Importance of a Fluorine Substituent for the Preparation of meta‐ and para‐Pentafluoro‐λ⁶‐sulfanyl‐Substituted Pyridines

Abstract

Although there are ways to synthesizeo rtho-pentafluoro-l 6 -sulfanyl (SF 5 )p yridines,m eta-and para-SF 5 -substituted pyridines are rare.W edisclose herein ageneral route for their synthesis.The fundamental synthetic approach is the same as reported methods for ortho-SF 5 -substituted pyridines and SF 5 -substituted arenes,that is,oxidative chlorotetrafluorination of the corresponding disulfides to give pyridylsulfur chlorotetrafluorides (SF 4 Cl-pyridines), followed by chloride/fluoride exchange with fluorides.H owever,t he trick in this case is the presence on the pyridine ring of at least one fluorine atom, which is essential for the successful transformation of the disulfides into m-and p-SF 5 -pyridines.A fter enabling the synthesis of an SF 5 -substituted pyridine,o rtho-F groups can be efficiently substituted by C, N, S, and Onucleophiles through an S N Ar pathway.T his methodology provides access to av ariety of previously unavailable SF 5 -substituted pyridine building blocks.

Difluoromethyl 2-Pyridyl Sulfoximine: A Stereoselective Nucleophilic Reagent for Difluoro(aminosulfinyl)methylation and Difluoro(aminosulfonyl)methylation

“…With the isolated major diastereomer of 5l as a model compound, the desired (R)-hydroxyl difluorinated sulfinamide was obtained in 85% yield with excellent stereoselectivity when sodium ethanethiolate/ethanethiol was applied in DMF solution (Figure 4a; for details, see Table 1 in Supporting Information). [52][53][54][55][56] It is worth noting that phenyl sulfoximine 7 failed to undergo Ph-S bond cleavage under the same conditions, indicating the necessity of the 2-pyridyl group in this transformation.…”

Studies of Halogen Bonding Induced by Pentafluorosulfanyl Aryl Iodides: A Potential Group of Halogen Bond Donors in a Rational Drug Design

“…[36][37][38][39][40][41] More and more examples of biologically active SF5-contaning drug candidates have been reported in recent years ( Figure 1c). [34,[37][38][39][40][41] Extending our research to the design and synthesis of SF5-containing biologically attractive molecules [42][43][44][45][46][47][48][49][50][51][52][53][54] and a halogen bonding research program, [55,56] we are interested in aryl iodides 1a-d consisting of SF5-group(s) in the benzene ring as potential drug fragments capable of halogen bonding, in particular, 3,5-bis-pentafluorosulfanyl iodobenzene 1d (Figure 1d).…”