Copper-Mediated Trifluoromethylation of α‑Diazo Esters with TMSCF₃: The Important Role of Water as a Promoter

Copper-mediated trifluoromethylation of α-diazo esters with TMSCF₃ reagent has been developed as a new method to prepare α-trifluoromethyl esters. This trifluoromethylation reaction represents the first example of fluoroalkylation of a non-fluorinated carbene precursor. Water plays an important role in promoting the reaction by activating the “CuCF₃” species prepared from CuI/TMSCF₃/CsF (1.0:1.1:1.1). The scope of this trifluoro­methyl­ation reaction is broad, and its efficiency is demonstrated in the synthesis of a variety of aryl-, benzyl-, and alkyl-substituted 3,3,3-trifluoro­propano­ates

From Olefination to Alkylation: In-Situ Halogenation of Julia–Kocienski Intermediates Leading to Formal Nucleophilic Iodo- and Bromodifluoromethylation of Carbonyl Compounds

Iodo- and bromodifluoromethylated compounds are important synthetic intermediates and halogen-bond acceptors. However, direct introduction of −CF₂I and −CF₂Br groups through nucleophilic addition is particularly challenging because of the high tendency of decomposition of CF₂Br^– and CF₂I^– to difluorocarbene. In this work, we have developed a formal nucleophilic iodo- and bromodifluoromethylation for carbonyl compounds. The key strategy of the method is the halogenation of in situ-generated sulfinate intermediates from the Julia–Kocienski reaction to change the reaction pathway from the traditional olefination to alkylation. Interesting halogen−π interactions between the halocarbon and aromatic donors were observed in the crystal structures of the products. The method could also be extended to the introduction of other fluorinated groups, such as −CFClBr, −CFClI, −CFBr₂, and −CFMeI, which opens up new avenues for the synthesis of a wide range of useful fluorinated products

Spontaneous Resolution of Julia-Kocienski Intermediates Facilitates Phase Separation to Produce <i>Z</i>- and <i>E</i>‑Monofluoroalkenes

The monofluoroalkene motif is important in drug development as it serves as a peptide bond isostere and is found in a number of biologically active compounds with various pharmacological activities. Direct olefination of carbonyl compound is a straightforward way to prepare monofluoroalkenes; however, these methods often result in a mixture of <i>Z</i>- and <i>E</i>-isomers that cannot be easily separated. We discovered a unique spontaneous resolving reaction that simultaneously addresses the problems in the synthesis and separation of <i>Z</i>- and <i>E</i>-monofluoroalkenes. The reaction is accompanied by a highly efficient spontaneous kinetic resolution and phase labeling of monofluoroalkene precursors which allows the separation of <i>Z</i>- and <i>E</i>-monofluoroalkenes by liquid–liquid extraction. The application of the method is demonstrated by the synthesis and separation of potential anticancer agents, which are inseparable by HPLC

From Olefination to Alkylation: In-Situ Halogenation of Julia–Kocienski Intermediates Leading to Formal Nucleophilic Iodo- and Bromodifluoromethylation of Carbonyl Compounds

Iodo- and bromodifluoromethylated compounds are important synthetic intermediates and halogen-bond acceptors. However, direct introduction of −CF₂I and −CF₂Br groups through nucleophilic addition is particularly challenging because of the high tendency of decomposition of CF₂Br^– and CF₂I^– to difluorocarbene. In this work, we have developed a formal nucleophilic iodo- and bromodifluoromethylation for carbonyl compounds. The key strategy of the method is the halogenation of in situ-generated sulfinate intermediates from the Julia–Kocienski reaction to change the reaction pathway from the traditional olefination to alkylation. Interesting halogen−π interactions between the halocarbon and aromatic donors were observed in the crystal structures of the products. The method could also be extended to the introduction of other fluorinated groups, such as −CFClBr, −CFClI, −CFBr₂, and −CFMeI, which opens up new avenues for the synthesis of a wide range of useful fluorinated products

