Master Degree in Molecular Chemistry, University of Rennes I, 2018
Chemical engineering Degree majoring in Chemistry and biotechnology fro the living, Ecole Nationale supérieure de Chimie de Rennes, 2018
Catalytic Ring Expanding Difluorination: An Enantioselective Platform to Access β,β-Difluorinated Carbocycles Louise Ruyet, Christoph Roblick, Joel Häfliger, Zi‐Xuan Wang, Tobias Jürgen Stoffels, et al. Angewandte Chemie International Edition, 2024 Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute in the arena of fluorinated medium rings where installing the difluoromethylene unit subtly alters the ring conformation by expanding the internal angle (∠C−CF2−C>∠C−CH2−C): this provides a handle to modulate physicochemistry (e.g. pKa). To reconcile this disparity, a highly modular ring expansion has been devised that leverages simple α,β‐unsaturated esters and amides, and processes them to one‐carbon homologated rings with concomitant geminal difluorination (6 to 10 membered rings, up to 95 % yield). This process is a rare example of the formal difluorination of an internal alkene and is enabled by sequential I(III)‐enabled O‐activation. Validation of enantioselective catalysis in the generation of unprecedented medium ring scaffolds is reported (up to 93 : 7 e.r.) together with X‐ray structural analyses and product derivatization.
Integrating I(I)/I(III) catalysis in reaction cascade design enables the synthesis of gem-difluorinated tetralins from cyclobutanols Joel Häfliger, Louise Ruyet, Nico Stübke, Constantin G. Daniliuc, Ryan Gilmour Nature Communications, 2023 Partially saturated, fluorine-containing rings are ubiquitous across the drug discovery spectrum. This capitalises upon the biological significance of the native structure and the physicochemical advantages conferred by fluorination. Motivated by the significance of aryl tetralins in bioactive small molecules, a reaction cascade has been validated to generate novel gem-difluorinated isosteres from 1,3-diaryl cyclobutanols in a single operation. Under the Brønsted acidity of the catalysis conditions, an acid-catalysed unmasking/fluorination sequence generates a homoallylic fluoride in situ. This species serves as the substrate for an I(I)/I(III) cycle and is processed, via a phenonium ion rearrangement, to an (isolable) 1,3,3-trifluoride. A final C(sp3)-F bond activation event, enabled by HFIP, forges the difluorinated tetralin scaffold. The cascade is highly modular, enabling the intermediates to be intercepted: this provides an expansive platform for the generation of structural diversity.
Z -Selective Pd-catalyzed 2,2,2-trifluoroethylation of acrylamides at room temperature Louise Ruyet, Maria I. Lapuh, Vijay S. Koshti, Tamás Földesi, Philippe Jubault, et al. Chemical Communications, 2021 A straightforward methodology for the selective synthesis of high-value added Z-2,2,2-trifluoroethylated acrylamides by Pd-catalyzed C–H bond activation at room temperature.
Remote trifluoromethylthiolation of alcohols under visible light Manuel Barday, Remi Blieck, Louise Ruyet, Tatiana Besset Tetrahedron, 2020 An unprecedented remote and regioselective trifluoromethylthiolation reaction of alcohols was developed. Under mild conditions, a panel of free-alcohols was selectively functionalized with TolSO2SCF3 reagent as the SCF3 source in the presence of hypervalent iodide (PIDA) under blue light irradiation. This approach offered an operationally simple tool for the construction of a challenging C(sp3)-SCF3 bond at the δ-position of an alcohol by C(sp3)-H bond functionalization. Initial mechanistic studies suggested a radical pathway.
Copper-based fluorinated reagents for the synthesis of CF2R-containing molecules (R = F) Louise Ruyet, Tatiana Besset Beilstein Journal of Organic Chemistry, 2020 Over the years, the development of new methodologies for the introduction of various fluorinated motifs has gained a significant interest due to the importance of fluorine-containing molecules in the pharmaceutical and agrochemical industries. In a world eager to eco-friendlier tools, the need for innovative methods has been growing. To address these two challenges, copper-based reagents were developed to introduce CF2H, CF2RF, CF2CH3, CF2PO(OEt)2 and CF2SO2Ph motifs on a broad range of substrates. Copper-based fluorinated reagents have the advantage of being inexpensive and generally in situ generated or prepared in a few steps, which make them convenient to use. In this review, an overview of the recent advances made for the synthesis of fluorinated molecules using copper-based fluorinated reagents will be given.
