Methyl Radical Addition Reaction to Substituted C=C Double Bonds

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Radical addition reactions have become an indispensable tool for constructing carbon-carbon bonds in organic chemistry. Given the significance of these processes, it is imperative that the underlying rules governing odd electron C-C bond forming processes are better understood. This study explores the fundamental case of methyl radical addition reaction (MRAR) to monosubstituted ethylene derivatives (H2C=CHR, with R = H, CHO, and NMe2) using Density Functional Theory at ZORA-(U)OLYP/TZ2P. We quantitatively analyzed the factors governing regioselectivity and substituent effects using the Activation Strain Model and Energy Decomposition Analysis. Regarding regioselectivity, radical addition@ is universally favored over addition@ due to reduction in the buildup of unfavorable Pauli repulsion (ΔEPauli) and maximization of orbital interactions (ΔEoi) with the -carbon. Substituents modulate reactivity through electronic effects: both electron-donating groups (EDGs) like NMe2 and electron-withdrawing groups (EWGs) like CHO lower activation barriers with respect to the unsubstituted reactions due to improved orbital interactions. Among the substituents, the EWG lowers the activation barriers more than the EDG due to a change in the orbital interaction mechanism. By linking qualitative theories like Frontier Molecular Orbital Theory with detailed computational insights, this work advances the mechanistic understanding of radical addition reactions and provides a physically sound and intuitive basis for understanding these key transformations.

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