Primary Amine-Catalyzed Enantioselective Fluorination of α-Branched Aldehydes with Low Catalyst Loadings

β,β-diaryl-β-silyloxy diamines enable catalytic enantioselective fluorination of α-branched aldehydes with a broad substrate scope, even at low catalyst loadings (>90% ee, 1-3 mol %). Furthermore, as a synthetic application, the enantioselective syntheses of fluorine-containing biologically active pharmaceuticals─such as LY50340, α-fluorinated NSAIDs, and α-fluorinated reparixin─were successfully demonstrated. DFT calculations revealed that cumulative steric repulsions among the phenyl groups of NFSI, the enamine, and the catalyst are critical for achieving high enantioselectivity.

Authors

Institutions

Publication Details

Journal
The Journal of Organic Chemistry
Published
2025-12-11
DOI
https://doi.org/10.1021/acs.joc.5c02738
Primary Topic
Fluorine in Organic Chemistry
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Primary Amine-Catalyzed Enantioselective Fluorination of α-Branched Aldehydes with Low Catalyst Loadings

Satoru Arimitsu, Katsuki Endo, Masahiro Higashi, K. Sugiyama et al.
The Journal of Organic Chemistry
Fluorine in Organic Chemistry
article

Primary Amine-Catalyzed Enantioselective Fluorination of α-Branched Aldehydes with Low Catalyst Loadings

Satoru Arimitsu, Katsuki Endo, Masahiro Higashi, K. Sugiyama, Daiki Tomon, Riko Genka, Sohta Sakahara
article en

Abstract

β,β-diaryl-β-silyloxy diamines enable catalytic enantioselective fluorination of α-branched aldehydes with a broad substrate scope, even at low catalyst loadings (>90% ee, 1-3 mol %). Furthermore, as a synthetic application, the enantioselective syntheses of fluorine-containing biologically active pharmaceuticals─such as LY50340, α-fluorinated NSAIDs, and α-fluorinated reparixin─were successfully demonstrated. DFT calculations revealed that cumulative steric repulsions among the phenyl groups of NFSI, the enamine, and the catalyst are critical for achieving high enantioselectivity.

The Journal of Organic ChemistryVol. 90(51)
Kyoto University (JP), University of the Ryukyus (JP), Kyoto Katsura Hospital (JP), Nagoya University (JP)
Openalex Percentile: Top 67%
Fluorine in Organic Chemistry
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.