Synthesis of Aryl Triflones through the Trifluoromethanesulfonylation of Benzynes

Abstract

The direct synthesis of aryl triflones, that is, trifluoromethanesulfonyl arenes, was achieved through the trifluoromethanesulfonylation of benzynes. The trifluoromethanesulfonyl group, one of the fluorinated functional groups, is a highly electron‐negative and mild lipophilic substituent. Aryl triflones have high potential in the synthesis of bioactive compounds and specialty materials. The treatment of 2‐(trimethylsilyl)aryl trifluoromethanesulfonates with cesium fluoride in the presence of 15‐crown‐5 generated benzynes, which reacted with sodium trifluoromethanesulfinate followed by protonation with tBuOH under heating conditions, provided aryl triflones in moderated to good yields. Both symmetrical and unsymmetrical triflones were nicely accessed under the same reaction conditions. Interestingly, the trifluoromethanesulfonylation of unsymmetrical benzyne precursors proceeded smoothly to furnish corresponding aryl triflones in good yields with good to high regioselectivities. The balance of polarization of electric charge as well as steric hindrance of the benzyne intermediates are central factors to control the outcome of regioselectivity.

1. Introduction

Fluorinated aromatics are prevalent in specialty materials, pharmaceuticals, and agrochemicals.1 Aryl fluorides (Ar−F) and benzotrifluorides (Ar−CF₃) have served as two major contributors in the last half century. In recent years, arenes with heteroatom‐linked trifluoromethyl modifications, such as trifluoromethoxy arenes (Ar−OCF₃),2 trifluoromethylthio arenes (Ar−SCF₃),3 and trifluoromethanesulfonyl arenes (aryl triflones, Ar−SO₂CF₃)3d, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 have been considerably targeted. Our group is interested in aryl triflones.3d, 5 Aryl triflones have a functional group, trifluoromethanesulfonyl (SO₂CF₃), which is a stronger electron‐withdrawing group than trifluoromethyl (CF₃) (SO₂CF₃, σ _m=0.79, σ _p=0.93; CF₃, σ _m=0.43, σ _p=0.54), whereas its lipophilicity is milder than that of CF₃ (SO₂CF₃, π=0.55; CF₃, π=0.88).3d, 17 Thus, the replacement of CF₃–arene moieties in existing biologically active molecules and functional materials with CF₃SO₂–arenes is a potential strategy to improve and/or alter the stability and log P values of the original compounds. In fact, aryl triflones have been successfully used as central structural motifs in biologically active molecules,6 functional materials,7 and chiral catalysts.8 The synthesis of aryl triflones has been explored over the last two decades, leading to its categorization into three methodologies: trifluoromethanesulfonylation of arenes,5a, 9 oxidation of aryl trifluoromethyl sulfides,10 and trifluoromethylation of aryl sulfonyl fluorides or aryl sulfonates.11 From the viewpoint of late‐stage functionalization in pharmaceuticals, the direct trifluoromethanesulfonylation of arenes is particularly attractive.12 In this context, we envisaged the use of benzynes for the direct synthesis of aryl triflones. Benzynes have a strained triple bond, which is highly reactive towards a wide variety of addition reactions.18 We, thus, started the investigation of the preparation of aryl triflones using benzynes. During our investigation,13 the only example of the synthesis of trifluoromethanesulfonyl benzene from benzyne was reported (Scheme 1 a).14 However, it focused exclusively on the phenylsulfonylation of benzynes, and thus a general preparation of aryl triflones has not yet been established. Later, Li and co‐workers15 and Zhao et al.,16 in this order, reported the synthesis of aryl triflones from benzynes (Schemes 1 b and 1 c), but their methods were limited to the preparation of ortho‐substituted triflones. Finally, the direct mono‐functionalization of benzynes to triflones continues to have limitations except for the single example by Singh and co‐workers.14 Herein, we disclose a full account of our work for the synthesis of aryl triflones through the trifluoromethanesulfonylation of benzynes (Scheme 1 d).13

Scheme 1.

Synthesis of aryl triflones from benzynes: a) by Singh and co‐workers;14 b) by Li and co‐workers;15 c) by Xu and co‐workers;16 d) this work.

A wide variety of aryl triflones can be nicely accessed in moderated to good yields through the reaction of sodium trifluoromethanesulfinate (NaSO₂CF₃; Langlois reagent)19 with benzynes followed by the addition of tBuOH for protonation. Highly reactive benzyne derivatives were generated in situ from 2‐(trimethylsilyl)aryl trifluoromethanesulfonates with cesium fluoride in the presence of 15‐crown‐5. This method is useful not only for the synthesis of symmetrical aryl triflones, but also unsymmetrical aryl triflones. More importantly, regioselective trifluoromethanesulfonylation of unsymmetrical benzyne precursors was also achieved, depending on both the steric hindrance and polarization of electric charge of benzynes. An ionic pathway, rather than a radical pathway, for the introduction of the SO₂CF₃ moiety to reactive benzynes was suggested by the use of TEMPO (2,2,6,6‐tetramethylpiperidine 1‐oxyl) experiments. The regioselectivity observed was analyzed based on the computations.

