Hydroxylation of Aryl Sulfonium Salts for Phenol Synthesis under Mild Reaction Conditions

Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47–95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions.

Recently, the development of alternative electrophiles [40][41][42][43][44][45][46][47] as substitutes for conventional aryl halides in hydroxylative reactions have aroused considerable attention in the field of synthetic organic chemistry (Scheme 1c) [48][49][50].For instance, Cornella et al. have described how pyridinium salts generated in situ from the reaction of aminoheterocycles with pyrylium tetrafluoroborate salts could be converted into their hydroxylated analogue by utilizing acetohydroxamic acid as a hydroxyl source [48].James et al. have demonstrated that nitroarenes could also be effectively transformed into phenols via a denitrative functionalization protocol that employs their previously developed pyrrole-based oxime as hydroxylating agent under transition-metal-free conditions [49].Cheng and Ye have reported that aryl ammonium salts could also efficiently undergo hydroxylation by using benzaldoxime and acetohydroxamic acid as hydroxide surrogates [50].In recent decades, readily accessible and shelf-stable organosulfonium salts have also been proven to be versatile electrophiles for undergoing a broad range of organic transformations .Although the hydroxylation of aryl thianthrenium salts have been accomplished by using water as hydroxide source, the reaction should be conducted under photoredox conditions in the presence of Ir and Cu catalysts [74].In the continuation of our efforts to develop efficient organic transformations with the use of alternative electrophiles [75][76][77][78][79][80][81][82][83][84] under mild reaction conditions, herein we report a hydroxylation of aryl sulfonium salts by using acetohydroxamic acid and oxime as hydroxylative agents, which enabled the efficient assembly of hydroxylated arenes in modest-to-good yields with good functional group compatibility (Scheme 1d).
x FOR PEER REVIEW 2 of 15 denitrative functionalization protocol that employs their previously developed pyrrolebased oxime as hydroxylating agent under transition-metal-free conditions [49].Cheng and Ye have reported that aryl ammonium salts could also efficiently undergo hydroxylation by using benzaldoxime and acetohydroxamic acid as hydroxide surrogates [50].In recent decades, readily accessible and shelf-stable organosulfonium salts have also been proven to be versatile electrophiles for undergoing a broad range of organic transformations .Although the hydroxylation of aryl thianthrenium salts have been accomplished by using water as hydroxide source, the reaction should be conducted under photoredox conditions in the presence of Ir and Cu catalysts [74].In the continuation of our efforts to develop efficient organic transformations with the use of alternative electrophiles [75][76][77][78][79][80][81][82][83][84] under mild reaction conditions, herein we report a hydroxylation of aryl sulfonium salts by using acetohydroxamic acid and oxime as hydroxylative agents, which enabled the efficient assembly of hydroxylated arenes in modest-to-good yields with good functional group compatibility (Scheme 1d).

