Synthesis Strategy of Pentafluorothio Group - Reaction of SF₅(CF₂)ₙ

Product Manager：Nick Wilde

In 2015, researchers including Haufe and Thrasher first achieved the radical transformation of SF₅CF₂CF₂Br. Experimental data showed that when triethylborane was used as a catalyst in n-heptane solvent system, SF₅CF₂CF₂Br (248) could dissociate at room temperature to generate reactive radical intermediates, ultimately converting to SF₅CF₂CF₂H (249) with a conversion efficiency of 63%.

Based on this radical initiation mechanism, researchers further discovered that this brominated compound could undergo radical addition with enol ethers (250) to efficiently construct ketone molecules (251) containing SF₅CF₂CF₂ functional groups. More interestingly, these ketone derivatives could undergo characteristic condensation with 2,4-dinitrophenylhydrazine reagent in acidic ethanol environment to form colored phenylhydrazone compounds(252).

In extended studies, the SF₅CF₂CF₂Br-triethylborane reaction system could successfully react with heterocyclic compounds such as 2,3-dihydrofuran (253a) or tetrahydropyran (253b), as well as cyclic dienes like norbornadiene (255) and cyclooctadiene (257), generating corresponding fluorine-containing substitution products (254a/b) and transannular addition products.

When sodium dithionite was used as initiator for SF₅CF₂CF₂Br in ethanol system at 70°C, selective addition to ordinary alkenes (259) could be achieved to obtain linear alkane derivatives (260).

In dichloromethane solvent, α,β-unsaturated ketones (261) could also efficiently participate in the reaction to generate β-fluorine-substituted products (262).

In 2018, Thrasher and Strauss team made important breakthroughs in fullerene functionalization research. Using o-dichlorobenzene as reaction solvent, they reacted C₆₀ (263) with excess copper powder and 4 equivalents of SF₅CF₂CF₂I at 140°C, successfully preparing the 1,7-paradouble addition product C₆₀(CF₂CF₂SF₅)₂ (264) with specific regioselectivity. The study found that when SF₅CF₂I was used as reactant, due to its thermal instability at 150°C, the expected C₆₀(CF₂SF₅)ₙ derivatives could not be obtained.

In 2016, Haufe and Thrasher team developed a synthesis method for SF₅CF₂ enones. Through the reaction of SF₅CF₂COCl with alkenes in pyridine/dichloromethane system, enone 266 was obtained with 65% yield. This intermediate could be converted to cyclic acetal 267, and then reduced by sodium borohydride to alcohol 268 (88% yield). Further derivatization could obtain mesylate 269 or generate alkene 270 through dehydration (20% yield). The research team found significant difficulties in converting hemiactal to aldehyde, therefore did not further explore this transformation pathway.

In 2022, Haufe and Thrasher team synthesized SF₅CF₂I (273, 54% yield) from difluoro(pentafluorosulfanyl)acetic acid 271 through silver oxide/iodine treatment. This iodide could undergo radical addition with alkenes when initiated by triethylborane, efficiently constructing SF₅CF₂-substituted alkanes 275-277.

Aladdin：https://www.aladdinsci.com