Michael reaction

The Michael addition reaction is a name in the organic chemistry. The reaction was named after the American chemist Arthur Michael ( 1853-1942 ). It is often used for the formation of carbon- carbon single bonds, but is not limited thereto. It can be, for example, also make carbon-sulfur, carbon-oxygen or carbon -nitrogen bonds.

Overview reaction

It is an addition to an α, β -unsaturated carbonyl compound ( Michael acceptor ), such as α, β -unsaturated aldehydes, ketones, esters or carboxamides. An α, β - unsaturated nitriles - for example, acrylonitrile - can likewise be a Michael addition ..

The attacking agent ( Michael donor ) must be relatively soft nucleophilic and after the HSAB concept. Suitable compounds that can be added are carbanions, that is, by adding a base in the α -position of carbonyl deprotonated. In the following example, the newly formed CC bond is highlighted in red:

As nucleophiles, for example, organic copper compounds, amines, thiols, phenolate ions or cyanide can be used from prussic acid. It used to be led by the Michael addition exclusively in a protic solvent ( such as alcohol ) and sat as a base the corresponding alkoxides. Due to the transition to an aprotic solvent (example: wasserfreiesTHF ) and sterically hindered and non- nucleophilic base ( Example: LDA), the range of applications for the Michael addition has been significantly expanded.

Reaction mechanism

In the first step of the Michael donor (here: an ester ) by a base (here hydroxide ) deprotonated and it is just water. In the course of the resulting anion reacts with the Michael acceptor ( here: an α, β -unsaturated ketone ). Then is then formed by protonation and tautomerization of the Michael adduct.

In the case of protic solvents, the enolate obtained as the primary product is protonated and stopped further reaction. If we introduce, however, the Michael addition in an aprotic medium by the enolate may lead to further reactions. This can be exploited quite well by, another and now intramolecular Michael -acceptor provides the, resulting in the Michael reaction enolate. In this way, the appearance of a complex bicyclo [2.2.2] octane ring system is easily possible, for example, by reacting a Dienolations of cyclohexadiene derivatives with acrylic acid esters. Structures of this type are used as starting compound for the synthesis of complex terpenes in the context of natural product syntheses of importance.

The Michael addition reaction is an important reaction in the group transfer polymerization (GTP ).

Enantioselective Michael addition

Numerous embodiments of the enantioselective Michael addition are known, among other things includes the following reactions:

  • Addition of ketones or aldehydes to nitroalkenes or enones
  • Addition of malonates to nitroalkenes or enones
  • Addition of diethylzinc to nitroalkenes or enones
  • Addition of N- Hetrerocyclen or aldehydes to nitroalkenes or enones
  • Addition of α - hydroxy ketones or aldehydes to nitroalkenes or enones
  • Addition of arylboronic acids

Technical application

The addition of methyl mercaptan ( methanethiol ) to the carbon-carbon double bond of acrolein, resulting in methylmercaptopropionaldehyde (MMP ), an intermediate for the production of economically important DL -methionine. From this feed additive more than 100,000 tonnes per year are produced.

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