Remote functionalization through alkene isomerization

Abstract

Exploiting the reactivity of one functional group within a molecule to generate a reaction at a different position is an ongoing challenge in organic synthesis. Effective remote functionalization protocols have the potential to provide access to almost any derivatives but are difficult to achieve. The difficulty is more pronounced for acyclic systems where flexible alkyl chains are present between the initiating functional group and the desired reactive centres. In this Review, we discuss the concept of remote functionalization of alkenes using metal complexes, leading to a selective reaction at a position distal to the initial double bond. We aim to show the vast opportunity provided by this growing field through selected and representative examples. Our aim is to demonstrate that using a double bond as a chemical handle, metal-assisted long-distance activation could be used as a powerful synthetic strategy.

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Figure 1: The concept of remote functionalization.
Figure 2: General mechanisms for the transition-metal mediated isomerization of olefins.
Figure 3: Selected examples of terminal functionalization of internal olefins.
Figure 4: Selected examples of remote functionalization triggered by hydrometallation.
Figure 5: Selected examples of remote functionalization induced by chain-walking processes and triggered by an initial Heck addition step.
Figure 6: Selected examples of remote construction of new C–C (or C–X) bonds through a metal-mediated 1,3-hydrogen shift.
Figure 7: Transition-metal mediated remote cleavage of C–C bonds.

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Acknowledgements

This research was supported by the European Research Council under the Seventh Framework Program of the European Community (ERC grant agreement no 338912). I.M. holds the Sir Michael and Lady Sobell Academic Chair.

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A.V., J.B. and I.M. contributed to discussions and wrote the manuscript.

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Correspondence to Ilan Marek.

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Vasseur, A., Bruffaerts, J. & Marek, I. Remote functionalization through alkene isomerization. Nature Chem 8, 209–219 (2016). https://doi.org/10.1038/nchem.2445

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