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
- Satoru Arimitsu (ORCID: https://orcid.org/0000-0003-2235-9113)
- Katsuki Endo
- Masahiro Higashi (ORCID: https://orcid.org/0000-0001-9829-389X)
- K. Sugiyama (ORCID: https://orcid.org/0000-0002-3589-9859)
- Daiki Tomon
- Riko Genka
- Sohta Sakahara
Institutions
- Kyoto University (JP)
- University of the Ryukyus (JP)
- Kyoto Katsura Hospital (JP)
- Nagoya University (JP)
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