Results
Initially, we sought to optimize the reaction conditions for the hydroxylation of (4-cyanophenyl)dimethylsulfonium-trifluoromethanesulfonate (1a) by using N-hydroxyacetamide (2a) as a hydroxylating agent [38] in the co-existence of various bases and solvents.Among the different organic bases and inorganic bases surveyed and outlined in Table 1 (entries 1-11), Cs 2 CO 3 emerged as the base of choice (entry 8), leading to the corresponding phenol 3a in 66% NMR yield when the reaction was carried out in DMSO (1 mL) at   C and 100 • C, entries 19-20) also made no significant difference.Gratifyingly, the NMR yield of product 3a could be further improved to 81% by using 2 mL DMSO as solvent (entry 21).In addition, evaluation of other reaction parameters, including the amount of Cs 2 CO 3 (3 equiv.or 7 equiv., entries [22][23], reaction time (12 h or 24 h, entries 24-25), equivalents of N-hydroxyacetamide 2a (2 equiv.or 4 equiv., entries [26][27], and the amount of DMSO (4 mL, entry 28), were performed.However, in most cases, variation of the reaction conditions either led to decreased product yield or produced a comparable result to that of entry 21.In addition, evaluation of other reaction parameters, including the amount of Cs2CO3 (3 equiv.or 7 equiv., entries [22][23], reaction time (12 h or 24 h, entries [24][25], equivalents of N-hydroxyacetamide 2a (2 equiv.or 4 equiv., entries [26][27], and the amount of DMSO (4 mL, entry 28), were performed.However, in most cases, variation of the reaction conditions either led to decreased product yield or produced a comparable result to that of entry 21.Unless otherwise specified, the reactions were conducted at 80 °C for 18 h by employing 1a (0.5 mmol, 1 equiv.),2a (3 equiv.), and base (5 equiv.) in solvent (1 mL).b NMR yield determined by employing 4-methoxyanisole as internal standard.c Isolated yield.
Under the above established reaction conditions, we investigated an array of aryl sulfonium salts for this hydroxylation reaction by utilizing acetohydroxamic acid 2a as the hydroxylating agent.As summarized in            Under the above established reaction conditions, we investigated an array of aryl sulfonium salts for this hydroxylation reaction by utilizing acetohydroxamic acid 2a as the hydroxylating agent.As summarized in Table 2, aryl sulfonium salts 1a-k, containing an electron-withdrawing group in the aryl ring, efficiently took part in the hydroxylation to give the corresponding phenols at moderate-to-high yields.More significantly, important functional groups, including cyano, nitro, sulfonyl, formyl, keto, and ester, could be well compatible with the established conditions, which could be retained for downstream derivatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing a chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative product was obtained, presumably because of its relatively low reactivity as compared with aryl sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, and analogous to a previous report of Fier and Maloney in which the hydroxylation only worked with an electron-poor aryl halide [38], the present reaction also could not be applied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring which bears an electron-donating substituent.chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative p was obtained, presumably because of its relatively low reactivity as compared wi sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In additio analogous to a previous report of Fier and Maloney in which the hydroxylation worked with an electron-poor aryl halide [38], the present reaction also could not plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring bears an electron-donating substituent.chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whic bears an electron-donating substituent.vatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whic bears an electron-donating substituent.vatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whic bears an electron-donating substituent.vatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whic bears an electron-donating substituent.vatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whic bears an electron-donating substituent.vatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whic bears an electron-donating substituent.vatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whic bears an electron-donating substituent.compatible with the established conditions, which could be retained for downstream der vatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whic bears an electron-donating substituent.compatible with the established conditions, which could be retained for downstream der vatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whi bears an electron-donating substituent.compatible with the established conditions, which could be retained for downstream der vatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whic bears an electron-donating substituent.compatible with the established conditions, which could be retained for downstream der vatization.However, when (4-chlorophenyl)dimethylsulfonium triflate containing chloro atom in the phenyl ring was used as a substrate, no desired hydroxylative produ was obtained, presumably because of its relatively low reactivity as compared with ar sulfonium salt bearing an electron-withdrawing group in the phenyl ring.In addition, an analogous to a previous report of Fier and Maloney in which the hydroxylation on worked with an electron-poor aryl halide [38], the present reaction also could not be a plied to less reactive aryl sulfonium salts derived from an electron-rich aryl ring whic bears an electron-donating substituent.In addition to acetohydroxamic acid 2a, we also investigated the hydroxylation of aryl sulfonium salt 1a by employing benzaldoxime [34][35][36][37]39] (1.3 equiv.)as a hydroxylative reagent.In the beginning, we also optimized the reaction conditions.As outlined in Table 3, the reaction of aryl sulfonium salt 1a with benzaldehyde oxime (2b) proceeded smoothly in the presence of Cs 2 CO 3 in DMSO at 80 • C for 4 h to give the hydroxylated product 3a in 58% NMR yield (entry 1).Ensuing screening of reaction solvent (entries 2-7) revealed that DMF served as the more appropriate solvent