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Record W4407384129 · doi:10.1002/ange.202420312

Universal Reagent for Mild and Stereospecific Nucleophilic Substitution of Alcohols with Amines

2025· article· en· W4407384129 on OpenAlexafffund
William S. Bechara, Irina K. Sagamanova, Maxime Dauphinais, Sophie Régnier, Scott B. D. Jarvis, André B. Charette

Bibliographic record

VenueAngewandte Chemie · 2025
Typearticle
Languageen
FieldChemistry
TopicChemical Synthesis and Reactions
Canadian institutionsUniversité de MontréalCentre in Green Chemistry and Catalysis
FundersFonds de recherche du Québec – Nature et technologiesNatural Sciences and Engineering Research Council of Canada
KeywordsStereospecificityChemistryNucleophilic substitutionReagentNucleophilic aromatic substitutionNucleophileSubstitution (logic)Combinatorial chemistryOrganic chemistrySubstitution reactionSNiMedicinal chemistryAcid hydrolysisCatalysisHydrolysis

Abstract

fetched live from OpenAlex

Abstract A user‐friendly reagent for mild and general activation of alcohols towards bimolecular nucleophilic substitution (S N 2) leveraging diverse nucleophiles, including primary and secondary amines is reported herein. The new ion‐paired reagent discovery was based upon the putative zwitterionic betaine intermediate of the Mitsunobu reaction and enabled the one‐step conversion of enantioenriched alcohols to valuable chiral C−X bonds (where X=N, C, S, O or halide). The described activating reagent has also been applied to a one‐step methylation reaction using methanol and to an intermolecular amination/intramolecular cyclization sequence that generates heterocycles, such as tetrahydroisoquinolines. This work provides the first evidence by X‐ray crystallography of a protonated betaine as intermediate in the Mitsunobu reaction.

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)0.000
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 score0.040
Threshold uncertainty score0.342

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.020
GPT teacher head0.242
Teacher spread0.222 · 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

Citations0
Published2025
Admission routes2
Has abstractyes

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