Tishchenko Reaction

The Tishchenko Reaction is a disproportionation reaction that allows the preparation of esters from two equivalents of an aldehyde.

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Mechanism of the Tishchenko Reaction

The aluminium alkoxide acts as a Lewis acid to coordinate with one molecule of the aldehyde, and to facilitate the addition of a second equivalent of aldehyde, generating a hemiacetal intermediate:

This species undergoes an intramolecular 1,3-hydride shift that results in the production of the aluminium-coordinated ester.

A potential side reaction is the involvement of one of the alkoxide groups from the catalyst:

This can be minimised, if the reaction is conducted at low temperatures and low catalyst loadings.

Recent Literature

Nickel-Catalyzed Selective Conversion of Two Different Aldehydes to Cross-Coupled Esters
Y. Hoshimoto, M. Ohashi, S. Ogoshi, J. Am. Chem. Soc., 2011, 133, 4668-4671.

The Thiolate-Catalyzed Intermolecular Crossed Tishchenko Reaction: Highly Chemoselective Coupling of Two Different Aromatic Aldehydes
S. P. Curran, S. J. Connon, Angew. Chem. Int. Ed., 2012, 51, 10866-10870.

Lithium Bromide as a Flexible, Mild, and Recyclable Reagent for Solvent-Free Cannizzaro, Tishchenko, and Meerwein-Ponndorf-Verley Reactions
M. M. Mojtahedi, E. Akbarzadeh, R. Sharifi, M. S. Abaee, Org. Lett., 2007, 9, 2791-2793.

Catalytic Meerwein-Ponndorf-Verley (MPV) and Oppenauer (OPP) Reactions: Remarkable Acceleration of the Hydride Transfer by Powerful Bidentate Aluminum Alkoxides
T. Ooi, T. Miura, Y. Itagaki, H. Ichikawa, K. Maruoka, Synthesis, 2002, 279-291.

Selenide Ions as Catalysts for Homo- and Crossed-Tishchenko Reactions of Expanded Scope
S. P. Curran, S. J. Connon, Org. Lett., 2012, 14, 1074-1077.

Rare Earth Amide-Catalyzed Direct Thioesterification of Aldehydes with Thiols under Mild Conditions
N. Ismaeel, S. Imran, X. Zhu, J. Chen, D. Yuan, Y. Yao, Org. Lett., 2023, 25, 8672-8676.

Stereoselective Synthesis of δ-Lactones from 5-Oxoalkanals via One-Pot Sequential Acetalization, Tishchenko Reaction, and Lactonization by Cooperative Catalysis of Samarium Ion and Mercaptan
J.-L. Hsu, J.-M. Fang, J. Org. Chem., 2001, 66, 8573-8584.

Nucleophile- or Light-Induced Synthesis of 3-Substituted Phthalides from 2-Formylarylketones
D. C. Gerbino, D. Augner, N. Slavoy, H.-G. Schmalz, Org. Lett., 2012, 14, 2338-2341.

Direct Catalytic Asymmetric Aldol-Tishchenko Reaction
V. Gnanadesikan, Y. Horiuchi, T. Ohshima, M. Shibasaki, J. Am. Chem. Soc., 2004, 126, 7782-7783.