2. Results and Discussion

We first investigated the trifluoromethanesulfonylation of benzynes by using 2‐(trimethylsilyl)naphthalen‐3‐yl trifluoromethanesulfonate (1 a) as a benzyne precursor. Under conventional conditions14, 18 with KSO₂CF₃ (2.0 equiv)20 and KF (4.0 equiv) in tetrahydrofuran (THF) at room temperature, no desired trifluoromethanesulfonylated product 2 a was observed (Table 1, entry 1). We next attempted the reaction by using NaSO₂CF₃ and CsF in MeCN at room temperature. Desired 2 a 5g, 11f was obtained in a low yield of 15 % (entry 2). Screening the fluorides did not improve this transformation (entries 3–5), whereas the addition of 15‐crown‐5 increased the yield slightly to 19 % (entry 6). The amount of CsF affected the conversion to 2 a, increasing the yield to 44 % (entry 7). Heating the reaction shortened the reaction time without affecting significantly the yield (entries 8, 9). We further examined the proton source. The use of H₂O was not effective (entry 10), but the addition of 1.0 equivalent of tBuOH improved the yield to 50 % (entry 11). The reaction was not inhibited in the presence of TEMPO, thus an ionic reaction was suggested (entry 12). We also attempted the reaction using sodium methanesulfinate (NaSO₂CH₃) instead of NaSO₂CF₃, but no desired SO₂CH₃‐containing product, 2‐methanesulfonyl naphthalene, was obtained (entry 13). The structure of product 2 a was confirmed by spectroscopic analysis [¹⁹F NMR δ: −78.69 ppm (triflone, SO₂CF₃)] and also by a comparison with an authentic sample of 2 a, which was prepared by the oxidation of 2‐trifluoromethylthio‐naphthalene (see the Supporting Information).

Table 1.

Optimization of reaction conditions.^[a]

Entry	F source [equiv]	Additive	Temp. [°C]	Time [h]	Yield [%]
1[b]	KF (4.0)	18‐crown‐6	RT	24	NR
2	CsF (4.0)	‐	RT	24	15
3	TMAF (4.0)	‐	RT	24	9
4	TBAF⋅3 H2O (4.0)	‐	RT	24	trace
5	TBAT(4.0)	‐	RT	24	trace
6	CsF (4.0)	15‐crown‐5	RT	24	19
7	CsF (6.0)	15‐crown‐5	RT	24	44
8	CsF (6.0)	15‐crown‐5	40	4	45
9	CsF (6.0)	15‐crown‐5	50	4	42
10[c]	CsF (6.0)	15‐crown‐5	40	3	42
11[d]	CsF (6.0)	15‐crown‐5	40	3	50
12[e]	CsF (6.0)	15‐crown‐5	40	3	49
13[f]	CsF (6.0)	15‐crown‐5	40	3	NR[g]

[a] Reaction was carried out with 1 a, NaSO₂CF₃ (2.0 equiv), an F source, and an additive (2.0 equiv) in MeCN (1.0 mL). [b] KSO₂CF₃ was used instead of NaSO₂CF_3, 18‐crown‐6 (6.0 equiv), with THF as the solvent. [c] H₂O (1.0 equiv) was added. [d] tBuOH (1.0 equiv) was added. [e] TEMPO (2.0 equiv) was added. [f] Reaction was carried out using NaSO₂CH₃ instead of NaSO₂CF₃. [g] No desired product, 2‐methanesulfonyl naphthalene, was obtained.

With the optimal reaction conditions in hand, we examined the substrate scope for the trifluoromethanesulfonylation of symmetrical benzynes derived from corresponding precursors, 2‐(trimethylsilyl)phenyl trifluoromethanesulfonate derivatives 1 a–e (Table 2). The simple benzyne generated from 1 b provided the trifluoromethanesulfonyl benzene (2 b) in a moderate yield of 43 % (entry 2). The alkyl‐substituted benzyne derived from 4,5‐dimethyl‐substituted 1 c gave 2 c in 63 % yield. It should be noted that the sterically demanding 3,6‐dimethyl benzyne precursor 1 d was nicely converted to the dimethylphenyl‐triflone 2 d in 76 % yield (entry 4). The 5‐trimethylsilyl‐6‐trifluoromethanesulfonyloxy indane 1 e also provided the corresponding 5‐trifluoromethanesulfonylated indane 2 e in 74 % yield (entry 5).

Table 2.

Trifluoromethanesulfonylation of symmetrical benzyne precursors 1 a–e.^[a]

Entry	Substrate	Product	Yield [%]
1			50
2			43
3			63
4			76
5			74

[a] Reaction was carried out with 1, NaSO₂CF₃ (2.0 equiv), CsF (6.0 equiv), 15‐crown‐5 (2.0 equiv), and tBuOH (1.0 equiv) in MeCN (1.0 mL) at 40 °C for 3 h.

