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Further Information

Related Reactions
Aldol Condensation
Henry Reaction
Mukaiyama Aldol Addition
β-Hydroxy ketones

Aldol Addition
Aldol Reaction

'Aldol' is an abbreviation of aldehyde and alcohol. When the enolate of an aldehyde or a ketone reacts at the α-carbon with the carbonyl of another molecule under basic or acidic conditions to obtain β-hydroxy aldehyde or ketone, this reaction is called Aldol Reaction.

Mechanism of the Aldol Addition

Under conditions of kinetic control, the mixed Aldol Addition can be used to prepare adducts that are otherwise difficult to obtain selectively. This process begins with the irreversible generation of the kinetic enolate, e.g. by employing a sterically hindered lithium amide base such as LDA (lithium diisopropylamide). With an unsymmetrically substituted ketone, such a non-nucleophilic, sterically-demanding, strong base will abstract a proton from the least hindered side. Proton transfer is avoided with lithium enolates at low temperatures in ethereal solvents, so that addition of a second carbonyl partner (ketone or aldehyde) will produce the desired aldol product.

Recent Literature

Highly Enantioselective Organocatalytic Direct Aldol Reaction in an Aqueous Medium
V. Maya, M. Raj, V. K. Singh, Org. Lett., 2007, 9, 2593-2595.

Chiral Amine-Polyoxometalate Hybrids as Highly Efficient and Recoverable Asymmetric Enamine Catalysts
S. Luo, J. Li, H. Xu, L. Zhang, J.-P. Cheng, Org. Lett., 2007, 9, 3675-3678.

Improved Conditions for the Proline-Catalyzed Aldol Reaction of Acetone with Aliphatic Aldehydes
A. Martínez, K. Zumbansen, A. Döhring, M. van Gemmeren, B. List, Synlett, 2014, 25, 932-934.

A Highly Efficient Organocatalyst for Direct Aldol Reactions of Ketones with Aldedydes
Z. Tang, Z.-H. Yang, X.-H. Chen, L.-F. Cun, A.-Q. Mi, Y.-Z. Jiang, L.-Z. Gong, J. Am. Chem. Soc., 2005, 127, 9285-9289.

The First Direct and Enantioselective Cross-Aldol Reaction of Aldehydes
A. B. Northtrup, D. W. C. MacMillan, J. Am. Chem. Soc., 2002, 124, 6798-6799.

Ligand-Promoted, Boron-Mediated Chemoselective Carboxylic Acid Aldol Reaction
H. Nagai, Y. Morita, Y. Shimizu, M. Kanai, Org. Lett., 2016, 18, 2276-2279.

Peptide-Catalyzed Highly Asymmetric Cross-Aldol Reaction of Aldehydes to Biomimetically Synthesize 1,4-Dicarbonyls
Z.-H. Du, B.-X. Tao, M. Yuan, W.-J. Qin, Y.-L. Xu, P. Wang, C.-S. Da, Org. Lett., 2020, 22, 4444-4450.

Enantioselective organocatalytic aldehyde–aldehyde cross-aldol couplings. The broad utility of α-thioacetal aldehydes
R. I. Storer, D. W. C. MacMillan, Tetrahedron, 2004, 60, 7705-7714.

Highly Diastereo- and Enantioselective Direct Aldol Reactions in Water
Y. Hayashi, T. Sumiya, J. Takahashi, H. Gotoh, T. Urushima, M. Shoji, Angew. Chem. Int. Ed., 2006, 45, 958-961.

Combined Proline-Surfactant Organocatalyst for the Highly Diastereo- and Enantioselective Aqueous Direct Cross-Aldol Reaction of Aldehydes
Y. Hayashi, S. Aratake, T. Okano, J. Takahashi, T. Sumiya, M. Shoji, Angew. Chem. Int. Ed., 2006, 45, 5527-5529.

Design of Organocatalysts for Asymmetric Direct Syn-Aldol Reactions
X.-Y. Xu, Y.-Z. Wang, L.-Z. Gong, Org. Lett., 2007, 9, 4247-4249.

Chiral Diols: A New Class of Additives for Direct Aldol Reaction Catalyzed by L-Proline
Y. Zhou, Z. Shan, J. Org. Chem., 2006, 71, 9510-9512.

Anti-selective and regioselective aldol addition of ketones with aldehydes using MgI2 as promoter
H.-X. Wei, R. L. Jasoni, H. Shao, J. Hu, P. W. Pare, Tetrahedron, 2004, 60, 11829-11835.

The Aldol Reaction under High-Intensity Ultrasound: A Novel Approach to an Old Reaction
G. Cravotto, A. Demetri, G. M. Nano, G. Palmisano, A. Penoni, S. Tagliapietra, Eur. J. Org. Chem., 2003, 4438-4444.

Reconstructed Hydrotalcite as a Highly Active Heterogeneous Base Catalyst for Carbon-Carbon Bond Formations in the Presence of Water
K. Ebitani, K. Motokura, K. Mori, T. Mizugaki, K. Kaneda, J. Org. Chem., 2006, 71, 5440-5447.

Direct Asymmetric Aldol Reactions of Acetone Using Bimetallic Zinc Catalysts
B. M. Trost, E. R. Silcoff, H. Ito, Org. Lett., 2001, 3, 2497-2500.

Synthesis of β-Hydroxy-α-haloesters through Super Silyl Ester Directed Syn-Selective Aldol Reaction
S. Oda, H. Yamamoto, Org. Lett., 2013, 15, 6030-6033.

Highly Stereoselective TiCl4-Mediated Aldol Reactions from (S)-2-Benzyloxy-3-pentanone
V. Rodríquez-Cisterna, C. Villar, P. Romea, F. Urpi, J. Org. Chem., 2007, 72, 6631-6633.

Development of Highly Diastereo- and Enantioselective Direct Asymmetric Aldol Reaction of a Glycinate Schiff Base with Aldehydes Catalyzed by Chiral Quaternary Ammonium Salts
T. Ooi, M. Kameda, M. Taniguchi, K. Maruoka, J. Am. Chem. Soc., 2004,126, 9685-9694.

Crossed aldol reaction using cross-linked polymer-bound lithium dialkylamide
A. Seki, F. Ishiwata, Y. Takizawa, M. Asami, Tetrahedron, 2004, 60, 5001-5011.