Benzoin Condensation

The Benzoin Condensation is a coupling reaction between two aldehydes that allows the preparation of α-hydroxyketones. The first methods were only suitable for the conversion of aromatic aldehydes.

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Mechanism of Benzoin Condensation

Addition of the cyanide ion to create a cyanohydrin effects an umpolung of the normal carbonyl charge affinity, and the electrophilic aldehyde carbon becomes nucleophilic after deprotonation: A thiazolium salt may also be used as the catalyst in this reaction (see Stetter Reaction).

A strong base is now able to deprotonate at the former carbonyl C-atom:

A second equivalent of aldehyde reacts with this carbanion; elimination of the catalyst regenerates the carbonyl compound at the end of the reaction:

Recent Literature

Chemoselective N-Heterocyclic Carbene-Catalyzed Cross-Benzoin Reactions: Importance of the Fused Ring in Triazolium Salts
S. M. Langdon, M. M. D. Wilde, K. Thai, M. Gravel, J. Am. Chem. Soc., 2014, 136, 7359-7542.

Lanthanum Tricyanide-Catalyzed Acyl Silane-Ketone Benzoin Additions
J. C. Tarr, J. S. Johnson, Org. Lett., 2009, 11, 3870-3873.

Kinetic Control in Direct α-Silyloxy Ketone Synthesis: A New Regiospecific Catalyzed Cross Silyl Benzoin Reaction
X. Linghu, J. S. Johnson, Angew. Chem. Int. Ed., 2003, 42, 2534-2536.

Highly Enantioselective Benzoin Condensation Reactions Involving a Bifunctional Protic Pentafluorophenyl-Substituted Triazolium Precatalyst
L. Baragwanath, C. A. Rose, K. Zeitler, S. J. Connon, J. Org. Chem., 2009, 74, 9214-9217.

An Efficient Nucleophilic Carbene Catalyst for the Asymmetric Benzoin Condensation
D. Enders, U. Kallfass, Angew. Chem. Int. Ed., 2002, 41, 1743-1745.

Highly Chemo- and Enantioselective Cross-Benzoin Reaction of Aliphatic Aldehydes and α-Ketoesters
K. Thai, S. M. Langdon, F. Bilodeau, M. Gravel, Org. Lett., 2013, 15, 2214-2217.

Asymmetric Intramolecular Crossed-Benzoin Reactions by N-Heterocyclic Carbene Catalysis
D. Enders, O. Niemeier, T. Balensiefer, Angew. Chem. Int. Ed., 2006, 45, 1463-1467.