We next investigated the trifluoromethanesulfonylation of unsymmetrical benzynes generated from 4‐ or 6‐substituted 1‐trimethylsilyl‐2‐trifluoromethanesulfonate arenes 1 f–n (Table 3). 4‐Methyl benzyne precursor 1 f gave a mixture of aryl triflones 2 f and 2 f’ in a 48:52 regioisomeric ratio in a combined yield of 58 % (entry 1). The bulky tBu‐substituted benzyne precursor 1 g gave the corresponding regioisomeric aryl triflones 2 g and 2 g’ in 47 % yield in a ratio of 33:67 (entry 2). 4‐Methoxy‐substituted benzyne precursor 1 h provided regioisomeric products 2 h and 2 h’ in 57 % yield (ratio, 74:26) selectively (entry 3). High regioselectivities were observed by the reaction of halogen‐substituted benzyne precursors 1 i and 1 j to furnish the aryl triflones 2 i and 2 i’ in 63 % yield (ratio, 81:19) and 2 j and 2 j’ in 41 % yield (ratio, 85:15), respectively (entries 4 and 5). On the other hand, phenyl‐substituted benzyne precursor 1 k gave the aryl triflones 2 k and 2 k’ in 77 % yield in a ratio of 48:52 at a higher reaction temperature (50 °C) (entry 6). The unsymmetrical naphthalene‐containing aryne precursor 1 l provided the trifluoromethanesulfonylated naphthalenes 2 l (2 a) and 2 l’ (2 a’) in 64 % yield in a ratio of 67:33 (entry 7). It should be pointed out that 6‐substituted 1‐trimethylsilyl‐2‐trifluoromethanesulfonate benzyne precursors 1 m and 1 n solely provided the 3‐substituted phenyl triflones 2 m’ (2 h’) and 2 n’ (2 j’) in moderate yields, 42 and 27 %, respectively (entries 8 and 9).

Table 3.

Trifluoromethanesulfonylation of unsymmetrical benzyne precursors 1 f–n.^[a]

Entry	Substrate	Product	Yield[b] [%]
1			58 (48:52)
2			47 (33:67)
3			57 (74:26)
4			63 (81:19)
5			41 (85:15)
6[c]			77 (48:52)
7			64 (67:33)
8			42 (100:0)
9			27 (100:0)

[a] Reaction was carried out with 1 a, NaSO₂CF₃ (2.0 equiv), CsF (6.0 equiv), 15‐crown‐5 (2.0 equiv), tBuOH (1.0 equiv) in MeCN (1.0 mL) at 40 °C for 3 h. [b] The ratios of regioisomers are shown in parentheses and were determined by crude products of ¹⁹F NMR spectroscopy. [c] Carried out at 50 °C.

According to previous studies of regioselectivity of substituted benzynes,14, 21 the regioselectivity observed in Table 2 could be rationally explained by both the balance of polarization of the electric charge and steric hindrance of the benzyne intermediates I (Scheme 2). Initially, Cs⁺ is captured by 15‐crown‐5 to generate naked fluoride anion, which attacks the silicon atom of 1 to generate highly reactive benzynes I. Then, SO₂CF₃ anion attacks benzynes I followed by protonation with tBuOH to provide desired aryl triflones 2 (Scheme 2). The formation of the major meta‐isomer 2 g’ (R=tBu) can be explained by the preferential attack of the SO₂CF₃ anion to C3, as C4 is more negative because of the electron‐donating effect of the tBu substituent (positive inductive effect, Figure 1 a).21, 22 On the other hand, for the MeO‐, Cl‐ and Br‐substituted benzynes, the major products are para‐substituted regioisomers 2 h, 2 i, and 2 j, indicating that the developing positive charge at the C4 position by the strong electron negativity of O(Me), Cl, and Br (negative inductive effect) should be the main factor controlling regioselectivity (Figure 1 b).18h, 21 In contrast, no selectivity in the reaction of 1 f and 1 k (R=Me, Ph) suggests that there is no significant difference between steric and electronic factors on C3 and C4 (Figure 1 c).22 Complete regioselective formation of meta‐substituted isomers 2 m’ (2 h’) and 2 n’ (2 j’) from 1 m and 1 n should be explained by both the steric effect and polarization of the electric charge on C2 and C3 (Figure 1 d).21, 22 The preferred formation of 2‐SO₂CF₃ naphthalene 2 l (2 a) is the result of sterically favored attack on C2, owing to the steric repulsion by peri‐hydrogen in the 1,2‐naphthalyne (Figure 1 e).22

Scheme 2.

Proposed reaction mechanism for the reaction of 1 to 2.

Figure 1.

Proposed explanation of regioselectivity.

