The palladium-catalyzed difluoroalkylation of aryl boronic acids with bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has been developed. This method provides a facile and useful access to a series of functionalized difluoromethylated arenes (ArCF2 PO(OEt)2 , ArCF2 CO2 Et, and ArCF2 CONR(1) R(2) ) that have important applications in drug discovery and development. Preliminary mechanistic studies reveal that a single electron transfer (SET) pathway may be involved in the catalytic cycle.
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http://dx.doi.org/10.1002/anie.201309535 | DOI Listing |
Angew Chem Int Ed Engl
January 2023
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032, China.
The transition-metal-catalyzed carbonylation reaction is a useful approach for ketone synthesis. However, it is often problematic to use exogenous carbonyl reagents, such as gaseous carbon monoxide. In this manuscript, we report a novel palladium-catalyzed coupling reaction of gem-difluoroalkenes and aryl boronic acids that yields bioactive indane-type ketones with an all-carbon α-quaternary center.
View Article and Find Full Text PDFChem Sci
August 2022
Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences 116023 Dalian Liaoning China
The introduction of fluorine atoms into organic molecules is an attractive but challenging topic. In this work, an interesting palladium-catalyzed difluoroalkylative carbonylation of aryl olefins has been developed. A wide range of aryl olefins were transformed into the corresponding difluoropentanedioate compounds with good functional-group tolerance and excellent regioselectivity.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
June 2022
Department of Nanopharmaceutical Sciences & Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya, 466-8555, Japan.
gem-Difluoromethylene moieties are attractive in medicinal chemistry due to their ability to mimic other more ubiquitous functional groups. Thus, effective asymmetric methods for their construction are highly desirable, especially for the industrial production of chiral drugs. Using a Pd-catalyzed asymmetric [4+2] cycloaddition between substituted-2-alkylidenetrimethylene carbonates and gem-difluoroalkyl ketones, we were able to easily access chiral 1,3-dioxanes that contain a tetrasubstituted difluoroalkyl stereogenic center in cyclic and acyclic skeletons.
View Article and Find Full Text PDFOrg Lett
December 2021
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China.
A palladium catalyzed carbonylative cross-coupling of difluoroalkyl halides with alkyl-9-BBN under 1 atm of CO has been developed. The reaction shows broad substrate scope and high functional group tolerance, even toward complex pharmaceuticals, providing a general and straightforward method to access alkyldifluoroalkyl ketones. Preliminary mechanistic studies reveal that a radical pathway is involved in the reaction.
View Article and Find Full Text PDFJ Org Chem
August 2021
School of Public Health, Xinxiang Medical University, Xinxiang 453003, China.
A Pd-catalyzed difluoroalkylation/cyclization/phosphinoylation of 2-vinyloxy arylalkynes with ethyl difluoroiodoacetate and diarylphosphine oxides has been successfully developed. This reaction allows the formation of C-CF, C-C, and C-P(O) bonds in one step, providing a straightforward route to difluoroalkyl-containing tetrasubstituted alkenylphosphine oxides with complete stereoselectivities under mild conditions.
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