of the reaction, which slightly improved the reaction efficiency and gave rise to the corresponding product 3a in 67% NMR yield (entry 7).Next, a variety of bases were also examined in the hydroxylating reaction (entries 8-19).However, Cs 2 CO 3 was still the optimal base for the transformation.Pleasingly, by increasing the amount of 2b to 1.5 equivalents, NMR yield of the product could be increased to 74% (entry 20).product 3a in 58% NMR yield (entry 1).Ensuing screening of reaction solvent (entries 2-7) revealed that DMF served as the more appropriate solvent of the reaction, which slightly improved the reaction efficiency and gave rise to the corresponding product 3a in 67% NMR yield (entry 7).Next, a variety of bases were also examined in the hydroxylating reaction (entries 8-19).However, Cs2CO3 was still the optimal base for the transformation.Pleasingly, by increasing the amount of 2b to 1.5 equivalents, NMR yield of the product could be increased to 74% (entry 20).Cs2CO3 DMF 74 c (70) d a Unless otherwise specified, the reactions were conducted at 80 °C for 4 h by employing 1a (0.5 mmol, 1 equiv.),2b (1.3 equiv.), and base (5 equiv.) in solvent (2 mL).b NMR yield determined by employing 4-methoxyanisole as internal standard.c Using 1.5 equiv. of 2b.d Isolated yield.
Apart from benzaldehyde oxime (2b), a variety of oximes 2 were also evaluated as hydroxide surrogates (Table 4).Of the various oximes 2b-g studied, oxime 2g, derived from pyrrole [39], was found to be the most suitable hydroxylating reagent for the reaction, affording the expected product 3a in 89% NMR yield.Apart from benzaldehyde oxime (2b), a variety of oximes 2 were also evaluated as hydroxide surrogates (Table 4).Of the various oximes 2b-g studied, oxime 2g, derived from pyrrole [39], was found to be the most suitable hydroxylating reagent for the reaction, affording the expected product 3a in 89% NMR yield.With the establishment of the optimized reaction conditions, substrate scope of aryl sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agent.As listed in Table 5, a variety of aryl sulfonium salts 1a-k possessing an electron-poor With the establishment of the optimized reaction conditions, substrate scope of aryl sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agent.With the establishment of the optimized reaction conditions, substrate scope of aryl sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agent.With the establishment of the optimized reaction conditions, substrate scope of aryl sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agent.With the establishment of the optimized reaction conditions, substrate scope of aryl sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agent.With the establishment of the optimized reaction conditions, substrate scope of aryl sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agent.With the establishment of the optimized reaction conditions, substrate scope of aryl sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agent.As listed in Table 5, a variety of aryl sulfonium salts 1a-k possessing an electron-poor phenyl ring could be amenable to the reaction, leading to the corresponding hydroxylated arenes in 47-95% yields.Analogously, the reactions proceeded with tolerances to a plethora of important functionalities, such as CN, NO 2 , SO 2 Me, CHO, COR, and COOR.Additionally, aryl sulfonium salts containing electron-donating group in the aryl ring were proven to be inappropriate for the current hydroxylation reaction, which is similar to reports in the literature [38,39,49,50].With the establishment of the optimized reaction conditions, substrate scope sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating As listed in Table 5, a variety of aryl sulfonium salts 1a-k possessing an electron phenyl ring could be amenable to the reaction, leading to the corresponding hydrox arenes in 47-95% yields.Analogously, the reactions proceeded with tolerances to a ora of important functionalities, such as CN, NO2, SO2Me, CHO, COR, and COOR.tionally, aryl sulfonium salts containing electron-donating group in the aryl ring proven to be inappropriate for the current hydroxylation reaction, which is similar ports in the literature [38,39,49,50].With the establishment of the optimized reaction conditions, substrate scope of ar sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agen As listed in Table 5, a variety of aryl sulfonium salts 1a-k possessing an electron-po phenyl ring could be amenable to the reaction, leading to the corresponding hydroxylate arenes in 47-95% yields.Analogously, the reactions proceeded with tolerances to a plet ora of important functionalities, such as CN, NO2, SO2Me, CHO, COR, and COOR.Add tionally, aryl sulfonium salts containing electron-donating group in the aryl ring we proven to be inappropriate for the current hydroxylation reaction, which is similar to r ports in the literature [38,39,49,50].With the establishment of the optimized reaction conditions, substrate scope of ar sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agen As listed in Table 5, a variety of aryl sulfonium salts 1a-k possessing an electron-po phenyl ring could be amenable to the reaction, leading to the corresponding hydroxylate arenes in 47-95% yields.Analogously, the reactions proceeded with tolerances to a plet ora of important functionalities, such as CN, NO2, SO2Me, CHO, COR, and COOR.Add tionally, aryl sulfonium salts containing electron-donating group in the aryl ring we proven to be inappropriate for the current hydroxylation reaction, which is similar to r ports in the literature [38,39,49,50].With the establishment of the optimized reaction conditions, substrate scope of ar sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agen As listed in Table 5, a variety of aryl sulfonium salts 1a-k possessing an electron-po phenyl ring could be amenable to the reaction, leading to the corresponding hydroxylate arenes in 47-95% yields.Analogously, the reactions proceeded with tolerances to a plet ora of important functionalities, such as CN, NO2, SO2Me, CHO, COR, and COOR.Add tionally, aryl sulfonium salts containing electron-donating group in the aryl ring we proven to be inappropriate for the current hydroxylation reaction, which is similar to r ports in the