Finally, the regioselectivity was analyzed by computations. The structures of benzynes were initially optimized by density functional theory (DFT) [B3LYP/6‐31G(d)],23 and then the electron densities of their reacting π orbitals were calculated by using a natural bond orbital (NBO) 6.0.24, 25 The differences of the electron densities in the π orbital at the triple bond are shown in Figure 2 and they are in good agreement with the experimental observations of the selectivity. In the case of 1‐tBu substitution of 3,4‐benzyne, the electron density in the π orbital at C3 (0.9103) was lower than that at C4 (0.9576) (Figure 2 a). On the other hand, the electron densities in the π orbitals at C4 of 1‐Cl‐ and Br‐substituted 3,4‐benzynes were lower than those at C3 (Figure 2 b). For 1‐OMe‐substituted 3,4‐benzyne, the direction of the Me group against the triple bond strongly affected the bias of the electron density, and the electron densities in the cis‐configuration of 1‐OMe 3,4‐benzyne are in good agreement with the experimental observation, whereas those of trans‐configuration are not. In the case of Me‐ and Ph‐substituted 3,4‐benzyne, the difference between the electron densities are small, resulting in low regioselectivities (Figure 2 c). Excellent regioselectivity was observed for MeO‐ and Br‐substituted 2,3‐benzynes, which could be well explained based on the large difference of electron densities in the π orbital at C3 and C2 (Figure 2 d). The preferred formation of 2‐SO₂CF₃ naphthalene is also in good agreement with the calculations (Figure 2 e).

Figure 2.

NBO analysis of substituted benzynes. Optimized structures of benzynes were calculated by using DFT [B3LYP6/31G(d)]. The electron densities of the reacting p orbitals were determined by NBO analysis. The arrow indicates the preferred direction of selectivity.

3. Conclusions

We have succeeded in synthesizing aryl triflones through the direct trifluoromethanesulfonylation of benzynes. A wide variety of 1‐trimethylsilyl‐2‐trifluoromethanesulfonate arenes are feasible as precursors to generate highly reactive benzynes upon treatment with CsF and 5‐crown‐15 followed by the reaction with NaSO₂CF₃ to furnish a variety of aryl triflones in moderate to good yields. Regioselective trifluoromethanesulfonylation was achieved, depending on the substrate structures and selectivity, by balancing the polarization of electric charge and steric hindrance of the benzyne intermediates. All aryl triflones are expected to serve as building blocks for biologically active molecules and materials. As excess amounts of the reagents are necessary in the present method, further improvement of the reaction conditions are required. Applications of this methodology, including the synthesis of heteroaryl triflones,4 are also under investigation.

Experimental Section

General Procedure of Trifluoromethanesulfonylation

To a stirred solution of 2‐(trimethylsilyl)aryl trifluoromethanesulfonates 1 26 (0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv) in acetonitrile (1.0 mL) was added with 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) at room temperature under a nitrogen atmosphere. After the reaction mixture was stirred at 40 °C for 3 h, it was cooled to room temperature, water was added, and the whole mixture was extracted with Et₂O. The combined organic layers were washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure to give the crude product. The residue was purified by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel to give trifluoromethanesulfonyl benzenes 2.

1. ‐(Trifluoromethylsulfonyl)naphthalene (2 a)5g, 11f

A reaction of 2‐(trimethylsilyl)naphthalen‐3‐yl trifluoromethanesulfonate 1 a (34.8 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave 2‐(trifluoromethylsulfonyl)naphthalene 2 a (13.1 mg, 50 %) as a yellow solid.

2 a: ¹H NMR (CDCl₃, 300 MHz) δ: 7.69–7.81 (m, 2 H), 7.94–8.01 (m, 2 H), 8.06–8.11 (m, 2 H), 8.67 (s, 1 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.7 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 119.9 (q, J=325.9 Hz), 123.7, 128.0, 128.1, 128.3, 129.8, 130.2, 130.8, 132.0, 134.0 (m), 136.5 ppm; IR (KBr): 3422, 3057, 2928, 2367, 1922, 1822, 1736, 1624, 1588, 1503, 1454, 1363, 1271, 1213, 1124, 1064, 1019, 955, 911, 857, 812, 746, 664, 578, 469 cm⁻¹; mp (CHCl₃): 61.0–62.0 °C; MS (EI, m/z): 260 (M+); HRMS (EI): calcd for C₁₁H₇F₃O₂S: 260.0119, found: 260.0135.

2. ‐(Trifluoromethylsulfonyl)benzene (2 b)11f, 27

A reaction of 2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 b (29.8 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave 1‐(trifluoromethylsulfonyl)benzene 2 b (9.0 mg, 43 %) as a colorless oil.

2 b: ¹H NMR (CDCl₃, 300 MHz) δ: 7.67–7.72 (m, 2 H), 7.83–7.88 (m, 1 H), 8.06 (d, J=8.1 Hz, 2 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.9 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 119.8 (q, J=325.9 Hz), 129.9, 130.8, 131.3, 136.6 ppm; IR (NaCl): 2360, 1844, 1793, 1771, 1734, 1716, 1699, 1684, 1653, 1635, 1616, 1576, 1558, 1541, 1521, 1507, 1473, 1456, 1437, 1418, 1373, 1074 cm⁻¹; MS (EI, m/z): 141 (M‐CF₃ ⁺)^; HRMS (EI): calcd for C₆H₅O₂S: 141.0010, found: 141.0055.

