Michael Reaction

Definition:

Base-promoted conjugate addition of carbon nucleophiles (donors) to activated unsaturated systems (acceptors):             

Frequency of appearance:

        This bar graph represents all of the online articles that were found to contain this specific name reaction in the title of the article. Tetrahedron letters, Tetrahedron, Synthetic letters, Synthesis, Journal of Organic Chemistry and Journal of the American Chemical Society are represented here. This table by no means represents the periodicity of the name reaction found in the literature.

Original Reference:

1. Michael, A. J. Prakt. Chem., 1887, 35, 379.

Recent academic references: Click here for more references

2. Michael reactions in water using Lewis acid_¯surfactant-combined catalysts

• Yuichiro Mori, Kentaro Kakumoto, Kei Manabe and Shu Kobayashi Tetrahedron Letters, Volume 41, Issue 17, 2000, 3107-3111

3. A Direct Route to Biologically Active Kainic Acid Analogs

• Maeda, H.; Kraus, G.A.* J. Org. Chem., 1997, 62, 2314-2315.

Recent process papers:

4. A practical large-scale synthesis of enantiomerically pure 3-[bis(methoxycarbonyl)methyl]cyclohexanone via catalytic asymmetric Michael reaction

• Youjun Xu, Ken Ohori, Takashi Ohshima and Masakatsu Shibasaki Tetrahedron, Volume 58, Issue 13, 25 March 2002, Pages 2585-2588

Mechanism:

Scope an Limitations:

• Generally protic solvents (alcohols) with alkoxide bases are used. ^A+B
• Transition metal compounds, acidic conditions, electrochemical, Pd catalyzed, water promoted and  ultrasound have also been used to engender Michael products. ^A
• Generally low temperatures are employed.
• Knoevenagel and aldol may competitive side reaction. ^A+B
• Diastereoselectivity general trends: E enolate with Z acceptor = Syn; Z enolate with Z acceptor = anti; E enolate with E acceptor = syn; Z enolate with E acceptor = anti. ^A+B
• Some michael reactions may require elevated pressures. ^B

Synonyms:

• Michael addition
• Conjugate addition