Radical Learn

Radical philicity

Radicals lack a full octet, but being "electron deficient" does not make them electrophiles. What decides is the energy of the singly occupied orbital (SOMO). Groups that push electron density into it raise it, and the radical is nucleophilic: it reacts fastest with electron-poor partners. Groups that pull density out of it lower it, and the radical is electrophilic (Parsaee and co-workers 2021).

Raise the SOMO: nucleophilic

alkyl groups (hyperconjugation); a lone pair next to the radical centre (α-O, α-N, α-S, and the C=O of an acyl radical); a radical on an atom less electronegative than carbon (B, Si).

Lower the SOMO: electrophilic

π acceptors such as CO₂R and CN (one is enough for a primary radical, a secondary or tertiary one needs two); fluorines (•CF₃); more s character (aryl, vinyl and alkynyl radicals); a radical on an atom more electronegative than carbon (O, N, S, Cl, Br).

Some radicals are ambiphilic, such as aryl, vinyl and •CF₃: they react with both kinds of partner, and the Philicity tab asks which kind they react with most often. The methyl radical is barely polar, but slightly nucleophilic. Polarity also steers hydrogen-atom transfer (HAT): an electrophilic radical (t-BuO•, Cl•, an aminium radical cation) abstracts the electron-rich, "hydridic" C–H next to O or N, whereas a nucleophilic one prefers electron-poor C–H bonds. Choosing the HAT catalyst for this is called polarity-reversal catalysis.

In additions to alkenes, a radical bonds to the less hindered end of the C=C, so that the new radical sits on the more substituted carbon, where it is more stable; this is why HBr with peroxides adds anti-Markovnikov. The Regioselectivity tab asks where additions and HAT take place.

Is there a Mayr scale for radicals?

Not one with measured N and E values that add up in log k = s_N(N + E). Radical additions are fast, and their rates depend on polar and enthalpy effects together: Fischer and Radom described them with the radical's ionisation energy, its electron affinity and the reaction enthalpy (2001), and Héberger and Lopata fitted philicity parameters to measured addition rates (1998). Computed scales exist: De Vleeschouwer, De Proft and co-workers gave electrophilicity and nucleophilicity indices for radicals from vertical ionisation energies and electron affinities, each computed as an energy difference between the radical and its cation or anion (2007). For an open-shell molecule the orbital-energy shortcut used for closed-shell molecules (Koopmans' approximation, I ≈ −ε_HOMO and A ≈ −ε_LUMO) does not give a clean IE or EA, which is why they used energy differences.

References

1. F. Parsaee, M. C. Senarathna, P. B. Kannangara, S. N. Alexander, P. D. E. Arche, E. R. Welin, Radical philicity and its role in selective organic transformations. Nat. Rev. Chem. 2021, 5, 486–499. doi:10.1038/s41570-021-00284-3
2. H. Fischer, L. Radom, Factors controlling the addition of carbon-centered radicals to alkenes: an experimental and theoretical perspective. Angew. Chem. Int. Ed. 2001, 40, 1340–1371.
3. K. Héberger, A. Lopata, Assessment of nucleophilicity and electrophilicity of radicals, and of polar and enthalpy effects on radical addition reactions. J. Org. Chem. 1998, 63, 8646–8653.
4. F. De Vleeschouwer, V. Van Speybroeck, M. Waroquier, P. Geerlings, F. De Proft, Electrophilicity and nucleophilicity index for radicals. Org. Lett. 2007, 9, 2721–2724.

Each answer names the paper it follows; most come from the review by Parsaee and co-workers.