Halo-perfluoroalkoxylation of gem-difluoroalkenes with short-lived alkali metal perfluoroalkoxides in triglyme.

Alkali metal alkoxides play a pivotal role in nucleophilic alkoxylation reactions, offering pathways for the synthesis of ethers, including the increasingly sought-after trifluoromethyl ethers. However, the synthesis of long-chain perfluoroalkyl ethers remains a substantial challenge in this field. Through the innovative use of triglyme to encapsulate potassium ions, we enhanced the stability of short-lived, longer-chain perfluoroalkoxy anions, thereby facilitating efficient nucleophilic perfluoroalkoxylation reactions. This method provides a new precedent for the halo-perfluoroalkoxylation of gem-difluoroalkenes and offers a versatile tool for the design of perfluoroalkyl ethers, including those containing complex moieties of heterocycles and drug molecules. We also demonstrated the utility of the resulting halo-perfluoroalkoxyl adducts through various chemical transformations to valuable diverse perfluoroalkyl ethers.

Development of Perfluoro Decalin/Fluorinated Polyimide Core-Shell Microparticles via SPG Membrane Emulsification Using Methyl Perfluoropropyl Ether Cosolvent.

Red blood cell-inspired perfluorocarbon-encapsulated core-shell particles have been developed for biomedical applications. Although the use of perfluorodecalin (FDC) is expected for core-shell particles owing to its high oxygen solubility, the low solubility of FDC in any organic solvent, owing to its fluorous properties, prevents its use in core-shell particles. In this study, a new cosolvent system composed of dichloromethane (DCM) and heptafluoropropyl methyl ether (HFPME) was found to dissolve both FDC and fluorinated polyimide (FPI) based on a systematic study using a phase diagram, achieving a homogeneous disperse phase for emulsification composed of oxygen-permeable FPI and oxygen-soluble FDC. Using this novel cosolvent system and Shirasu porous glass (SPG) membrane emulsification, FDC-encapsulated FPI shell microparticles were successfully prepared for the first time. In addition to oxygenation, demonstrated using hypoxia-responsive HeLa cells, the fabricated core-shell microparticles exhibited monodispersity, excellent stability, biocompatibility, and oxygen capacity.

Molecular Iodine as a Catalyst for Alkene Difluorination.

The difluorination reaction of alkenes catalyzed by molecular iodine was revealed for the first time. This difluorination reaction affords a simple and practical experimental method and can be applied to many aliphatic and aromatic alkenes bearing synthetically useful functional groups, such as ester, amide, hydroxy, and aryl groups. Preliminary mechanistic studies of this alkene difluorination suggest the existence of two catalytic cycles: the IF-driven cycle and the catalytic cycle by the IF adduct.

Perfluoroalkoxylation reaction via dual concurrent catalysis.

A catalytic amount of CsI enables dual concurrent activation of poorly reactive perfluoroalkoxide and alkyl halides, especially alkyl chlorides, leading to the formation of diverse perfluoroalkoxylated organic compounds. Installation of perfluoroalkoxy groups by this methodology is cost-effective, circumventing the need for over-stoichiometric cesium or silver salts. This methodology also provides high functional group compatibility and tolerance of sterically hindered substrates.

Iodine-Mediated Fluorination of Alkenes with an HF Reagent: Regioselective Synthesis of 2-Fluoroalkyl Iodides.

Fluorination reaction of alkenes with iodine and HF·pyridine complex (pyr·9HF) was performed under mild conditions in the presence of K2S2O8 or Na2S2O8 as an oxidant. Aliphatic and aromatic alkenes underwent iodofluorination to give the iodofluorinated products with high regioselectivity. The substitution reactions of the iodofluorinated product by nitrogen, sulfur, and oxygen nucleophiles indicated further applications as a building block for synthesis of 2-fluoroalkyl-substituted compounds.

Alkali Metal Fluorides in Fluorinated Alcohols: Fundamental Properties and Applications to Electrochemical Fluorination.

Fundamental properties of alkali metal fluorides (MF, M = Cs, K) dissolved in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) or in 3,3,3-trifluoroethanol (TFE) are investigated, including solubility, conductivity, and viscosity. Solid-state structures of single crystals obtained from CsF/HFIP and CsF/TFE are described for the first time, giving insights into the multiple interactions between fluorinated alcohols and CsF. Applications in electrochemical fluorination reactions are successfully demonstrated.

Synthesis of 4,4-Difluoroalkenes by Coupling of α-Substituted α,α-Difluoromethyl Halides with Allyl Sulfones under Photoredox Catalyzed Conditions.

Photoredox-catalyzed allylation of α-gem-difluorinated organohalides with allyl sulfones proceeded smoothly under visible light irradiation to give 4,4-difluoroalkenes in good yields. In the presence of catalytic Ru(bpy)3Cl2, Hantzsch ester, and diisopropylethylamine, the reaction was complete within 2 h. Using the same methodology, three-component cascade reactions to give 6,6-difluoroalkenes were carried out successfully.

Photoredox-Catalyzed Hydrodifluoroalkylation of Alkenes Using Difluorohaloalkyl Compounds and a Hantzsch Ester.

Photoredox-catalyzed hydrodifluoroalkylation of alkenes proceeded smoothly in the presence of a Hantzsch ester as a hydrogen source under visible light irradiation. The reaction was also applicable to the hydrodifluoroalkylation of alkynes, and a continuous photo flow reaction was also successful.