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Direct Nucleophilic Substitution of Alcohols by Brønsted or Lewis Acids Activation: An Update

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Green Chemistry in Drug Discovery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Typically substitution of alcohols involves a two-step activation/displacement pathway thus leading to the generation of additional waste. The current chapter considers an alternative reaction manifold with the displacement taking place directly through activation of the alcohol by either a Lewis or Brønsted acid. With particular focus on the literature since 2011, an initial overview of carbenium ion reactivity is provided followed by a survey of displacement reactions grouped by the nature of the nucleophile. Finally, advances in both diastereoselective and enantioselective variants of the reaction are discussed.

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Authors and Affiliations

  1. Dipartimento di Chimica “G. Ciamician”, ALMA MATER STUDIORUM, Università di Bologna, Bologna, Italy

    Pier Giorgio Cozzi, Andrea Gualandi, Luca Mengozzi & Elisabetta Manoni

  2. School of Chemistry, Faculty of Science, Agriculture and Engineering, Newcastle University, Newcastle upon Tyne, UK

    Claire Margaret Wilson

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  1. Pier Giorgio Cozzi
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  2. Andrea Gualandi
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  3. Luca Mengozzi
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  4. Elisabetta Manoni
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  5. Claire Margaret Wilson
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Correspondence to Pier Giorgio Cozzi .

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  1. World Wide Medicinal Chemistry, Pfizer Inc., San Diego, CA, USA

    Paul F. Richardson

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Cozzi, P.G., Gualandi, A., Mengozzi, L., Manoni, E., Wilson, C.M. (2022). Direct Nucleophilic Substitution of Alcohols by Brønsted or Lewis Acids Activation: An Update. In: Richardson, P.F. (eds) Green Chemistry in Drug Discovery. Methods in Pharmacology and Toxicology. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1579-9_4

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  • DOI: https://doi.org/10.1007/978-1-0716-1579-9_4

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