The o-nitro derivative 24 was nevertheless obtained in 13% yield (86% Ar-SF3) under preliminary conditions, while o-fluoro derivative 25 as well as the mixed SF3/SF5 product 45 showed high yields. To identify suitable protecting groups, we tested several phenol-and aniline disulfide derivatives. For phenols, benzyl (Bn, 28) and methoxymethyl (MOM, 29) protections give high yields, while for anilines phthalimides (Phth, 27) and tert-butyloxycarbonyl (Boc, 33) are compatible. When investigating N-heterocyclic thiols, we could obtain SF5-quinoline 37 and several 2-SF5 pyridine derivatives in good to excellent yields. With increasing electrondeficiency we detected an increasing amount of 2-fluorination instead of pentafluorosulfanylation, which we account to a nucleophilic aromatic substitution (SNAr) side reactions. To obtain compounds with multiple SF5 groups, we tested several aryl di-or tri-thiols and obtained the bis-and tris-pentafluorosulfanylated product in good to excellent yields. Bis-SF5 compound 47 is a frequently employed SF5-synthon for the synthesis of SF5-NaBArF, as well as several pentafluorosulfanylated catalysts. To evaluate scalability, we reacted nitro-substituted disulfide 50 on a 4 mmol scale (1.2 g) and obtained SF5-aniline 51 in 84% over two steps in a total of 1.5 h reaction time (Fig. ). 51 is the intermediate for the synthesis of the SF5-lefluamide, which displayed two-fold greater potency than its original, commercialized CF3-version, and the antimalarial drug DSM265 the first SF5-compound in clinical development. In order to connect this reaction to a wider set of building blocks, we next searched for suitable thiophenol derivatives that could be obtained through cross-coupling chemistry while also directly yield ArSF5 compounds in the oxidative fluorination (Fig. ). We identified the thiotrityl (STr) and thiobenzoyl (SBz), as well as thiophthalimide (S-Phth), recently utilized by Cornella and coworkers, as suitable groups converting to SF5 with high efficiency (>95%). Other thiophenol derivatives would either only partially (tertbutyl thioether, up to 41% yield) or not at (allyl or benzyl thioethers) liberate the protecting group, decompose (silicon-containing groups and thioacetate) or give only unsatisfactory yields (thiocyanate, up to 68% yield). Subsequently, a generalized pentafluorosulfanylation approach was completed with the development of cross-coupling methods for the synthesis of thiobenzoates and trityl thioethers (Step 1 in Fig. ). Although precedence exists, the cross-coupling reactions of these thio-moieties were highly underdeveloped. Aryl iodides and diazonium salts could effectively be converted to aryl thiobenzoates through Cu(I) catalysis using (phen)CuSBz (cat 1, pre-formed or generated in situ) in good to excellent yields (see SI for details). For aryl bromides, we identified Pd(II) pre-catalysts [Pd(cinnamyl)(tBuXPhos)]OTf (cat 2) and [Pd(allyl)(AlPhos)]OTf (cat 3) to obtain aryl trityl thioethers in high yields (see SI for details). Nucleophilic aromatic substitution (SNAr) with potassium thiotritylate (KSTr) furthermore opened an avenue for the utilization of electron-deficient aryl fluorides. Our efforts conclude with a greatly expanded access of aryl-and heteroaryl SF5 compounds through the generalized utilization of aryl fluorides, bromides, iodides and diazonium salts (Fig. ). The oxidative fluorination of thiobenzoates and trityl thioethers proceeded smoothly in the presence of a variety of functional groups (26, 52-71) as well as oxygen-or nitrogen-containing heterocycles (57, 59, 65) in good to excellent yields. The double pentafluorosulfanylation of an aryl bis-thiobenzoate toward valuable SF5-synthon 49 proceeded in good yield (70%). With highly electron-rich substrates (one to three OMe groups) we detected decreasing yields for products 26, 69, 70 with increasing electron-density due to side-reactions, pointing to a limitation of the current reaction conditions. For 3-substituted thiolated (SBz or STr) pyridines (60, 67), we observed C-H fluorination in the 2-position in addition to pentafluorosulfanylation.(40) Finally, we utilized our strategy for an improved synthesis of the SF5-liquid crystal 74 from the corresponding aryl bromide 72 in a high yielding two-step reaction sequence. 19 F NMR integration of reaction mixtures with internal standard. †NMR yield from reaction mixture prior to isolation. See supplementary materials for detailed reaction conditions.