literature [38,39,49,50].With the establishment of the optimized reaction conditions, substrate scope of ar sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agen As listed in Table 5, a variety of aryl sulfonium salts 1a-k possessing an electron-po phenyl ring could be amenable to the reaction, leading to the corresponding hydroxylate arenes in 47-95% yields.Analogously, the reactions proceeded with tolerances to a plet ora of important functionalities, such as CN, NO2, SO2Me, CHO, COR, and COOR.Add tionally, aryl sulfonium salts containing electron-donating group in the aryl ring we proven to be inappropriate for the current hydroxylation reaction, which is similar to r ports in the literature [38,39,49,50].With the establishment of the optimized reaction conditions, substrate scope of ar sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agen As listed in Table 5, a variety of aryl sulfonium salts 1a-k possessing an electron-po phenyl ring could be amenable to the reaction, leading to the corresponding hydroxylate arenes in 47-95% yields.Analogously, the reactions proceeded with tolerances to a plet ora of important functionalities, such as CN, NO2, SO2Me, CHO, COR, and COOR.Add tionally, aryl sulfonium salts containing electron-donating group in the aryl ring we proven to be inappropriate for the current hydroxylation reaction, which is similar to r ports in the literature [38,39,49,50].With the establishment of the optimized reaction conditions, substrate scope of ar sulfonium salts 1 was investigated with the use of oxime 2g as the hydroxylating agen As listed in Table 5, a variety of aryl sulfonium salts 1a-k possessing an electron-po phenyl ring could be amenable to the reaction, leading to the corresponding hydroxylate arenes in 47-95% yields.Analogously, the reactions proceeded with tolerances to a plet ora of important functionalities, such as CN, NO2, SO2Me, CHO, COR, and COOR.Add tionally, aryl sulfonium salts containing electron-donating group in the aryl ring we proven to be inappropriate for the current hydroxylation reaction, which is similar to r ports in the literature [38,39,49,50].Finally, the scalability of the reactions was also investigated.As illustrated in Schem 2, 3 mmol scale reaction of aryl sulfonium salt 1a with both 2a and 2g worked equally we under the optimized reaction conditions, producing the anticipated product 3a in 73% an 75% yields, respectively.Finally, the scalability of the reactions was also investigated.As illustrated in Schem 2, 3 mmol scale reaction of aryl sulfonium salt 1a with both 2a and 2g worked equally we under the optimized reaction conditions, producing the anticipated product 3a in 73% an 75% yields, respectively.Finally, the scalability of the reactions was also investigated.As illustrated in Schem 2, 3 mmol scale reaction of aryl sulfonium salt 1a with both 2a and 2g worked equally we under the optimized reaction conditions, producing the anticipated product 3a in 73% an 75% yields, respectively.Finally, the scalability of the reactions was also investigated.As illustrated in Schem 2, 3 mmol scale reaction of aryl sulfonium salt 1a with both 2a and 2g worked equally we under the optimized reaction conditions, producing the anticipated product 3a in 73% an 75% yields, respectively.Finally, the scalability of the reactions was also investigated.As illustrated in Schem 2, 3 mmol scale reaction of aryl sulfonium salt 1a with both 2a and 2g worked equally we under the optimized reaction conditions, producing the anticipated product 3a in 73% an 75% yields, respectively.Finally, the scalability of the reactions was also investigated.As illustrated in Scheme 2, 3 mmol scale reaction of aryl sulfonium salt 1a with both 2a and 2g worked equally well under the optimized reaction conditions, producing the anticipated product 3a in 73% and 75% yields, respectively.
Finally, the scalability of the reactions was also investigated.As illustrated in Scheme 2, 3 mmol scale reaction of aryl sulfonium salt 1a with both 2a and 2g worked equally well under the optimized reaction conditions, producing the anticipated product 3a in 73% and 75% yields, respectively.Scheme 2. Scale-up synthesis.
Based on previous reports [34,38,50], possible mechanisms for these two hydroxylative reactions have been tentatively proposed.As shown in Figure 1a, for the reaction of aryl sulfonium salt with aldehyde oxime, the reaction possibly proceeds via the nucleophilic substitution of the aldehyde oxime with the sulfonium salt under the action of base to give intermediate A, accompanied by the generation of dimethyl sulfide as a byproduct.Next, a base-mediated deprotonation of intermediate A, followed by fragmentation and subsequent protonation, affords the corresponding phenol as the final product and aryl nitrile as a byproduct.With regard to hydroxylation employing acetohydroxamic acid as hydroxide source (Figure 1b), the reaction presumably occurs through a similar base-facilitated nucleophilic substitution of acetohydroxamic acid with aryl sulfonium salt to produce intermediate B, along with the formation of Me2S as a byproduct.Subsequently, a Lossen rearrangement takes place to yield the desired phenol after acidific workup.Based on previous reports [34,38,50], possible mechanisms for these two hydroxylative reactions have been tentatively proposed.As shown in Figure 1a, for the reaction of aryl sulfonium salt with aldehyde oxime, the reaction possibly proceeds via the nucleophilic substitution of the aldehyde oxime with the sulfonium salt under the action of base to give intermediate A, accompanied by the generation of dimethyl sulfide as a byproduct.Next, a base-mediated deprotonation of intermediate A, followed by fragmentation and subsequent protonation, affords the corresponding phenol as the final product and aryl nitrile as a byproduct.With regard to hydroxylation employing acetohydroxamic acid as hydroxide source (Figure 1b), the reaction presumably occurs through a similar basefacilitated nucleophilic substitution of acetohydroxamic acid with aryl sulfonium salt to produce intermediate B, along with the formation of Me 2 S as a byproduct.Subsequently, a Lossen rearrangement takes place to yield the desired phenol after acidific workup.
x FOR PEER REVIEW 8 of 15

