This report describes a new method for three-component difluoroalkylation and trifluoromethylthiolation/trifluoromethylselenolation of π-bonds via air-stable SCF and SeCF reagents as free-radical initiators of ethyl iododifluoroacetate. β-Proton elimination can be overcome effectively in this reaction system, and a broad substrate scope, including alkenes and alkynes, makes this approach practical and attractive.
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http://dx.doi.org/10.1039/c7cc09083h | DOI Listing |
Org Lett
January 2025
Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan, Hubei 430074, China.
A Cu(I) photoredox-enabled reaction that selectively incorporates a difluoroalkyl group into -aryl glycine derivatives has been established. Using a bench-stable [PhPCFH]Br salt, the -CFH group could be installed either directly on the α-carbon of the glycine backbone or in a three-component fashion using an alkene as a bridge. A series of glycine derivatives have been evaluated, providing access to diverse unnatural amino esters and dipeptides with a -CHF unit.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Laboratory of Asymmetric Catalysis and Synthesis, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Asymmetric -heterocyclic carbene (NHC) organocatalysis is a cornerstone of synthetic organic chemistry. The emerging concept of single-electron NHC catalysis broadened the scope of C-C bond-forming reactions, facilitating the synthesis of a variety of attractive racemic compounds. However, the development of effective and selective chiral NHC catalysts for asymmetric radical-mediated reactions has been challenging.
View Article and Find Full Text PDFJ Org Chem
September 2024
School of Chemistry and Chemical Engineering, Key Laboratory of Advanced Functional Materials and Devices of Anhui Province, Hefei University of Technology, Hefei 230009, P. R. China.
A three-component defluorinative haloalkylation of alkenes with trifluoromethyl compounds and TBAX (X = Cl, Br) via dual photoredox/copper catalysis is reported. The mild conditions are compatible with a wide array of activated trifluoromethyl aromatics bearing diverse substituents, and various nonactivated terminal and internal alkenes, enabling straightforward access to synthetically valuable γ-gem-difluoroalkyl halides with high efficiency. Mechanistic studies indicate that the [Cu] complexes not only serve as XAT catalysts but also facilitate the SET reduction of trifluoromethyl groups by photocatalysts.
View Article and Find Full Text PDFOrg Lett
July 2024
Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
A calcium-mediated three-component selenylation of -difluoroalkenes using alcohols as nucleophiles and -(phenylseleno)phthalimide as the selenylation agent has been developed for the efficient synthesis of various α,α-difluoroalkyl-β-selenides. This selenylation reaction exhibits broad substrate and functional group tolerance, along with high levels of chemo- and regioselectivity. Additionally, the synthetic utility of the developed transformation in the late-stage functionalization of drug molecules was demonstrated.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2024
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry and Chemical Engineering, Center for Advanced Low-Dimension Materials, Donghua University, Shanghai, 201620, China.
A regioselectivity reversed three-component defluorinative alkylboration of alkenes with trifluoromethyls and bis(pinacolato)diboron via dual photoredox/copper catalysis is reported. The mild conditions are compatible with a wide array of nonactivated trifluoromethyl aromatics bearing electron-donating or electron-neutral substituents, trifluoroacetamides, and various nonactivated terminal and internal alkenes, enabling straightforward access to synthetically valuable γ-gem-difluoroalkyl boronates with high efficiency. Furthermore, this protocol is applicable to alkene-tethered trifluoromethyl aromatics to furnish gem-difluoromethylene-containing cyclic compounds.
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