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Record W4393380280 · doi:10.1021/jacs.4c01474

(Phenoxyimine)nickel-Catalyzed C(sp<sup>2</sup>)–C(sp<sup>3</sup>) Suzuki–Miyaura Cross-Coupling: Evidence for a Recovering Radical Chain Mechanism

2024· article· en· W4393380280 on OpenAlexfundno aff
L. Reginald Mills, Eric M. Simmons, Heejun Lee, Eva Nester, Junho Kim, Steven R. Wisniewski, Matthew V. Pecoraro, Paul J. Chirik

Bibliographic record

VenueJournal of the American Chemical Society · 2024
Typearticle
Languageen
FieldChemistry
TopicCatalytic Cross-Coupling Reactions
Canadian institutionsnot available
FundersNatural Sciences and Engineering Research Council of CanadaBristol-Myers Squibb Foundation
KeywordsChemistryReductive eliminationArylNickelCatalysisTransmetalationMedicinal chemistryAlkylCatalytic cycleBromideAryl radicalOxidative additionRadicalPhotochemistryOrganic chemistry

Abstract

fetched live from OpenAlex

Phenoxyimine (FI)–nickel(II)(2-tolyl)(DMAP) compounds were synthesized and evaluated as precatalysts for the C(sp 2 )–C(sp 3 ) Suzuki–Miyaura cross coupling of (hetero)arylboronic acids with alkyl bromides. With 5 mol % of the optimal (Me OMe FI)Ni(Aryl)(DMAP) precatalyst, the scope of the cross-coupling reaction was established and included a variety of (hetero)arylboronic acids and alkyl bromides (>50 examples, 33–97% yield). A β-hydride elimination–reductive elimination sequence from reaction with potassium isopropoxide base, yielding a potassium (FI)nickel(0)ate, was identified as a catalyst activation pathway that is responsible for halogen atom abstraction from the alkyl bromide. A combination of NMR and EPR spectroscopies identified (FI)nickel(II)–aryl complexes as the resting state during catalysis with no evidence for long-lived organic radical or odd-electron nickel intermediates. These data establish that the radical chain is short-lived and undergoes facile termination and also support a “recovering radical chain” process whereby the (FI)nickel(II)–aryl compound continually (re)initiates the radical chain. Kinetic studies established that the rate of C(sp 2 )–C(sp 3 ) product formation was proportional to the concentration of the (FI)nickel(II)–aryl resting state that captures the alkyl radical for chain propagation. The proposed mechanism involves two key and concurrently operating catalytic cycles; the first involving a nickel(I/II/III) radical propagation cycle consisting of radical capture at (FI)nickel(II)–aryl, C(sp 2 )–C(sp 3 ) reductive elimination, bromine atom abstraction from C(sp 3 )–Br, and transmetalation; and the second involving an off-cycle catalyst recovery process by slow (FI)nickel(II)–aryl → (FI)nickel(0)ate conversion for nickel(I) regeneration.

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)0.002
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
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 score0.271
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.003
Bibliometrics0.0000.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0020.001
Research integrity0.0000.002
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 head0.031
GPT teacher head0.320
Teacher spread0.289 · 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

Citations11
Published2024
Admission routes1
Has abstractyes

Explore more

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