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Record W2518655988 · doi:10.1002/chem.201603933

N‐Heteroarylation of Optically Pure α‐Amino Esters using the Pd‐PEPPSI‐IPent<sup>Cl</sup>‐<i>o</i>‐picoline Pre‐Catalyst

2016· article· en· W2518655988 on OpenAlexafffund
Sepideh Sharif, David Mitchell, Michael J. Rodriguez, Jennifer L. Farmer, Michael G. Organ

Bibliographic record

VenueChemistry - A European Journal · 2016
Typearticle
Languageen
FieldChemistry
TopicCatalytic C–H Functionalization Methods
Canadian institutionsUniversity of OttawaYork University
FundersNatural Sciences and Engineering Research Council of CanadaEli Lilly and Company
KeywordsRacemizationChemistryPicolineSteric effectsPyridineCatalysisMedicinal chemistryMoietyPalladiumAmino acidOrganic chemistry

Abstract

fetched live from OpenAlex

Abstract A robust, mild, and efficient method for the Pd‐catalyzed N‐heteroarylation of optically pure α‐amino esters was developed. Dichloro[1,3‐bis(2,6‐di‐3‐pentylphenyl)imidazol‐2‐ylidene]( o ‐picoline)palladium(II) (Pd‐PEPPSI‐IPent Cl ‐ o ‐picoline; PEPPSI=pyridine enhanced pre‐catalyst preparation, stabilization, and initiation) was shown to effectively couple a variety of amino acids as the tert ‐butyl ester with heteroaryl chlorides in high yields and with excellent stereoretention of the acidic proton adjacent to the ester. Control experiments revealed that racemization is base‐mediated, with no evidence of Pd‐mediated β‐hydride elimination when using Pd‐PEPPSI‐IPent Cl , and that racemization occurs only after the product is formed, that is, the non‐arylated starting amino ester does not deprotonate under our reaction conditions. Studies also revealed that increasing the steric bulk of the ester moiety on the amino acid (e.g., ethyl to tert ‐butyl) drastically slows racemization of the product.

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient 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 score0.062
Threshold uncertainty score1.000

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 science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0040.000

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 head0.028
GPT teacher head0.268
Teacher spread0.240 · 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

Citations38
Published2016
Admission routes2
Has abstractyes

Explore more

Same venueChemistry - A European JournalSame topicCatalytic C–H Functionalization MethodsFrench-language works237,207