Michael reaction



The Michael reaction or Michael addition is the conjugate additions. This is one of the most useful methods for the mild formation of C-C bonds. Many asymmetric variants exist.[1][2]

In this scheme the R and R' enone but it can also be a nitro group.

Definition

As originally defined by Michael,[3] the reaction is the addition of an enolate of a ketone or aldehyde to an α,β-unsaturated carbonyl compound at the β carbon. A newer definition, proposed by Kohler,[4] is the 1,4-addition of a doubly stabilized carbon nucleophile to an α,β-unsaturated carbonyl compound. Some examples of nucleophiles include beta-ketoesters, malonates, and beta-cyanoesters. The resulting product contains a highly useful 1,5-dioxygenated pattern.

Classical examples of the Michael reaction are the reaction between diethyl malonate (Michael acceptor) and diethyl fumarate,[5] that of methyl vinyl ketone.[10]

The Michael addition is an important Robinson annulation.

Mechanism

The reaction mechanism is 1 (with R an alkoxy residue) as the nucleophile:

Deprotonation of 1 by base leads to conjugate addition reaction. Proton abstraction from protonated base (or solvent) by the enolate 4 to 5 is the final step.

The course of the reaction is dominated by orbital, rather than electrostatic, considerations. The frontier orbitals are of similar energy, and react efficiently to form a new carbon-carbon bond.

Like the catalytic in base. In most cases, the reaction is irreversible at low temperature, due to least-motion arguments.[clarify]

Asymmetric Michael reaction

Recent research has focused on expanding the scope of proline.

In the reaction between p-toluenesulfonic acid:[11]

hydrogen bonded to the protonated amine in the proline side group.

Mukaiyama-Michael Addition

In the Mukaiyama-Michael Addition the nucleophile is an titanium tetrachloride:[12][13]

References

  1. ^ Ian Hunt. Chapter 18: Enols and Enolates — The Michael Addition reaction. University of Calgary.
  2. ^ Clayden et al, Organic Chemistry
  3. ^ Michael, Arthur. J. Prakt. Chem. 1887, 36, 349-356; ibid., 1894, 49, 20
  4. ^ Kohler. (J. Am. Chem. Soc., 1907, 37, 385; ibid., 1935, 57, 1316.
  5. ^ H. T. Clarke and T. F. Murray (1941). "1,1,2,3-Propanetetracarboxylic acid, tetraethyl ester". Org. Synth.; Coll. Vol. 1: 272. 
  6. ^ R. L. Shriner and H. R. Todd (1943). "1,3-Cyclohexanedione, 5,5-dimethyl-". Org. Synth.; Coll. Vol. 2: 200. 
  7. ^ James Cason (1963). "β-Methylglutaric anhydride". Org. Synth.; Coll. Vol. 4: 630. 
  8. ^ R. B. Moffett (1963). "Methyl γ-Methyl-γ-nitrovalerate". Org. Synth.; Coll. Vol. 4: 652. 
  9. ^ E. C. Horning and A. F. Finelli (1963). "α-Phenyl-α-carbethoxyglutaronitrile". Org. Synth.; Coll. Vol. 4: 776. 
  10. ^ (1988) "Conversion of Nitro to Carbonyl by Ozonolysis of Nitronates: 2,5-Heptanedione". Org. Synth.; Coll. Vol. 6: 648. 
  11. ^ Sunil V. Pansare and Keyur Pandya (2006). "Simple Diamine- and Triamine-Protonic Acid Catalysts for the Enantioselective Michael Addition of Cyclic Ketones to Nitroalkenes" (Communication). J. Am. Chem. Soc. 128 (30): 9624 - 9625. doi:10.1021/ja062701n.
  12. ^ Mukaiyama, T. (1977). "Titanium Tetrachloride in Organic Synthesis [New synthetic methods (21)]" (Review). Angew. Chem., Int. Ed. Engl. 16: 817-826. doi:10.1002/anie.197708171.
  13. ^ Alex R. Lippert, Juthanat Kaeobamrung, and Jeffrey W. Bode (2006). "Synthesis of Oligosubstituted Bullvalones: Shapeshifting Molecules Under Basic Conditions" (Communication). J. Am. Chem. Soc. 128 (46): 14738 - 14739. doi:10.1021/ja063900+.
 
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