AgBF4-Mediated Chlorine-Fluorine Exchange Fluorination for the Synthesis of Pentafluorosulfanyl (Hetero)arenes

Abstract

We report a new protocol to form pentafluorosulfanyl (hetero)arenes via chlorine-fluorine exchange of (hetero)aryl tetrafluorosulfanyl chlorides by AgBF4. The method enables access to electron-deficient pentafluorosulfanyl(hetero)arenes, which are targets that are difficult to synthesize. Two advantages of AgBF4 are its ease of handling and stability. This would be a general transformation protocol.

Recent Advances in the Synthesis and Medicinal Chemistry of SF5 and SF4Cl Compounds

“…An alternative method for achieving the conversion of aryl- and heteroaryl-SF 4 Cl derivatives – obtained by treatment of the corresponding disulfides with KF/Cl 2 (excess) in acetonitrile – into SF 5 compounds was also developed by Shibata et al 20 Both SF 5 -aryl and -pyridyl products were prepared in moderate isolated yields by this method, based on the treatment of the corresponding SF 4 Cl substrates with AgBF 4 in DCM at room temperature (Scheme 18 ).…”

“…Scheme 16 Synthesis of SF5 pyridine aryliodonium reagent and SF5 heteroarylation of β-ketoester, pirrole and amine 18 Scheme 17 SF5 heteroarylation of phenols and thiols 18 An alternative method for achieving the conversion of aryl-and heteroaryl-SF4Cl derivatives -obtained by treatment of the corresponding disulfides with KF/Cl2 (excess) in acetonitrileinto SF5-compounds was also developed by Shibata et al 20 Both SF5-aryl and -pyridyl products were prepared in moderate isolated yields by this method, based on the treatment of the corresponding SF4Cl-substrates with AgBF4 in DCM at rt (Scheme 18).…”

“…Scheme 18 SF5-Arylation and heteroarylation of SF4Cl compounds via AgBF4 Cl-F exchange and reaction scope 20 Beier et al reported the direct fluorination of ortho-, meta-and para-substituted aromatic thiols and disulfides using elemental fluorine -reactions were performed in acetonitrile with 10 % F2/N2 mixture at -5 °C (optimised conditions) -which afforded the corresponding substituted SF5-benzenes (Scheme 19). 21 The main limitation of the method is represented by the competitive fluorination of the aromatic ring, so that only electron-deficient aryl sulfides/disulfides efficiently lead to the formation of the desired SF5-aromatics.…”

“…Scheme 17 SF 5 heteroarylation of phenols and thiols 18 An alternative method for achieving the conversion of aryl-and heteroaryl-SF 4 Cl derivatives -obtained by treatment of the corresponding disulfides with KF/Cl 2 (excess) in acetonitrile -into SF 5 compounds was also developed by Shibata et al 20 Both SF 5 -aryl and -pyridyl products were prepared in moderate isolated yields by this method, based on the treatment of the corresponding SF 4 Cl substrates with AgBF 4 in DCM at room temperature (Scheme 18). Beier et al reported the direct fluorination of ortho-, meta-and para-substituted aromatic thiols and disulfides using elemental fluorine -reactions were performed in acetonitrile with 10% F 2 /N 2 mixture at -5 °C (optimized conditions) -which afforded the corresponding substituted SF 5 -benzenes (Scheme 19).…”

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

“…reported the synthesis of aryl‐ and heteroaryl‐S VI pentafluorides using HgO and HF (Scheme 32G) [77] . Very recently, the Cornella and Shibata groups independently showed that AgBF 4 is also a valid source of F for the synthesis or Ar−SF 5 compounds (Scheme 32H) [47, 78] . The authors proposed activation of the Cl atom of (hetero)aryl‐SF 4 Cl by Ag + , and subsequent attack of the fluoride atom of the BF 4 anion to the S center by either a concerted or stepwise mechanism.…”