Folate-or L-5-methyltetrahydrofolate-modified poly(ethyleneimine) (PEI) functionalized magnetic microgels (MP-PNAAEF or MP-PNAAEM) for targeted delivery to positive folate-receptor [FR(+)] cancer cells have been successfully prepared. Transmission electron microscopy (TEM) shows that the Fe3O4 nanoparticles are well covered with PNAAEF microgels, exhibiting regular spherical structures with few agglomerates. The mean size of the magnetic microgels measured by dynamic light scattering (DLS) is dependent on temperature and pH, and they exhibit good thermosensitivity as well as pH sensitivity. The research on drug loading and the drug release behavior of magnetic microgels shows that the MP-PNAAEF and MP-PNAAEM microgels are capable of loading more doxorubicin hydrochloride (DOX) than MP-PNAAE under appropriate conditions, and in vitro release is faster at pH 4.5 than at pH 7.4, and faster at 45 °C than at 37 °C. In vitro cytotoxicity of these microgels to Hela cells [FR(+)] and L02 cells [FR(−)] were evaluated, and all microgels were nontoxic up to a concentration of 15 μg mL−1 toward Hela cells and 30 μg mL−1 toward L02 cells. Specifically, the cellular uptake of MP-PNAAE, MP-PNAAEF and MP-PNAAEM was observed with both cell lines. FA and MTHF modification on the MP-PNAAE increased the microgel uptake by Hela cells, but not by the L02 cells, as demonstrated by fluorescence microscopy; thus, the MTHF may possess remarkable properties toward Hela cells. Meanwhile, the DOX-loaded MP-PNAAEF and MP-PNAAEM microgels present greater cytotoxicity to Hela cells than free DOX and DOX-loaded MP-PNAAE microgels. The results suggest that MTHF may represent a potential ligand for targeted anticancer drug delivery, and the MP-PNAAEF and MP-PNAAEM magnetic microgels may represent a potential tumor targeting drug carrier.

Bromodifluoromethyl substituted β-diketone 3a–3d, prepared from corresponding ketones and ethyl bromodifluoroactate in the presence of sodium methoxide, reacted with aryl hydrazine derivatives affording bromodifluoromethyl substituted pyrazoles in high regioselectivity. The reaction of 3a–3d with hydroxylamine hydrochloride gave dihydroisoxazoles, which afforded bromodifluoromethyl substituted isoxazoles through dehydration by PPA or concentrated sulfuric acid.Bromodifluoromethyl substituted β-diketones reacted with aryl hydrazine derivatives or hydroxylamine hydrochloride affording corresponding bromodifluoromethyl substituted pyrazoles or dihydroisoxazoles, which proceeded dehydration to give bromodifluoromethyl substituted isoxazoles.

In th presence of zinc and a catalytic amount of cuprous chloride, ethyl 4-bromo-4,4-difluoro-3-oxo-2-(triphenylphosphoranylidene)butanoate 1 reacted with carbonyl compounds to give the gem-difluoromethylenated 2-(triphenylphosphoranylidene)-δ-lactones 4 in moderate to high yields.In the presence of zinc and a catalytic amount of cuprous chloride, ethyl 4-bromo-4,4-difluoro-3-oxo-2-(triphenylphosphoranylidene)butanoate reacted with carbonyl compounds to give the gem-difluoromethylenated 2-(triphenylphosphoranylidene)-δ-lactones in one-pot in moderate to high yields.

The polyfluoroalkyl-lactonization of 5-hexenoic acids with the polyfluoroalkyl iodides initiated by sodium dithionite was carried out in aqueous acetonitrile, providing an efficient method for the synthesis of fluorine-containing δ-valerolactones. Formation of RfCH2CHCH(CH2)2COOH appeared to be unexpected minor product in sulfinatodehalogenation reagents.

