Synthesis of (2 <i>S</i> ,4 <i>S</i> )-5,5,5,5′,5′-Pentafluoroleucine and (2 <i>S</i> ,4 <i>R</i> )-5,5,5-Trifluoroleucine via Stereoselective Hydrogenation and Hydrodefluorination
We describe the synthesis of two challenging fluorinated amino acids, (2<i>S</i>,4<i>S</i>)-5,5,5,5',5'-pentafluoroleucine and (2<i>S</i>,4<i>R</i>)-5,5,5-trifluoroleucine. The difficulty in synthesizing stems in part from the presence of two chiral centers. Herein, we report the stereoselective hydrogenation and hydrodefluorination of a pentafluoroisobutenyl chain using a chiral Schiff base Ni(II) complex. Depending on the hydrogen pressure, the reaction favors either the formation of a pentafluorinated or trifluorinated chain. This method provides access to enantiopure novel (2<i>S</i>,4<i>S</i>)-5,5,5,5',5'-pentafluoroleucine and (2<i>S</i>,4<i>R</i>)-5,5,5-trifluoroleucine.
Authors
- Guillaume Naulet
- Guillaume Compain (ORCID: https://orcid.org/0000-0002-9556-1016)
- Gilles Guichard (ORCID: https://orcid.org/0000-0002-2584-7502)
- Brice Kauffmann (ORCID: https://orcid.org/0000-0002-2932-3255)
- Sandeep Mummadi
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université de Bordeaux (FR)
- Inserm (FR)
- Bordeaux Population Health (FR)
- Institut Européen de Chimie et Biologie (FR)
- Institut Polytechnique de Bordeaux (FR)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2025-12-17
- DOI
- https://doi.org/10.1021/acs.joc.5c02700
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.00