General Information
Unless otherwise specified, the reagents were purchased from commercial suppliers and used without further purification.All reactions were conducted under N2 atmosphere using undistilled solvent.Analytical thin layer chromatography (TLC) was performed using silica gel plate (0.2 mm thickness).Subsequent to elution, plates were visualized using UV radiation (254 nm).Flash chromatography was performed using Merck silica gel (200-300 mesh) for column chromatography with freshly distilled solvents.IR spectra were recorded on an FT-IR spectrophotometer using KBr optics. 1 H and 13 C NMR spectra were recorded in CDCl3 and DMSO-d 6 on Bruker Avance or Jeol 400 MHz spectrometers.The chemical shifts (δ) are reported in ppm and coupling constants (J) in Hz.NMR splitting patterns are designated as singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m), doublet of doublets (dd), doublet of triplets (dt), doublet of quartets (dq), triplet of doublets (td), triplet of triplets (tt), quartet of doublets (qd), doublet of doublet of doublets (ddd), etc. Tetramethylsilane (TMS) served as internal standard for 1 H and 13 C NMR anal-

General Information
Unless otherwise specified, the reagents were purchased from commercial suppliers and used without further purification.All reactions were conducted under N 2 atmosphere using undistilled solvent.Analytical thin layer chromatography (TLC) was performed using silica gel plate (0.2 mm thickness).Subsequent to elution, plates were visualized using UV radiation (254 nm).Flash chromatography was performed using Merck silica gel (200-300 mesh) for column chromatography with freshly distilled solvents.IR spectra were recorded on an FT-IR spectrophotometer using KBr optics. 1 H and 13 C NMR spectra were recorded in CDCl 3 and DMSO-d 6 on Bruker Avance or Jeol 400 MHz spectrometers.The chemical shifts (δ) are reported in ppm and coupling constants (J) in Hz.NMR splitting patterns are designated as singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m), doublet of doublets (dd), doublet of triplets (dt), doublet of quartets (dq), triplet of doublets (td), triplet of triplets (tt), quartet of doublets (qd), doublet of doublet of doublets (ddd), etc. Tetramethylsilane (TMS) served as internal standard for 1 H and 13 C NMR analysis.High resolution mass spectra (HRMS) were obtained via a Waters Q-TOF Premier Spectrometer (ESI source).