From Olefination to Alkylation: In-Situ Halogenation of Julia–Kocienski Intermediates Leading to Formal Nucleophilic Iodo- and Bromodifluoromethylation of Carbonyl Compounds

Iodo- and bromodifluoromethylated compounds are important synthetic intermediates and halogen-bond acceptors. However, direct introduction of −CF₂I and −CF₂Br groups through nucleophilic addition is particularly challenging because of the high tendency of decomposition of CF₂Br^– and CF₂I^– to difluorocarbene. In this work, we have developed a formal nucleophilic iodo- and bromodifluoromethylation for carbonyl compounds. The key strategy of the method is the halogenation of in situ-generated sulfinate intermediates from the Julia–Kocienski reaction to change the reaction pathway from the traditional olefination to alkylation. Interesting halogen−π interactions between the halocarbon and aromatic donors were observed in the crystal structures of the products. The method could also be extended to the introduction of other fluorinated groups, such as −CFClBr, −CFClI, −CFBr₂, and −CFMeI, which opens up new avenues for the synthesis of a wide range of useful fluorinated products

Copper-Catalyzed Trifluoromethylation of Polysubstituted Alkenes Assisted by Decarboxylation

An efficient copper-catalyzed trifluoromethylation of polysubstituted alkenes assisted by decarboxylation of β,γ-unsaturated carboxylic acids has been achieved. The reaction provides a general method to construct allylic and vinylic CF₃-substituted compounds under mild conditions

<i>N</i>‑Tosyl‑<i>S</i>‑difluoromethyl‑<i>S</i>‑phenylsulfoximine: A New Difluoromethylation Reagent for S‑, N‑, and C‑Nucleophiles

<i>N</i>‑Tosyl‑<i>S</i>‑difluoromethyl‑<i>S</i>‑phenylsulfoximine: A New Difluoromethylation Reagent for S‑, N‑, and C‑Nucleophile

From Olefination to Alkylation: In-Situ Halogenation of Julia–Kocienski Intermediates Leading to Formal Nucleophilic Iodo- and Bromodifluoromethylation of Carbonyl Compounds

Iodo- and bromodifluoromethylated compounds are important synthetic intermediates and halogen-bond acceptors. However, direct introduction of −CF₂I and −CF₂Br groups through nucleophilic addition is particularly challenging because of the high tendency of decomposition of CF₂Br^– and CF₂I^– to difluorocarbene. In this work, we have developed a formal nucleophilic iodo- and bromodifluoromethylation for carbonyl compounds. The key strategy of the method is the halogenation of in situ-generated sulfinate intermediates from the Julia–Kocienski reaction to change the reaction pathway from the traditional olefination to alkylation. Interesting halogen−π interactions between the halocarbon and aromatic donors were observed in the crystal structures of the products. The method could also be extended to the introduction of other fluorinated groups, such as −CFClBr, −CFClI, −CFBr₂, and −CFMeI, which opens up new avenues for the synthesis of a wide range of useful fluorinated products

Copper-Mediated Fluoroalkylation of Aryl Iodides Enables Facile Access to Diverse Fluorinated Compounds: The Important Role of the (2-Pyridyl)sulfonyl Group

The (2-pyridyl)sulfonyl group was found to be a multifunctional group in the preparation of structurally diverse fluorinated products. It not only facilitates the copper-mediated (or catalyzed) cross-coupling reaction between α-fluoro sulfone 4a and aryl iodides, but also enables further transformations of the coupling products 2

Fluoroalkylative Aryl Migration of Conjugated <i>N</i>‑Arylsulfonylated Amides Using Easily Accessible Sodium Di- and Monofluoroalkanesulfinates

Fluorinated sulfinate salts R_fSO₂Na (R_f = CF₂H, CF₂Ph, and CH₂F) have been prepared via NaBH₄-mediated reduction of the corresponding benzo­[<i>d</i>]­thiazol-2-yl sulfones, and their synthetic application as di- and monofluoroalkyl radical precursors is demonstrated in the silver-catalyzed cascade fluoroalkylation/aryl migration/SO₂ extrusion of conjugated <i>N</i>-arylsulfonylated amides