction mechanism typically involves the attack of a nucleophilic species, such as an enolate, cyanide, thiol, or nitronate, on an electrophilic α,β-unsaturated carbonyl compound. The nucleophile attacks the β-carbon of the carbonyl compound, which has an electron deficiency due to the conjugation with the carbonyl group. This results in the formation of a new carbon-carbon bond.

Applications

The Michael addition is fundamental in the synthesis of many pharmaceuticals, agrochemicals, and polymers. It is also employed in the creation of cyclic compounds and is a key step in the total synthesis of various natural products. Due to its versatility and the wide availability of both Michael donors and acceptors, this reaction is highly valuable in the field of medicinal chemistry and material science.

Variants

Several variants of the Michael addition exist, including the asymmetric Michael addition, which is used to create chiral centers in an enantioselective manner. This variant often employs chiral auxiliaries or catalysts to induce stereoselectivity, crucial for the production of enantiomerically pure substances in the pharmaceutical industry.

See also

• Organic synthesis
• Catalysis
• Enantioselective synthesis
• List of organic reactions