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

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-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

AgF-Mediated Fluorinative Homocoupling of <i>gem</i>-Difluoroalkenes

A novel silver­(I)-fluoride-mediated homocoupling reaction of β,β-difluoro­styrene derivatives is described. The transformation is initiated via nucleophilic addition of silver­(I) fluoride to β,β-difluoro­styrenes, which is followed by dimerization of the corresponding benzyl­silver intermediates. The reaction shows good substrate scope, functional group tolerance, and represents the first report on the reactivity of (α-tri­fluoro­methyl)­benzyl­silver species

AgF-Mediated Fluorinative Homocoupling of <i>gem</i>-Difluoroalkenes

A novel silver­(I)-fluoride-mediated homocoupling reaction of β,β-difluoro­styrene derivatives is described. The transformation is initiated via nucleophilic addition of silver­(I) fluoride to β,β-difluoro­styrenes, which is followed by dimerization of the corresponding benzyl­silver intermediates. The reaction shows good substrate scope, functional group tolerance, and represents the first report on the reactivity of (α-tri­fluoro­methyl)­benzyl­silver species

AgF-Mediated Fluorinative Homocoupling of <i>gem</i>-Difluoroalkenes

A novel silver­(I)-fluoride-mediated homocoupling reaction of β,β-difluoro­styrene derivatives is described. The transformation is initiated via nucleophilic addition of silver­(I) fluoride to β,β-difluoro­styrenes, which is followed by dimerization of the corresponding benzyl­silver intermediates. The reaction shows good substrate scope, functional group tolerance, and represents the first report on the reactivity of (α-tri­fluoro­methyl)­benzyl­silver species

Palladium-Catalyzed Monofluoromethylation of Arylboronic Esters with Fluoromethyl Iodide

The first palladium-catalyzed direct monofluoromethylation of arylboronic esters to produce monofluoromethyl arenes is reported. The reaction is typically carried out at room temperature within 4 h and has a good functional group tolerance. The monofluoromethylating agent, CH₂FI, was readily prepared via a halogen-exchange process

Iron-Catalyzed Difluoromethylation of Arylzincs with Difluoromethyl 2‑Pyridyl Sulfone

We report the first iron-catalyzed difluoromethylation of arylzincs with difluoromethyl 2-pyridyl sulfone via selective C–S bond cleavage. This method employs the readily available, bench-stable fluoroalkyl sulfone reagent and inexpensive iron catalyst, allowing facile access to structurally diverse difluoromethylated arenes at low temperatures. The experiment employing a radical clock indicates the involvement of radical species in this iron-catalyzed difluoromethylation process