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Merging C–H and C–C bond cleavage in organic synthesis

Abstract

Metal-catalysed functionalization of a carbon–hydrogen bond can occur selectively even in the presence of ostensibly more reactive functional groups. Such conversions have changed our perceptions of organic chemistry because we can now consider a C–H bond as a functional group, the reactions of which are among the most attractive and powerful means to rapidly add complexity. Another versatile tool in organic synthesis is the metal-catalysed selective cleavage of C–C bonds. Applying both expedient methods in a tandem process would give us an ideal approach to synthesizing complex molecular architectures. The challenge lies in ensuring that the reactions do not interfere with each other; the simultaneous control of both C–H and C–C bond activations is the subject of this Review. The reactions that meet this challenge and enable a selective merger of C–H and C–C bond activations in a one-pot process are discussed. Their realization could afford sophisticated molecular fragments that are otherwise difficult to access.

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Figure 1: The concept of merging C–H and C–C bond cleavage.
Figure 2: Norbornene mediates C–H and C–C bond cleavage of aryl iodides in the Catellani reaction.
Figure 3: Norbornene derivatives mediate C–H and C–C bond cleavage of arenes.
Figure 4: CO2 as a mediating group in Pd-catalysed C–H and C–C bond cleavage.
Figure 5: Alkene functionality as an internal mediator in tandem C–H and C–C bond cleavage.
Figure 6: Early work in the tandem activation of a cyclopropane derivative.
Figure 7: Tandem C–H and C–C cleavage in cyclopropane derivatives.
Figure 8: Tandem C–C and C–H cleavage in cyclopropanes.
Figure 9: Tandem C–H and C–C cleavage in cyclobutane derivatives.
Figure 10: Tandem C–C and C–H cleavage in cyclobutane derivatives.
Figure 11: Selected examples of tandem C–H and C–C cleavage in unstrained molecules.
Figure 12: Miscellaneous tandem C–H and C–C activation reactions.
Figure 13: Selected applications of tandem C–H and C–C cleavage reactions.

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Acknowledgements

This research was supported by the European Research Council under the Seventh Framework Programme of the European Community (ERC grant agreement number 338912). I.M. holds the Sir Michael and Lady Sobell Academic Chair.

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Correspondence to Ilan Marek.

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Nairoukh, Z., Cormier, M. & Marek, I. Merging C–H and C–C bond cleavage in organic synthesis. Nat Rev Chem 1, 0035 (2017). https://doi.org/10.1038/s41570-017-0035

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