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Record W4407673836 · doi:10.1021/acscatal.5c00428

Intercepting Ketone α-Arylation Intermediates in the DalPhos/Ni-Catalyzed Synthesis of Decorated Benzofurans and NH-Indoles

2025· article· en· W4407673836 on OpenAlexafffund
Joshua W. M. MacMillan, Katherine N. Robertson, Mark Stradiotto

Bibliographic record

VenueACS Catalysis · 2025
Typearticle
Languageen
FieldChemistry
TopicCatalytic C–H Functionalization Methods
Canadian institutionsDalhousie University
FundersNatural Sciences and Engineering Research Council of CanadaKillam TrustsDalhousie University
KeywordsCatalysisKetoneChemistryOrganic chemistryCombinatorial chemistryMedicinal chemistry

Abstract

fetched live from OpenAlex

Employing meso -PAd2-DalPhos ( meso -L1 ) as an ancillary ligand, a single mechanistic landscape provides access to two thermal nickel-catalyzed transformations with broad scope commencing from α-( o -chloro)aryl ketones: the synthesis of 2-substituted benzofurans via intramolecular O -arylation and the synthesis of 3-acyl-2-substituted NH-indoles when incorporating RCN reactants. Through the isolation of intermediates and kinetic analysis, the synthesis of 3-acyl-2-substituted NH-indoles is proposed to occur through a Ni(0/II) catalytic cycle involving: (1) ( meso -L1 )Ni(0) oxidative addition of the aryl chloride; (2) base-facilitated HCl loss forming a Ni(II) κ 2 -C,O enolate species; (3) net addition of the metal-coordinated enolate to the nitrile; and (4) C(sp 2 )–N(sp 2 ) reductive elimination. These mechanistic studies also highlight the influence of base choice on precatalyst activation in such benzofuran syntheses and the impact of RCN electronics on overall catalytic turnover in the formation of NH-indoles, as well as enabling catalyst speciation and NMR spectroscopic resting state determination. Guided by our mechanistic results, an electron-poor variant of meso -PAd2-DalPhos (i.e., meso -L9 ) was synthesized to promote challenging C(sp 2 )–( O -enolate) reductive elimination furnishing 2-substituted benzofurans, while an electron-rich variant (i.e., meso -L10 ) was employed to prevent competitive C(sp 2 )–( O -enolate) reductive elimination en route to 3-acyl-2-substituted NH-indoles.

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)0.001
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation 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 score0.308
Threshold uncertainty score0.672

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.002
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 science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.013
GPT teacher head0.279
Teacher spread0.266 · 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.

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

Citations2
Published2025
Admission routes2
Has abstractyes

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