3. ,2‐Dimethyl‐4‐(trifluoromethylsulfonyl)benzene (2 c)

A reaction of 4,5‐dimethyl‐2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 c (32.6 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave 1,2‐dimethyl‐4‐(trifluoromethylsulfonyl)benzene 2 c (15.1 mg, 63 %) as a white solid.

2 c: ¹H NMR (CDCl₃, 300 MHz) δ: 2.39 (s, 3 H), 2.41 (s, 3 H), 7.42 (d, J=7.5 Hz, 1 H), 7.76–7.78 (m, 2 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −79.2 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 19.8, 20.3, 119.8 (q, J=325.9 Hz), 128.1, 128.3, 131.0, 131.2, 139.0, 147.1 ppm; IR (KBr): 3083, 2952, 2877, 2609, 2375, 1930, 1790, 1654, 1596, 1483, 1451, 1362, 1304, 1216, 1125, 1082, 1024, 893, 826, 763, 705, 672, 608, 509 cm⁻¹; mp (CHCl₃): 50.5–51.5 °C; MS (EI, m/z): 238 (M⁺); HRMS (EI): calcd for C₉H₉F₃O₂S: 238.0275, found: 238.0296.

4. ,4‐Dimethyl‐2‐(trifluoromethylsulfonyl)benzene (2 d)

A reaction of 3,6‐dimethyl‐2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 d (32.6 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave 1,4‐dimethyl‐2‐(trifluoromethylsulfonyl)benzene 2 d (18.0 mg, 76 %) as a colorless oil.

2 d: ¹H NMR (CDCl₃, 300 MHz) δ: 2.43 (s, 3 H), 2.68 (s, 3 H), 7.32 (d, J=7.5 Hz, 1 H), 7.48 (d, J=7.5 Hz, 1 H) 7.88 (s, 1 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.8 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 20.1, 20.6, 120.1 (q, J=326.4 Hz), 129.3, 133.3, 133.5, 137.2, 137.4, 139.0 ppm; IR (NaCl): 2932, 2372, 2351, 2326, 1653, 1558, 1495, 1456, 1393, 1361, 1283, 1215, 1125, 1059, 885, 826, 764, 701, 615, 588, 530, 481, 425, 412 cm⁻¹; MS (EI, m/z): 238 (M⁺); HRMS (EI): calcd for C₉H₉F₃O₂S: 238.0275, found: 238.0298.

5. ,3‐Dihydro‐5‐(trifluoromethylsulfonyl)‐1H‐indene (2 e)

A reaction of 2,3‐dihydro‐5‐(trimethylsilyl)‐1H‐inden‐6‐yl trifluoromethanesulfonate 1 e (33.8 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave 2,3‐dihydro‐5‐(trifluoromethylsulfonyl)‐1H‐indene 2 e (18.5 mg, 50 %) as a white solid.

2 e: ¹H NMR (CDCl₃, 300 MHz) δ: 2.14–2.24 (m, 2 H), 3.02–3.07 (m, 4 H), 7.49 (d, J=7.8 Hz, 1 H), 7.82 (d, J=7.8 Hz, 1 H), 7.85 (s, 1 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −79.1 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 25.2, 32.5, 33.2, 119.9 (q, J=325.9 Hz), 125.6, 126.4, 128.7, 129.2, 146.5, 154.8 ppm; IR (KBr): 3066, 2969, 1931, 1814, 1598, 1573, 1437, 1413, 1363, 1216, 1063, 886, 828, 763, 686, 607, 518, 460, 417 cm⁻¹; mp: 58.0–59.0 °C (CHCl₃); MS (EI, m/z): 250 (M⁺); HRMS (EI): calcd for C₁₀H₉F₃O₂S: 250.0275, found: 250.0302.

6. ‐Methyl‐4‐(trifluoromethylsulfonyl)benzene (2 f)28 and 1‐Methyl‐3‐(trifluoromethylsulfonyl)benzene (2 f’)28

A reaction of 4‐methyl‐2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 f (31.2 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave inseparable mixture of 1‐methyl‐4‐(trifluoromethylsulfonyl)benzene 2 f and 1‐methyl‐3‐(trifluoromethylsulfonyl)benzene 2 f’ (12.8 mg, 57 %, 48:52) as a colorless oil.

