The Tishchenko Reaction

Ari M.P. Koskinen, Antti O. Kataja

    Research output: Chapter in Book/Report/Conference proceedingChapterScientificpeer-review

    15 Citations (Scopus)

    Abstract

    Aldehydes may be dimerized to symmetric esters via the Tishchenko reaction. This process is traditionally catalyzed by aluminum alkoxides, but a wide variety of different metal catalysts has been explored and implemented, ranging from simple alkali metal compounds to actinoid complexes. The mechanistic key step is a hydride transfer from a hemiacetal intermediate to an aldehyde, both participants being coordinated to the metal catalyst in the transition state. Recent research on the Tishchenko reaction has especially focused on the controlled synthesis of unsymmetrical esters. In the aldol-Tishchenko variant, an aldol reaction takes place first between two aldehydes, or a ketone and an aldehyde. In the subsequent Tishchenko step, another aldehyde molecule coordinates to the aldol product, forming a hemiacetal intermediate. An intramolecular hydrogen transfer from the hemiacetal to the carbonyl group takes place, giving a 1, 3-diol monoester product. With -hydroxy ketone substrates, the reaction is highly diastereoselective towards 1, 3-anti-diols due to a highly organized six-membered transition state promoted by coordination of a metal catalyst to both the hemiacetal and carbonyl groups. Thus, recent research has strongly focused on the development of direct catalytic asymmetric aldol-Tishchenko reactions. The Evans-Tishchenko reaction is a further variant of the aldol-Tishchenko reaction, being used to reduce preformed -hydroxy ketones to anti-1, 3-diols under relatively mild conditions. This method is applied to various total syntheses of natural products. Samarium iodide is commonly used as the catalyst, and nearly any aldehyde is suitable as the reducing agent. The reaction has also been exploited in a reverse fashion to oxidize complex aldehydes to carboxylic acids using a simple sacrificial -hydroxy ketone as the oxidant. This review covers the literature from the discovery of the Tishchenko reaction in 1887 up to early 2014. Different catalyst systems for both Tishchenko and aldol-Tishchenko reactions are discussed and compared in the “Scope and Limitations” section, and the state of the art in substrate complexity for the reaction is presented in the “Tabular Survey”.

    Original languageEnglish
    Title of host publicationOrganic Reactions
    PublisherJohn Wiley and Sons Inc.
    Pages105-409
    Number of pages305
    Volume86
    Edition1
    DOIs
    Publication statusPublished - 2015
    MoE publication typeA3 Part of a book or another research book

    Publication series

    NameOrganic Reactions
    Number1
    Volume86
    ISSN (Print)0078-6179

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