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Record W4409215944 · doi:10.1021/acs.joc.5c00092

Hydrogen Atom Transfer-Based C(sp<sup>3</sup>)–H Bond Oxygenation of Lactams and Cycloalkenes: The Influence of Ring Size on Reactivity and Site Selectivity

2025· article· en· W4409215944 on OpenAlexaff
Sergio Sisti, Fabio Ioele, Filippo Scarchilli, Simona Laparelli, Marco Galeotti, Omid Hosseinzadeh, Gino A. DiLabio, Michela Salamone, Massimo Bietti

Bibliographic record

VenueThe Journal of Organic Chemistry · 2025
Typearticle
Languageen
FieldChemistry
TopicCatalytic C–H Functionalization Methods
Canadian institutionsUniversity of British Columbia, Okanagan CampusUniversity of British Columbia
FundersMinistero dell'Università e della Ricerca
KeywordsChemistryReactivity (psychology)SelectivityRing sizeRing (chemistry)Hydrogen bondHydrogen atomMedicinal chemistryStereochemistryOrganic chemistryCatalysisMoleculeGroup (periodic table)

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide Kinetic and product studies on the reactions of the cumyloxyl (CumO • ) and tert -butoxyl ( t BuO • ) radicals with secondary and tertiary N -methyl and N -benzyl lactams and with cycloalkenes, accompanied by BDE calculations of the substrate C–H bonds involved in these reactions, are reported. Within the lactams, the rate constants for HAT ( k H ) from the C–H bonds to CumO • decrease by a factor ∼4 going from the 5- and 6-membered derivatives to the 8-membered ones. Product distributions obtained through oxygenation initiated by t BuO • show that HAT preferentially occurs from the most electron-rich α-C–H bonds, with site selectivity that, within the N -methyl and N -benzyl series, progressively shifts from the endocyclic to the exocyclic α-C–H bonds with increasing ring size, indicative of deactivation of the former bonds that, for the 8-membered derivatives, translates into competitive oxygenation at different sites. Similar trends have been observed for the corresponding reactions of the cycloalkenes, with k H values that decrease by a factor of ∼4 together with site selectivity for HAT from the activated allylic C–H bonds, going from cyclopentene to cyclooctene. It is proposed that the greater flexibility of the medium-sized rings decreases the extent of hyperconjugative overlap between the α-C–H bonds and the amide or C═C π-systems, increasing the kinetic barrier for HAT from these sites, with decreases in reactivity that approach factors of 83 and 18, for the endocyclic α-C–H bonds of tertiary N -methyl lactams and the allylic C–H bonds of cycloalkenes, respectively.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.007
GPT teacher head0.240
Teacher spread0.233 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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

Citations4
Published2025
Admission routes1
Has abstractyes

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