β-Alkoxyvinyl bromodifluoromethyl ketones 1a, 1b and 1c were synthesized by the reaction of bromodifluoroacetic anhydride with appropriate vinyl ethers in high yields. The acyclic enone 1a reacted with amines to give the corresponding β-aminovinyl bromodifluoromethyl ketones 2 in good yields. The reaction of 1a with electrophilic reagent ICl yielded α-iodoenone 4. The substitution reaction of the cyclic enones 1b and 1c with thio-nucleophiles gave the corresponding difluoromethylene thioethers 6. The three-component reactions of 2 with primary amines and formaldehyde gave multifunctional 1,2,3,4-tetrahydropyrimidine 3 in moderate yields.β-Alkoxyvinyl bromodifluoromethyl ketones were synthesized by the reaction of bromodifluoroacetic anhydride with appropriate vinyl ether. Some electrophilic and nucleophilic reactions of the enones were studied, especially the SRN1 reactions of the enones with thio-nucleophiles.

Fluoroalkylation of pent-4-en-1-ols with RCF2I initiated by Na2S2O4 was carried out at 5–10 °C in aqueous acetonitrile affording corresponding adducts, which were converted to fluoroalkyl tetrahydrofurans by heating in DMF or acetonitrile, providing a convenient method for the synthesis of fluorine-containing tetrahydrofuran derivatives.Fluoroalky tetrahydrofuran derivatives were obtained by reaction of pent-4-en-1-ols with RCF2I initiated by Na2S2O4 followed by heating in DMF or acetonitrile.

The reaction of fluorine-containing halides and acetamides with conjugated dienoic acids initiated by sodium dithionite gave halide-free 1,4-adducts in 40–80% yields, with the E configuration as the major products.

The reaction of polyfluoroalkyl iodides with alkenes or 4-pentenoic acid promoted by sodium bisulfite or sodium sulfite in DMF aqueous solution was realized. The reaction of alkenes gave corresponding adducts, while γ-lactones were obtained in the case of 4-pentenoic acid in good yields.The reaction of polyfluoroalkyl iodides with alkenes or 4-pentenoic acid promoted by sodium bisulfite or sodium sulfite in DMF aqueous solution gave corresponding adducts and γ-lactones in moderate to good yields.

Diethyl iododifluoromethylphosphonate (1) reacted with 4-pentenoic acids in the presence of Na2S2O4 in aqueous acetonitrile solution at ambient temperature to afford various γ-butyrolactones containing α,α-difluoromethylenyl bisphosphonate moiety in moderate to good yields.γ-Butyrolactones containing α,α-difluoromethylenyl bisphosphonates moiety were obtained by the reaction of diethyl iododifluoromethylphosphonate and 4-pentenoic acids initiated by Na2S2O4.

The free radical additions of fluorine-containing halides to 4-pentenamides initiated by Na2S2O4 were investigated. Both polyfluoroalkyl iodide and ethyl iododifluoroacetate, gave rise to fluorine-containing γ-butyrolactones as the main products while bromides such as ethyl bromodifluoroacetate gave the addition–reduction product. After steric and stereo effects on reaction yields were studied using various substrates, it was concluded that the reactions of 4-pentenamides and polyfluoroalkyl iodides provide one alternative approach to prepare γ-butyrolactones with fluorinated side chains.We described the Na2S2O4 initiated free radical additions of fluoroalkyl halides to 4-pentenamides. For polyfluoroalkyl iodides and ethyl iododifluoroacetate, the reaction afforded fluorine-containing γ-butyrolactones as the main products, while reaction of ethyl bromodifluoroacetate only resulted in the addition-debromination product.

A novel synthesis of α,α-difluoro-γ-butyrolactones was realized by the alkaline hydrolysis of the adducts of ethyl iododifluoroacetate and alkenes. Ethyl iododifluoroacetate reacted with alkenes in the presence of sodium dithionite to give the addition products in 62–78% yields. The products were hydrolyzed in 10% aqueous sodium carbonate solution to give α,α-difluoro-γ-butyrolactones in 93–98% yields.

A convenient synthesis of fluoroalkylated γ-butyrolactones was realized through the reaction of fluoroalkyl iodides with 4-pentenoic acid in the presence of catalytic amounts of tetrakis(triphenylphosphine)palladium and sequential treatment with triethylamine in 79–85% yields.