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Stereospecific and stereoconvergent cross-couplings between alkyl electrophiles

Nature Reviews Chemistry volume 1, Article number: 0065 (2017) Cite this article

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Abstract

The development of metal-catalysed cross-coupling reactions between one electrophilic and one organometallic nucleophilic partner has revolutionized the practice of chemical synthesis, with coupling reactions between sp2 centres now commonplace in both academic and industrial research. Methods to allow coupling of sp3 centres are rapidly being developed, with many recent advances even enabling control of the absolute configuration of newly formed stereogenic centres. The related cross-electrophile couplings have not been developed as thoroughly owing to the challenge of obtaining cross-selectivity between two substrates with similar reactivity. However, the discovery of improved methods to address this challenge has led to significant recent progress. The development of enantioselective cross-electrophile coupling reactions is an emerging area of research. Both stereoconvergent and stereospecific variants have been reported for the synthesis of a range of products containing tertiary stereogenic centres. Many of these transformations build on lessons learnt from traditional (electrophile–nucleophile) cross-couplings of alkyl electrophiles. For example, all enantioselective transformations described to date use a nickel catalyst. Continued progression is likely to provide strategic disconnections for asymmetric synthesis of natural products and medicinal agents.

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Figure 1: Variations of cross-coupling reactions.
Figure 2: Typical catalytic cycles for cross-coupling and cross-electrophile coupling reactions.
Figure 3: Radical oxidative addition.
Figure 4: Polar oxidative addition.

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Acknowledgements

This work was supported by the US National Science Foundation (NSF-CHE-1464980).

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  1. Erika L. Lucas and Elizabeth R. Jarvo are at the Department of Chemistry, University of California, Irvine, California 92697–2025, USA.,

    Erika L. Lucas & Elizabeth R. Jarvo

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Correspondence to Elizabeth R. Jarvo.

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Lucas, E., Jarvo, E. Stereospecific and stereoconvergent cross-couplings between alkyl electrophiles. Nat Rev Chem 1, 0065 (2017). https://doi.org/10.1038/s41570-017-0065

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