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Activation of polar organometallic reagents with alkali-metal alkoxides

Nature Synthesis volume 1, pages 195–202 (2022)Cite this article

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Abstract

The use of group 1 metal alkoxides as additives to activate s-block organometallics is an established phenomenon in polar organometallic chemistry. Typified by the Lochmann–Schlosser superbase, these reagents have proved to be exceptionally powerful bases for the deprotonative metallation of organic substrates. However, despite their long-standing importance in synthesis, the nature of this activating effect remains to be fully understood. Here we shed light on the origins of the special reactivities of which these reagents are capable, which generally cannot be replicated by their homometallic precursors. In addition, reactivity studies that have established the mixed-metal constitutions of these organometallic reagents are discussed. Opening up new directions in synthesis, the use of lithium alkoxides as additives to promote direct regioselective magnesium (or zinc)/halogen exchange processes to access highly functionalized organometallics is also discussed, with an emphasis on rationalizing the role of each metal in these transformations.

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Fig. 1: Synthesis and reactivity of superbase reagents.
Fig. 2: Mixed-metal constitution of RLi/AM-OR combinations.
Fig. 3: Select examples of Mg/Br exchange using AM-OR-powered magnesiate reagents.
Fig. 4: Understanding the complexity of the [sBu2Mg + LiOR′] exchange reagent.

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Acknowledgements

This work was supported by the Swiss National Science Foundation (SNF, grant no. 188573) and the University of Bern. We also thank R. E. Mulvey (University of Strathclyde) and M. Uzelac (University of Edinburgh) for their valuable comments and suggestions.

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  1. Universität Bern, Departement für Chemie, Biochemie und Pharmazie, Bern, Switzerland

    Leonie J. Bole & Eva Hevia

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L.J.B. and E.H. contributed to discussions and wrote the manuscript.

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Correspondence to Eva Hevia.

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Nature Synthesis thanks Florence Mongin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Thomas West was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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Bole, L.J., Hevia, E. Activation of polar organometallic reagents with alkali-metal alkoxides. Nat Synth 1, 195–202 (2022). https://doi.org/10.1038/s44160-022-00040-5

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