Methyl Radical Addition Reactions to C═X Double Bonds
Radical additions to olefins and related π-systems are essential tools in the modern synthetic toolbox for forging C-C and C-X bonds. We report a systematic DFT study (ZORA-(U)OLYP/TZ2P) on methyl radical (H<sub>3</sub>C<sup>•</sup>) additions to H<sub>2</sub>C═X substrates, where X is varied across elements from the tetrel (group 14: C, Si, Ge), pnictogen (group 15: N, P, As), and chalcogen (group 16: O, S, Se) groups. Our analysis reveals clear periodic trends: addition barriers at carbon decrease, and those at X increase from tetrels to chalcogens; reaction energies become less favorable across a period but more favorable down a group. Regioselectivity favors addition at X except for X = CH<sub>2</sub>, NH, and O, where carbon attack dominates─consistent with experimental data. These trends arise from a balance of orbital interactions and Pauli repulsion, with the latter emerging as a key, yet underappreciated, factor governing radical reactivity and regioselectivity in π-systems.
Authors
- Christopher B. Kelly (ORCID: https://orcid.org/0000-0002-5530-8606)
- Trevor A. Hamlin (ORCID: https://orcid.org/0000-0002-5128-1004)
- Yuman Hordijk (ORCID: https://orcid.org/0000-0002-0777-4274)
- Bart Waaijer
Institutions
- Johnson & Johnson (United States) (US)
- Discovery Centre (CA)
- Discovery Laboratories (United States) (US)
- Johnson & Johnson (Israel) (IL)
- Vrije Universiteit Amsterdam (NL)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2025-07-21
- DOI
- https://doi.org/10.1021/acs.joc.5c01157
- Citations
- 3
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 2.81