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, Constantin G. Daniliuc, Ryan Gilmour 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.
para-Selective dearomatization of phenols by I(i)/I(iii) catalysis-based fluorination Timo Stünkel, Kathrin Siebold, Daichi Okumatsu, Kazuki Murata, Louise Ruyet, Constantin G. Daniliuc, Ryan Gilmour Chemical Science, 2023 The regio- and enantio-selective dearomatization of phenols has been achieved by I(i)/I(iii) catalysis enabled fluorination.
Distal Construction of a Carbon-SCF2R Bond on Aliphatic Alcohols Enabled by 1,5-Hydrogen-Atom Transfer Fabien Petit‐Cancelier, Louise Ruyet, Samuel Couve‐Bonnaire, Tatiana Besset Advanced Synthesis and Catalysis, 2022 Abstract An approach for the distal construction of a C( sp 3 )−SCF 2 R bond on aliphatic alcohols enabled by 1,5‐hydrogen‐atom transfer (HAT) was developed. In the presence of a hypervalent iodine (PIDA) and readily available ArSO 2 SCF 2 R reagents, this transition metal‐free approach allowed the remote functionalization of a broad variety of alcohols with emergent and high added‐value SCF 2 R moieties (R=H, F, CO 2 Et and PO(OEt) 2 ) under blue light irradiation. magnified image
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, Thomas Poisson, Zoltán Novák, Tatiana Besset 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.
Transition Metal-Free Regioselective Remote C−H Bond 2,2,2-Trifluoroethoxylation of 8-Aminoquinoline Derivatives at the C5 Position Louise Ruyet, Thomas Poisson, Tatiana Besset European Journal of Organic Chemistry, 2021 Abstract The regioselective 2,2,2‐trifluoroethoxylation at the C5 position of amides derived from the 8‐aminoquinoline has been developed. In the presence of PIDA, an unprecedented and undirected transition metal‐free transformation was achieved using the readily available and appealing 2,2,2‐trifluoroethanol as the fluorinated source. The selective distal 2,2,2‐trifluoroethoxylation of an array of amides was achieved in moderate to good yields (12 examples, up to 61 % yield). This approach provided efficient access to high‐value added fluorinated quinoline derivatives, key building blocks for bulk and fine chemical industry.
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.