General Procedure for the Synthesis of Oximes 2b-g
A 250 mL round-bottom flask was sequentially charged with aryl aldehyde (20.0 mmol, 1 equiv.),MeOH (100 mL), Na 2 CO 3 (2.54g, 24 mmol, 1.2 equiv.), and NH 2 OH•HCl (1.67 g, 24 mmol, 1.2 equiv.).The reaction mixture was then heated to reflux and stirred for 2 h.The reaction was allowed to cool to room temperature and MeOH was removed under reduced pressure.The residue was dissolved in EtOAc (50 mL) and H 2 O (50 mL).The organic phase was separated and the aqueous phase was extracted with EtOAc (50 mL × 2).The organic extracts were combined, washed with brine (50 mL), and dried over Na 2 SO 4 .The extracts were concentrated under reduced pressure to afford the crude product, which was purified via silica gel column chromatography (using EtOAc/petroleum ether + 3% Et 3 N as eluents) to afford the analytically pure oximes 2b-g.Spectral data of the products are in accordance with those previously documented [39].

General Procedure for the Reaction of Aryl Sulfonium Salt with Acetohydroxamic Acid
To an oven-dried Schlenk tube equipped with a magnetic stir bar was sequentially added aryl sulfonium salt 1 (0.5 mmol, 1 equiv.),acetohydroxamic acid 2a (112.6 mg, 1.5 mmol, 3 equiv.),and Cs 2 CO 3 (814.6mg, 2.5 mmol, 5 equiv.).Then, dry DMSO (2 mL) was added into the tube by syringe.The reaction mixture was stirred at 80 • C for 18 h before quenching with aqueous hydrochloric acid (6 mmol, 6 mL, 1 M in water) and extracting with EtOAc (20 mL × 3).The organic layers were combined, washed with brine, and dried over Na 2 SO 4 .The extracts were concentrated under reduced pressure to afford the crude product, which was further purified via silica gel column chromatography (using EtOAc/petroleum ether as eluents) to yield the analytically pure product 3.

General Procedure for the Reaction of Aryl Sulfonium Salt with Oxime
To an oven-dried Schlenk tube equipped with a magnetic stir bar was sequentially added aryl sulfonium salt 1 (0.5 mmol, 1 equiv.),oxime 2g (93.1 mg, 0.75 mmol, 1.5 equiv.), and Cs 2 CO 3 (814.6mg, 2.5 mmol, 5 equiv.).Then dry DMF (2 mL) was added into the tube by syringe.The reaction mixture was stirred at 80 • C for 4 h before quenching with aqueous hydrochloric acid (6 mmol, 6 mL, 1 M in water) and extracting with EtOAc (20 mL × 3).The organic layers were combined, washed with brine, and dried over Na 2 SO 4 .The extracts were concentrated under reduced pressure to afford the crude product, which was further purified through silica gel column chromatography (using EtOAc/petroleum ether as eluents) to yield the analytically pure product 3.

