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Radical philicity and its role in selective organic transformations

Abstract

Radical intermediates in organic chemistry lack a full octet of electrons and, thus, are commonly said to be electron deficient. By denotation, such a statement is technically correct; however, in modern literature, the term ‘electron deficient’ carries a connotation of electrophilicity. This lexical quirk leads one to predict that all radicals should behave as electrophiles, when this is not the case. Indeed, practitioners of radical chemistry have known for decades that many radicals behave as nucleophiles, sometimes strongly so. This Review aims to establish guidelines for understanding radical philicity by highlighting examples from recent literature as a demonstration of general reactivity paradigms across a series of different carbon-based and heteroatom-based radicals. We present strategies for predicting the philicity of a given radical on the basis of qualitative features of the radical’s structure. Finally, we discuss the implications of radical philicity to selective hydrogen atom transfer.

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Fig. 1: The importance of understanding radical philicity.
Fig. 2: Philicity of carbon-centred alkyl radicals.
Fig. 3: Reactivity and philicity of carbon-centred radicals with α-heteroatoms.
Fig. 4: Philicity of sp and sp2 hybrid radicals.
Fig. 5: Philicity of heteroatom-centred radicals.
Fig. 6: Flow chart of radical philicity, including carbon-centred and heteroatom-centred radicals.
Fig. 7: The origin of polar effects in hydrogen atom transfer and polarity-reversal catalysis.

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Acknowledgements

This work was supported by the Cancer Prevention and Research Institute of Texas (grant no. RR190084) and startup funds from the University of Texas at Dallas.

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E.R.W. conceived and directed the project. All authors contributed to the writing and editing of the manuscript prior to submission; F.P., M.C.S., P.B.K., S.N.A. and P.D.E.A. contributed equally.

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Correspondence to Eric R. Welin.

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Parsaee, F., Senarathna, M.C., Kannangara, P.B. et al. Radical philicity and its role in selective organic transformations. Nat Rev Chem 5, 486–499 (2021). https://doi.org/10.1038/s41570-021-00284-3

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