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Record W4416840360 · doi:10.1021/acs.joc.5c02142

Methyl Radical Addition Reaction to Substituted C═C Double Bonds

2025· article· en· W4416840360 on OpenAlexaff
Yuman Hordijk, Tula M. M. Kaptein, Eva Blokker, Christopher B. Kelly, Trevor A. Hamlin

Bibliographic record

VenueThe Journal of Organic Chemistry · 2025
Typearticle
Languageen
FieldChemistry
TopicRadical Photochemical Reactions
Canadian institutionsDiscovery Centre
FundersNederlandse Organisatie voor Wetenschappelijk OnderzoekMicrosoft Research
KeywordsRegioselectivityReactivity (psychology)Density functional theoryDouble bondMolecular orbitalAddition reactionReaction mechanismPauli exclusion principle

Abstract

fetched live from OpenAlex

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 be better understood. This study explores the fundamental case of methyl radical addition reaction (MRAR) to monosubstituted ethylene derivatives (H 2 C β ═C α HR, with R = H, CHO, and NMe 2 ) 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@β is universally favored over addition@α due to reduction in the buildup of unfavorable Pauli repulsion (Δ E Pauli ) and maximization of orbital interactions (Δ E oi ) with the β-carbon. Substituents modulate reactivity through electronic effects: NMe 2 (a representative electron-donating group) and CHO (a representative electron-withdrawing group) lower activation barriers with respect to the unsubstituted reactions due to improved orbital interactions. Among the substituents, CHO lowers the activation barrier for radical addition more than NMe 2 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.039
Threshold uncertainty score0.996

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0050.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.263
Teacher spread0.253 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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