Aldol Reaction

Definition:

Acid or base catalyzed condensation of one carbonyl compound with the enolate/enol of another to generate a ß-hydroxy carbonyl compound.

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. R. Kane, Ann. Phys. Chem., Ser. 2, 44, 475 (1838).

Recent academic references: Click here for more references

2. Boron-Mediated Aldol Reaction of Carboxylic Esters: Complementary Anti- and Syn-Selective Asymmetric Aldol Reactions
   

             Inoue, T.; Liu, J.-F.; Buske, D. C.; Abiko, A.; J. Org. Chem.; 2002; ASAP

3. The First Direct and Enantioselective Cross-Aldol Reaction of Aldehydes
   

             Northrup, A. B.; et al.; J. Am. Chem. Soc.; 124(24); 6798-6799 (2002).

4. Aldol Reaction under Solvent-Free Conditions: Highly Stereoselective Synthesis of 1,3-Amino Alcohols
   

             Loh, T.-P.; et al., Org. Lett; 2(9); 1291-1294 (2000).  

 

Recent process references:

6. Fast Aldol-Tishchenko Reaction Utilizing 1,3-Diol Monoalcoholates as the Catalysts
   Tormakangas, O. P.; Koskinen, A. M. P.;
   Org. Process Res. Dev.; (Article); 2001; 5(4); 421-425.

Mechanism: http://www.arkat.org/arkat/journal/Named Reactions/Aldol.htm

Scope and Limitations:

• Both the aldol reaction and the ensuing dehydration step are reversible depending on reaction conditions. ^B
• Both acid and base may be used to catalyze this reaction. ^{A, B}
• Unsymmetrical ketones and aldehydes with 2 different a -carbons may result in multiple products. ^B
• LDA is often used to initiate a direct aldol reaction between a ketone and aldehyde. ^B

Synonym:

Claisen-Schmidt reaction: crossed aldol reactions (aldehyde with a ketone).

Mukaiyama aldol reaction: aldehydes reacting with trimethylsilyl enol ether using asymmetric Lewis acid catalyst to give an enantioselective product.

Tollens' reaction: Reaction of formaldehyde with an aldehyde or ketone in the presence of a base (usually Ca(OH)₂).