Mixture of 2 f and 2 f’: ¹H NMR (CDCl₃, 300 MHz) δ: 2.50 (s, 3 H), 2.52 (s, 3 H), 7.47 (d, J=7.8 Hz, 2 H), 7.53–7.58 (m, 1 H), 7.63–7.65 (m, 1 H), 7.82–7.86 (m, 2 H), 7.93 (d, J=8.4 Hz, 2 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −79.1(minor, s, 3F, 2 f), −79.0 (major, s, 3F, 2 f’) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 21.2, 21.9, 119.77 (q, J=325.9 Hz), 119.80 (q, J=325.9 Hz), 127.9, 128.1, 129.7, 130.5, 130.7, 130.8, 131.1, 137.4, 140.4, 148.4 ppm; IR (NaCl): 3070, 2930, 2372, 2322, 1596, 1477, 1365, 1310, 1210, 1140, 1078, 866, 816, 791, 763, 698, 683, 664, 613, 590, 561, 530, 518 cm⁻¹; MS (EI, m/z): 224 (M⁺); HRMS (EI): calcd for C₈H₇F₃O₂S: 224.0119, found: 224.0134.

7. ‐tertButyl‐4‐(trifluoromethylsulfonyl)benzene (2 g)5g, 11f and 1‐tertButyl‐3‐(trifluoromethylsulfonyl)benzene (2 g’)

A reaction of 4‐tert‐butyl‐2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 k (35.4 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave a mixture of 1‐tert‐butyl‐4‐(trifluoromethylsulfonyl)benzene 2 g and 1‐tert‐butyl‐3‐(trifluoromethylsulfonyl)benzene 2 g’ (16.1 mg, 77 %, 33:67) as a colorless oil.

Mixture of 2 g and 2 g’: ¹H NMR (CDCl₃, 300 MHz) δ: 1.38 (s, 9 H), 7.60 (t, J=8.0 Hz, 0.66 H), 7.74 (d, J=8.7 Hz, 0.66 H), 7.87 (d, J=7.8 Hz, 1.33 H), 7.94 (d, J=8.4 Hz, 0.66 H), 8.02 (s, 0.66 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −79.1 (minor, s, 3F, 2 g), −79.0 (major, s, 3F, 2 g’) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 30.8, 30.9, 35.2, 35.6, 119.79 (q, J=325.9 Hz), 119.82 (q, J=325.4 Hz), 127.0, 127.4, 127.9, 128.0, 129.6, 130.6, 130.9, 133.9, 153.7, 161.2 ppm; IR (NaCl): 2968, 2309, 1593, 1482, 1368, 1217, 1146, 1079, 840, 781, 692, 678, 631, 591, 497, 467, 457, 439 cm⁻¹; MS (EI, m/z): 266 (M⁺), HRMS (EI): calcd for C₁₁H₁₃F₃O₂S: 266.0588, found: 266.0631.

8. ‐Methoxy‐4‐(trifluoromethylsulfonyl)benzene (2 h)11f, 27, 28 and 1‐Methoxy‐3‐(trifluoromethylsulfonyl)benzene (2 h’ (2 m’))

Synthesis from 1 h: A reaction of 4‐methoxy‐2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 h (32.8 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave 1‐methoxy‐4‐(trifluoromethylsulfonyl)benzene 2 h and 1‐methoxy‐3‐(trifluoromethylsulfonyl)benzene 2 h’ (15.1 mg, 63 %, 74:26) as a colorless oil.

Synthesis from 1 m: A reaction of 6‐methoxy‐2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 m (32.8 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave 1‐methoxy‐3‐(trifluoromethylsulfonyl)benzene 2 m’ (2 h’) (10.0 mg, 42 %) as a colorless oil.

2 h: Colorless oil. ¹H NMR (CDCl₃, 300 MHz) δ: 3.94 (s, 3 H), 7.11 (d, J=9.0 Hz, 2 H), 7.97 (d, J=9.3 Hz, 2 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −79.4 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 55.9, 115.2, 119.8 (q, J=325.4 Hz), 121.7, 133.1, 166.2 ppm; IR (NaCl): 3103, 2951, 2847, 2593, 2345, 1594, 1577, 1498, 1464, 1442, 1362, 1318, 1275, 1216, 1191, 1141, 1075, 1022, 837, 805, 805, 763, 673, 590 cm⁻¹; MS (EI, m/z): 240 (M⁺); HRMS (EI) calcd for C₈H₇F₃O₃S: 240.0068, found: 240.0093.

2 h’: Colorless oil. ¹H NMR (CDCl₃, 300 MHz) δ: 3.91 (s, 3 H), 7.35 (d, J=8.1 Hz, 1 H), 7.50 (s, 1 H), 7.55–7.66 (m, 2 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.8 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 55.9, 114.6, 119.8 (q, J=325.9 Hz), 122.9, 123.2, 130.9, 132.3, 160.4 ppm; IR (NaCl): 3084, 3016, 2946, 2844, 1732, 1600, 1483, 1436, 1368, 1329, 1292, 1249, 1216, 1134, 1089, 1072, 1038, 857, 790, 763, 695, 623, 587, 469 cm⁻¹; MS (EI, m/z): 240 (M⁺); HRMS (EI): calcd for C₈H₇F₃O₃S: 240.0068, found: 240.0089.