Scale-Up Reaction of Sulfonium Salt 1a with Acetohydroxamic Acid 2a
To an oven-dried Schlenk tube equipped with a magnetic stir bar was sequentially added aryl sulfonium salt 1a (940.0 mg, 3 mmol, 1 equiv.),acetohydroxamic acid 2a (1013.4mg, 9 mmol, 3 equiv.),and Cs 2 CO 3 (7331.4mg, 15 mmol, 5 equiv.).Then dry DMSO (12 mL) was added into the tube by syringe.The reaction mixture was stirred at 80 • C for 18 h before quenching with aqueous hydrochloric acid (36 mmol, 36 mL, 1 M in water) and extracting with EtOAc (80 mL × 3).The organic layers were combined, washed with brine, and dried over Na 2 SO 4 .The extracts were concentrated under reduced pressure to afford the crude product, which was further purified through silica gel column chromatography (using EtOAc/petroleum ether as eluents) to yield the analytically pure product 3a in 73% yield (262.9 mg).

Scale-Up Reaction of Sulfonium Salt 1a with Oxime 2g
To an oven-dried Schlenk tube equipped with a magnetic stir bar was sequentially added aryl sulfonium salt 1a (940.0 mg, 3 mmol, 1 equiv.),oxime 2g (419.0 mg, 4.5 mmol, 1.5 equiv.), and Cs 2 CO 3 (7331.4mg, 15 mmol, 5 equiv.).Then, dry DMSO (12 mL) was added into the tube by syringe.The reaction mixture was stirred at 80 • C for 4 h before quenching with aqueous hydrochloric acid (36 mmol, 36 mL, 1 M in water) and extracting with EtOAc (80 mL × 3).The organic layers were combined, washed with brine, and dried over Na 2 SO 4 .The extracts were concentrated under reduced pressure to afford the crude product, which was further purified through silica gel column chromatography (using EtOAc/petroleum ether as eluents) to yield the analytically pure product 3a in 75% yield (270.1 mg).

Conclusions
In conclusion, the hydroxylation of aryl sulfonium salts by utilizing acetohydroxamic acid and oxime as hydroxylating reagents was developed.The reactions proceeded effectively with the aid of cesium carbonate to afford a series of hydroxylated arenes in moderate-to-high yields with broad functional group compatibility.In addition, the hydroxylation could be subjected to scale-up synthesis, leading to the desired phenol in a good yield.

Table 1 .
Optimization of reaction conditions a .

Table 1 .
Optimization of reaction conditions.a

Table 2 .
Substrate scope of aryl sulfonium salt a .

Table 2 .
Substrate scope of aryl sulfonium salt.a b Isolated yield.

Table 2 .
Substrate scope of aryl sulfonium salt.a b Isolated yield.

Table 2 .
Substrate scope of aryl sulfonium salt.a b Isolated yield.

Table 3 .
Optimization of reaction conditions a .

Table 3 .
Optimization of reaction conditions.a

Table 4 .
Screening of various oximes a .

Table 5 .
Substrate scope of aryl sulfonium salt a .
c Isolated yield.

Table 5 .
Substrate scope of aryl sulfonium salt.a c Isolated yield.

Table 5 .
Substrate scope of aryl sulfonium salt.a c Isolated yield.

Table 5 .
Substrate scope of aryl sulfonium salt.a c Isolated yield.

Table 5 .
Substrate scope of aryl sulfonium salt.a c Isolated yield.

Table 5 .
Substrate scope of aryl sulfonium salt.a c Isolated yield.

Table 5 .
Substrate scope of aryl sulfonium salt.a c Isolated yield.