Reactions of difluorocarbene with benzyl and alkylzinc halides leading to fluorinated organozinc species have been described. The generated α-difluorinated organozinc reagents are reasonably stable in solution and can be quenched with external electrophiles (iodine, bromine, proton), affording compounds containing the CF(2) fragment.
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http://dx.doi.org/10.1021/ol400122k | DOI Listing |
Chem Sci
January 2025
Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University Wuhan 430071 China
Replacement of a carbonyl group with fluorinated bioisostere (, CF[double bond, length as m-dash]C) has been adopted as a key tactical strategy in drug design and development, which typically improves potency and modulates lipophilicity while maintaining biological activity. Consequently, new -difluoroalkenation reactions have undoubtedly accelerated this shift, and conceptually innovative practices would be of great benefit to medicinal chemists. Here we describe an expeditous protocol for the direct assembly of furan-substituted -difluoroalkenes PFTB-promoted cross-coupling of ene-yne-ketones and difluorocarbene.
View Article and Find Full Text PDFOrg Lett
December 2024
N. D. Zelinsky Institute of Organic Chemistry, 119991 Moscow, Leninsky prosp. 47, Russian Federation.
Beilstein J Org Chem
November 2024
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany.
We present a mechanochemical synthesis of difluoromethyl enol ethers. Utilizing an in situ generation of difluorocarbenes, ketones are efficiently converted to the target products under solvent-free conditions. The reactions proceed at room temperature and are complete within 90 minutes, demonstrating both efficiency and experimental simplicity.
View Article and Find Full Text PDFJ Org Chem
December 2024
Department of Chemistry & Biochemistry, University of California, Santa Barbara, California 93106, United States.
Environmentally respectful methods for generating and utilizing difluorocarbene (:CF) in the synthesis of a wide array of valuable difluoromethylated compounds are disclosed. In particular, the insertion of the CF moiety into aromatic/heteroaromatic alcohols, thiols, olefins, and alkynes under neat or aqueous micellar catalysis conditions is demonstrated. These methods yield both satisfactory results and significantly lower E-Factors compared to traditional synthetic approaches.
View Article and Find Full Text PDFJ Am Chem Soc
November 2024
State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Weijin Road No. 94, Tianjin 300071, China.
The generation of difluorocarbene from difluoromethane bis(sulfonium ylide) through spin-forbidden excitation under irradiation with 450 nm blue light was reported. The formation of difluorocarbene was confirmed by its reaction with styrene derivatives for the generation of difluorocyclopropanation and insertion into RX-H bonds (X = O, S) for the generation of RXCFH. The spin-forbidden excitation mechanism for the formation of difluorocarbene from difluoromethane bis(sulfonium ylide) was supported by spectroscopic and kinetic studies as well as computational chemistry.
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