Synthesis of fluoro-functionalized diaryl-λ3-iodonium salts and their cytotoxicity against human lymphoma U937 cells.

Conscious of the potential bioactivity of fluorine, an investigation was conducted using various fluorine-containing diaryliodonium salts in order to study and compare their biological activity against human lymphoma U937 cells. Most of the compounds tested are well-known reagents for fluoro-functionalized arylation reactions in synthetic organic chemistry, but their biological properties are not fully understood. Herein, after initially investigating 18 fluoro-functionalized reagents, we discovered that the ortho-fluoro-functionalized diaryliodonium salt reagents showed remarkable cytotoxicity in vitro. These results led us to synthesize more compounds, previously unknown sterically demanding diaryliodonium salts having a pentafluorosulfanyl (SF5) functional group at the ortho-position, that is, unsymmetrical ortho-SF5 phenylaryl-λ3-iodonium salts. Newly synthesized mesityl(2-(pentafluoro-λ6-sulfanyl)phenyl)iodonium exhibited the greatest potency in vitro against U937 cells. Evaluation of the cytotoxicity of selected phenylaryl-λ3-iodonium salts against AGLCL (a normal human B cell line) was also examined.

Electrophilic Triflyl-arylation and Triflyl-pyridylation by Unsymmetrical Aryl/Pyridyl-λ3-iodonium Salts: Synthesis of Aryl and Pyridyl Triflones.

Unsymmetrical diaryl-λ3-iodonium salts containing aryl triflone (Ar-SO2CF3) were designed and synthesized. X-ray crystal structure analysis of the salt indicated a T-shaped geometry at the iodine atom. The salts were found to be powerful electrophilic reagents for triflyl-arylation of C-, N-, and O-centered nucleophiles under mild conditions. Electrophilic transfer of pyridine triflone (Py-SO2CF3) to nucleophiles was also realized by the use of corresponding triflylpyridyl-aryl-λ3-iodonium salts. Selection of auxiliaries (dummy ligands) of unsymmetrical diaryl-λ3-iodonium salts is crucial for this transformation.

An eccentric rod-like linear connection of two heterocycles: synthesis of pyridine trans-tetrafluoro-λ6-sulfanyl triazoles.

The trans-tetrafluoro-λ6-sulfane (SF4) group has been utilized as a unique three-dimensional building block for the linear connection of two independent N-heterocycles, pyridines and triazoles. The linearly connected heterocyclic compounds were synthesized by thermal Huisgen 1,3-dipolar cycloaddition between previously unknown pyridine SF4-alkynes and readily available azides, providing a series of rod-like SF4-connected N-heterocycles in good to excellent yields. X-ray crystallographic analysis of the target products revealed the trans-geometry of the SF4 group, which linearly connects two independent N-heterocycles. This research will open the field of chemistry of SF4-connected heterocyclic compounds.

SF5-Pyridylaryl-λ3-iodonium salts and their utility as electrophilic reagents to access SF5-pyridine derivatives in the late-stage of synthesis.

Electrophilic pentafluorosulfanyl (SF5) heteroarylation of target molecules using novel reagents is described. Unsymmetrical diaryliodonium reagents 1 having 2-SF5-pyridine have been synthesized in good yields. They are efficient electrophilic reagents for carbon and heterocentered nucleophiles, producing the corresponding SF5-pyridine derivatives in good to excellent yields.