ArticleNature synthesis2025
Synthesis of chiral difluoromethyl cyclopropanes through desymmetric difluoromethylation of cyclopropenes enabled by enantioselective copper catalysis.
Article in Nature synthesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Rigid polyanion architectures enable multiple ion-transport pathways and nanocluster dynamics in composite polymer battery electrolytes.Nature nanotechnology · 2026Article
- Nickel-Boryl-Catalyzed Modular Alkyl Difluoromethylation Enabled by an NMP-Stabilized ICFAngewandte Chemie (International ed. in English) · 2026Article
- Electrosynthesis of 1,1-Bis(difluoromethyl)alkenes via Twofold C-H Difluoromethylation as Bioisosteres of Elusive 1,1-Enediols.Nature communications · 2026Article
- Enantioselective Reductive Alkenylation of α-CFAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The incorporation of enantioenriched difluoromethyl cyclopropane (DFC) groups into drug candidates has garnered increasing attention in the pharmaceutical industry due to the unique ability of the DFC groups to serve as conformationally rigid hydrogen-bond donors. Despite their potential, the widespread use of chiral DFC groups has been limited by their challenging synthesis. Here we report the use of difluoromethyl-copper complexes for the development of a desymmetric difluoromethylation reaction, using enantioselective copper catalysis. Through desymmetric difluoromethylation of cyclopropenes and subsequent electrophilic functionalization, this method achieves high efficiency and enantioselectivity, enabling the modular construction of chiral DFC moieties. The synthetic utility of this strategy is demonstrated through the synthesis of a variety of chiral DFC-containing compounds, including analogues of pharmacologically relevant molecules. This reactivity of difluoromethyl-copper species opens opportunities for broader application in medicinal chemistry and the development of reactions for the construction of difluoromethyl-containing stereocentres.
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Registered trials
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