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Record W2728982395 · doi:10.1021/acs.joc.7b01069

Decoding the Mechanism of Intramolecular Cu-Directed Hydroxylation of sp<sup>3</sup> C–H Bonds

2017· article· en· W2728982395 on OpenAlex
Rachel Trammell, Yi Yang See, Aaron T. Herrmann, Nan Xie, Daniel E. Díaz, Maxime A. Siegler, Phil S. Baran, Isaac Garcia‐Bosch

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueThe Journal of Organic Chemistry · 2017
Typearticle
Languageen
FieldChemistry
TopicMetal-Catalyzed Oxygenation Mechanisms
Canadian institutionsnot available
FundersHewitt FoundationNational Institute of General Medical SciencesAgency for Science, Technology and ResearchWelch Foundation
KeywordsIntramolecular forceDecoding methodsHydroxylationMechanism (biology)ChemistryStereochemistryBondComputer sciencePhysicsBiochemistryAlgorithmEnzymeBusiness

Abstract

fetched live from OpenAlex

The use of copper in directed C–H oxidation has been relatively underexplored. In a seminal example, Schönecker showed that copper and O 2 promoted the hydroxylation of steroid-containing ligands. Recently, Baran ( J. Am. Chem. Soc. 2015, 137, 13776) improved the reaction conditions to oxidize similar substrates with excellent yields. In both reports, the involvement of Cu 2 O 2 intermediates was suggested. In this collaborative article, we studied the hydroxylation mechanism in great detail, resulting in the overhaul of the previously accepted mechanism and the development of improved reaction conditions. Extensive experimental evidence (spectroscopic characterization, kinetic analysis, intermolecular reactivity, and radical trap experiments) is provided to support each of the elementary steps proposed and the hypothesis that a key mononuclear LCu II (OOR) intermediate undergoes homolytic O–O cleavage to generate reactive RO • species, which are responsible for key C–H hydroxylation within the solvent cage. These key findings allowed the oxidation protocol to be reformulated, leading to improvements of the reaction cost, practicability, and isolated yield.

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.

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)0.001
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 score0.008
Threshold uncertainty score0.998

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
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 science0.0020.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.014
GPT teacher head0.238
Teacher spread0.225 · 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