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Record W4411467026 · doi:10.1021/acs.joc.5c01094

Migrative Reductive Amination of Ketones Enabled by Multitasking Reagents

2025· article· en· W4411467026 on OpenAlexafffund
Artem Khegay, Dennis G. Hall

Bibliographic record

VenueThe Journal of Organic Chemistry · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicChemical Synthesis and Analysis
Canadian institutionsCentennial CollegeUniversity of Alberta
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsReductive aminationReagentChemistryAminationCombinatorial chemistryOrganic chemistryNatural productSolventOrganic synthesisCatalysis

Abstract

fetched live from OpenAlex

Secondary amines are key synthetic intermediates and constituents of pharmaceutical agents. They are often prepared by the classical reductive amination of ketones and aldehydes, a staple reaction in organic chemistry. Reductive amination forms products without modifying the carbon framework, which restricts its power and breadth. To expand chemical space and access isomeric amines with a rearranged skeleton, a migrative variant was developed by orchestrating three distinct reactions in a single flask, without solvent changes, using two inexpensive and nontoxic reagents: a Zn(II) salt and a hydrosilane. Mechanistic insights confirmed that both reagents are uniquely multitasking ─ active and synergistic ─ across all reaction stages, lending a practical open-flask procedure that embodies many ideals of green chemistry. This method demonstrates a wide scope of acyclic and cyclic ketones and aldehydes with both aliphatic and aromatic groups, including bioactive molecules and macrocyclic natural products isolated with highly favorable E-factor, process mass intensity, and other established greenness metrics. Furthermore, the efficiency of this migrative reductive amination was highlighted in a one-step synthesis of the marine natural product haliclorensin C from l-muscone.

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 score0.001
Threshold uncertainty score0.004

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 science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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 head0.003
GPT teacher head0.229
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

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

Citations1
Published2025
Admission routes2
Has abstractyes

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