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Exploring the Synthetic Utility of Divinyl Ketones

2010· dissertation· en· W23352346 on OpenAlexfundno aff
Andrew C. Silvanus

Bibliographic record

VenueNuclear Medicine and Biology · 2010
Typedissertation
Languageen
FieldChemistry
TopicAsymmetric Synthesis and Catalysis
Canadian institutionsnot available
FundersCanadian Institutes of Health Research
KeywordsIndole testAlkylationChemistryAnnulationTandemRegioselectivityBrønsted–Lowry acid–base theoryEnantiomerCombinatorial chemistryOrganic chemistryStereochemistryCatalysisMaterials science

Abstract

fetched live from OpenAlex

Divided into three distinct research areas, this thesis investigates the synthetic utility of divinyl ketones as versatile substrates in the construction of novel cyclic structures. The first volume of work (Chapter 2) examines the one-pot Brønsted acid-catalysed tandem double alkylation of indole with non-symmetrical divinyl ketones. The [6,5,7] tricyclic indole products are often furnished in excellent yield, with complete regioselectivity and high levels of syn-diastereoselectivity. Optimisation, a thorough substrate investigation and initial results are all discussed within. An in-depth mechanistic study is described in Chapter 3. Experimental and computational data is utilised to elucidate the reaction pathway and help explain the high levels of regioand diastereoselectivity observed during the tandem double alkylation of indoles developed in Chapter 2. The mechanism for the annulation step is shown to proceed via a 7-endo-mode C-2 Friedel-Crafts alkylation of the indole for which the rate-determining step is believed to be the loss of C-2 the proton to regain aromaticity. The final chapter concerns the phase transfer catalysed double Michael addition of activated methylene pronucleophiles to non-symmetrical divinyl ketones. The resultant substituted cyclohexanones are constructed in high yields with broad tolerance to substrate scope. In addition, proof-of-concept levels of enantioselectivity have been obtained with the use of N-alkylated Cinchona alkaloids as chiral phase transfer catalysts. With 36% enantiomeric excess, this tandem [5C+1C] annulation is shown to be an appropriate method of furnishing enantioenriched cyclohexanones.

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)0.001
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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.084
GPT teacher head0.289
Teacher spread0.205 · 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
Published2010
Admission routes1
Has abstractyes

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