9. ‐Chloro‐4‐(trifluoromethylsulfonyl)benzene (2 i)5g, 28 and 1‐Chloro‐3‐(trifluoromethylsulfonyl)benzene (2 i’)28

A reaction of 4‐chloro‐2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 i (33.3 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave a mixture of 1‐chloro‐4‐(trifluoromethylsulfonyl)benzene 2 i and 1‐chloro‐3‐(trifluoromethylsulfonyl)benzene 2 i’ (10.0 mg, 41 %, 81:19) as a white semisolid.

2 i: White solid. ¹H NMR (CDCl₃, 300 MHz) δ: 7.67 (d, J=6.9 Hz, 2 H), 7.99 (d, J=7.2 Hz, 2 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.8 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 119.6 (q, J=325.4 Hz), 129.7, 130.4, 132.1, 144.0 ppm; IR (KBr): 3421, 3099, 2963, 2367, 1719, 1580, 1475, 1397, 1373, 1327, 1261, 1220, 1142, 1092, 1073, 1014, 804, 770, 702, 631, 580, 472 cm⁻¹; mp: 49.0–50.0 °C (CHCl₃); MS (EI, m/z): 111 (M‐SO₂CF₃ ⁺), HRMS (EI): calcd for C₆H₄Cl: 111.0002, found: 110.9991.

2 i’: Colorless oil. ¹H NMR (CDCl₃, 300 MHz) δ: 7.64 (t, J=8.0 Hz, 1 H), 7.82 (d, J=8.1 Hz, 1 H), 7.95 (d, J=8.1 Hz, 1 H), 8.03 (s, 1 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.5 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 119.6 (q, J=325.9 Hz), 128.9, 130.6, 131.1, 133.1, 136.4, 136.8 ppm; IR (NaCl): 3075, 2920, 2850, 2352, 1725, 1578, 1462, 1411, 1373, 1305, 1215, 1146, 1103, 1074, 889, 793, 760, 672, 612, 582, 534, 521, 499, 488 cm⁻¹; MS (EI, m/z): 111 (M‐SO₂CF₃ ⁺), HRMS (EI): calcd for C₆H₄Cl: 111.0002 Found: 111.0009.

10. ‐Bromo‐4‐(trifluoromethylsulfonyl)benzene (2 j)5g, 27, 28 and 1‐Bromo‐3‐(trifluoromethylsulfonyl)benzene (2 j’ (2 n’))5g

Synthesis from 1 j: A reaction of 4‐bromo‐2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 j (37.7 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave 1‐bromo‐4‐(trifluoromethylsulfonyl)benzene 2 j and 1‐bromo‐3‐(trifluoromethylsulfonyl)benzene 2 j’ (13.5 mg, 47 %, 85:15) as a white semisolid.

Synthesis from 1 n: A reaction of 6‐bromo‐2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 n (37.7 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown 5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) acetonitrile (1.0 mL) proceeded at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave 1‐bromo‐3‐(trifluoromethylsulfonyl)benzene 2 n’ (2 j’) (7.9 mg, 27 %) as a white solid.

2 j: White solid. ¹H NMR (CDCl₃, 300 MHz) δ: 7.83 (d, J=8.4 Hz, 2 H), 7.90 (d, J=8.7 Hz, 2 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.8 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 119.6 (q, J=325.9 Hz), 130.2, 132.0, 132.8, 133.4 ppm; IR (KBr): 3098, 2957, 2562, 2370, 2344, 1719, 1573, 1469, 1373, 1218, 1139, 1070, 1011, 826, 767, 699, 617, 578, 524, 474, 418 cm⁻¹; mp: 63.5–64.5 °C (CHCl₃); MS (EI, m/z): 219 (M‐CF₃ ⁺), HRMS (EI): calcd for C₆H₄BrO₂S: 218.9115, found: 218.9143.

2 j’: Colorless oil; ¹H NMR (CDCl₃, 300 MHz) δ:7.55–7.61 (m, 1 H), 7.97–8.00 (m, 2 H), 8.19 (s, 1 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.5 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 119.6 (q, J=325.9 Hz), 123.9, 129.3, 131.3, 133.2, 133.4, 139.7 ppm; IR (NaCl): 3088, 2929, 2352, 1717, 1572, 1460, 1406, 1373, 1302, 1215, 1145, 1073, 782, 674, 658, 610, 580, 523, 498, 480, 452, 436, 425, 407 cm⁻¹; MS (EI, m/z): 288 (M⁺), HRMS (EI): calcd for C₇H₄BrF₃O₂S: 287.9067, found: 287.9132.

11. ‐(Trifluoromethylsulfonyl)biphenyl (2 k) ^[5g, 11f] and 3‐(Trifluoromethylsulfonyl)biphenyl (2 k’)

A reaction of 4‐phenyl‐2‐(trimethylsilyl)phenyl trifluoromethanesulfonate 1 k (29.8 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceeded at 50 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave 4‐(trifluoromethylsulfonyl)biphenyl 2 k and 3‐(trifluoromethylsulfonyl)biphenyl 2 k’ (18.3 mg, 64 %, 48:52) as a white solid.

