(Hetero)aryl-SVI Fluorides: Synthetic Development and Opportunities

Abstract

(Hetero)arylsulfur compounds where the S atom is in the oxidation state VI represent a large percentage of the molecular functionalities present in organic chemistry. More specifically, (hetero)aryl-S^VI fluorides have recently received enormous attention because of their potential as chemical biology probes, as a result of their reactivity in a simple, modular, and efficient manner. Whereas the synthesis and application of the level 1 fluorination at S^VI atoms (sulfonyl and sulfonimidoyl fluorides) have been widely studied and reviewed, the synthetic strategies towards higher levels of fluorination (levels 2 to 5) are somewhat more limited. This Minireview evaluates and summarizes the progress in the synthesis of highly fluorinated aryl-S^VI compounds at all levels, discussing synthetic strategies, reactivity, the advantages and disadvantages of the synthetic procedures, the proposed mechanisms, and the potential upcoming opportunities.

Keywords: Fluorine; Pentafluorosulfanyl Arenes; Sulfinyl Trifluorides; Sulfur; Tetrafluorosulfanyl Chlorides.

Figure 1

Fluorinated arylsulfur(VI) compounds.

Scheme 1

Use of sulfur(VI) fluoride (SOF₄) gas as a SuFEx reagent.

Scheme 2

Synthesis of ArSNF₂ by Clifford et al.

Scheme 3

Synthesis and reactivity studies of Ar₂SOF₂ by Ruppert.

Scheme 4

Synthesis of cis‐ and trans‐difluoropersulfuranes by Michalak and Martin.[ ¹⁹ , ²⁰ ]

Scheme 5

Synthesis of α‐fluorosulfones via aryl‐alkyl‐sulfur(VI) difluoride.

Scheme 6

XeF₂/Cl⁻ system: synthesis of Ar₂SOF₂ reported by Janzen and Ou.[ ²² , ²³ ]

Scheme 7

Synthesis and application of diarylfluorosulfoxonium cations by Stephan and co‐workers.

Scheme 8

Application of diarylfluorosulfoxonium cation 25 in annulation reactions by Panossian and co‐workers.

Scheme 9

Pioneering syntheses of sulfur(VI) trifluorides.

Scheme 10

Synthesis of aryl‐S^VI oxytrifluorides by Ruppert.

Scheme 11

Synthetic procedure for ArSOF₃ developed by Wang and Cornella.

Scheme 12

Applications of Ar−SF₄Cl in organic synthesis.

Scheme 13

Early examples of perfluoroalkyltetrafluorosulfanes.

Scheme 14

Early examples of alkyl‐ and aryltetrafluorosulfanes by Denney et al.

Scheme 15

Synthesis of Ar−SF₄Cl by Janzen and co‐workers.

Scheme 16

Synthesis of cis‐ and trans‐diaryltetrafluorosulfane mixture reported by Kirsch et al.

Scheme 17

Synthesis of trans‐Ar−SF₄Cl by Umemoto et al.

Scheme 18

Synthesis of 2‐pyridyl‐SF₄Cl by Kanishchev and Dolbier.

Scheme 19

Effect of a fluorine substituent on the synthesis of pyridyl‐SF₄Cl.

Scheme 20

Synthesis of aryl‐ and heteroaryl‐SF₄Cl developed by Pitts, Togni, Santschi et al..

Scheme 21

Synthesis of aryl‐ and heteroaryl‐SF₄Cl from aryl halides developed by Wang and Cornella.

Scheme 22

Synthesis of aryl‐ and (hetero)aryl‐SF₄Cl developed by Shibata and co‐workers.

Scheme 23

Synthesis of aryl‐SF₄Cl from arylphosphorothiolates developed by Wang and Cornella.

Scheme 24

Application of Ar−SF₄Cl in the synthesis of alkyl‐ and alkenyltetrafluoro‐λ⁶‐sulfanes and their derivatization.

Scheme 25

Pioneering syntheses of C−SF₅ and SF₅Cl.

Scheme 26

Early syntheses of Ar−SF₅: synthesis and study of the physical and chemical properties by Sheppard.[ ⁶⁸ , ⁶⁹ ]

Scheme 27

Other preliminary synthetic methods for the synthesis of Ar−SF₅.

Scheme 28

First examples of the synthesis of Ar−SF₅ by direct oxidation using F₂.

Scheme 29

Synthesis of Ar−SF₅ by direct oxidation using XeF₂‐Et₄NCl. ^[23b]

Scheme 30

Synthesis of Ar−SF₅ by direct oxidation using F₂, as developed by Beier and co‐workers.

Scheme 31

First synthesis of Ar−SF₅ from Ar−SF₄Cl by Umemoto et al.

Scheme 32

Conversion of Ar−SF₄Cl into Ar−SF₅: state‐of‐the‐art.

Scheme 33

Synthesis of Ar−SF₅ developed by Hoover and Coffmann.

Scheme 34

Synthesis of Ar−SF₅ developed by Sergeeva and Dolbier.

Scheme 35

Synthesis of different aryl‐SF₅ and heteroaryl‐SF₅ compounds.