2 k: White solid. ¹H NMR (CDCl₃, 300 MHz) δ: 7.45–7.54 (m, 3 H), 7.62–7.65 (m, 2 H), 7.86 (d, J=7.8 Hz, 2 H), 8.09 (d, J=8.4 Hz, 2 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.9 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 119.8 (q, J=325.4 Hz), 127.5, 128.4, 129.25, 129.33, 129.5, 131.3, 138.4, 149.6 ppm; IR (KBr): 3071, 2567, 2347, 1937, 1814, 1686, 1593, 1561, 1479, 1449, 1401, 1359, 1318, 1293, 1212, 1139, 1071, 1005, 847, 767, 677, 608, 580, 526 cm⁻¹; mp (CHCl₃): 76.5–77.5 °C; MS (EI, m/z): 286 (M⁺), HRMS (EI): calcd for C₁₃H₉F₃O₂S: 286.0275, found: 286.0271.

2 k’: Colorless oil. ¹H NMR (CDCl₃, 300 MHz) δ: 7.43–7.53 (m, 3 H), 7.60–7.62 (m, 2 H), 7.71–7.76 (m, 1 H), 8.00–8.05 (m, 2 H), 8.23 (s, 1 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.8 (s, 3F) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 119.8 (q, J=325.9 Hz), 127.2, 128.8, 129.0, 129.2, 129.3, 130.3, 131.9, 135.1, 138.2, 143.4 ppm; IR (NaCl): 3068, 3035, 1595, 1471, 1453, 1411, 1367, 1311, 1283, 1216, 1138, 1080, 1047, 1022, 994, 901, 811, 756, 698, 627, 587, 548, 523 cm⁻¹; MS (EI, m/z): 286 (M⁺), HRMS (EI): calcd for C₁₃H₉F₃O₂S: 286.0275, found: 286.0255.

12. ‐(Trifluoromethylsulfonyl)naphthalene (2 l (2 a)) and 1‐(Trifluoromethylsulfonyl)naphthalene (2 l’ (2 a’))5g

A reaction of 1‐(trimethylsilyl)naphthalen‐2‐yl trifluoromethanesulfonate 1 l (34.8 mg, 0.1 mmol), sodium trifluoromethanesulfinate (31.2 mg, 0.2 mmol, 2.0 equiv), 15‐crown‐5 (39.7 μL, 0.2 mmol, 2.0 equiv), tert‐butyl alcohol (9.5 μL, 0.1 mmol, 1.0 equiv), and cesium fluoride (91.2 mg, 0.6 mmol, 6.0 equiv) in acetonitrile (1.0 mL) proceed at 40 °C for 3 h. Subsequent purification by column chromatography (n‐hexane/ethyl acetate=95/5) on silica gel gave inseparable mixture of 2‐(trifluoromethylsulfonyl)naphthalene 2 l (2 a) and 1‐(trifluoromethylsulfonyl)naphthalene 2 l’ (2 a’) (15.8 mg, 58 %, 67:33) as a yellow semisolid.

Mixture of 2 l (2 a) and 2 l’ (2 a’): ¹H NMR (CDCl₃, 300 MHz) δ: 7.67–7.82 (m, 2.32 H), 7.94–8.01 (m, 1.33 H), 8.06–8.11 (m, 1.66 H), 8.31 (d, J=8.4 Hz, 0.33 H), 8.47 (d, J=7.8 Hz, 0.33 H), 8.67 (s, 0.66 H), 8.82 (d, J=9 Hz, 0.33 H) ppm; ¹⁹F NMR (CDCl₃, 282 MHz) δ: −78.7 (major, s, 3F, 2 l (2 a)), −78.3 (minor, s, 3F, 2 l’ (2 a’)) ppm; ¹³C NMR (CDCl₃, 150.9 MHz) δ: 119.9 (q, J=325.9 Hz), 120.2 (q, J=327.0 Hz), 123.6, 124.3, 124.4, 126.7, 127.7, 127.9, 128.1, 128.3, 129.2, 129.6, 129.8, 130.0, 130.1, 130.8, 132.0, 134.0 (m), 134.2, 135.1, 136.5, 138.4 ppm IR (KBr): 3057, 2963, 2318, 1717, 1624, 1588, 1506, 1456, 1362, 1261, 1213, 1114, 1065, 1020, 972, 857, 812, 747, 663, 578, 513, 470 cm⁻¹; MS (EI, m/z): 260 (M⁺); HRMS (EI): calcd for C₁₁H₇F₃O₂S: 260.0119, found: 260.0133.

Conflict of interest

The authors declare no conflict of interest.

Supporting information

As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.

Supplementary

Y. Sumii, Y. Sugita, E. Tokunaga, N. Shibata, ChemistryOpen 2018, 7, 204.