AgSCF₃-mediated trifluoromethylthiolation of α,α-diaryl allylic alcohols via radical neophyl rearrangement

Abstract

A novel example of AgSCF₃-mediated oxidative radical trifluoromethylthiolation of α,α-diaryl allylic alcohols is presented, producing various α-aryl-β-trifluoromethylthiolated carbonyl ketones via radical neophyl rearrangement under mild conditions. This protocol involves formation of C(Ar)–C(sp³) and C(sp³)–S bonds in one step and tolerates a wide range of symmetrical and nonsymmetrical α,α-diaryl allylic alcohols.

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Introduction

Fluorine-containing functional groups have achieved great application in many pharmaceuticals and agrochemicals because of their remarkable potential for modulating molecular chemical, physical, and biochemical properties.¹ Among these intriguing fluorine-containing groups, the trifluoromethylthio (SCF₃) group has attracted increasing attention because of its special biological properties such as enhancement of membrane permeability and absorption rate and improvement of the stability of parent molecules, due to its high electronegativity and lipophilicity.² This has led to growing interest in developing new routes to incorporating the trifluoromethylthio group into organic molecules of interest.³ To date, numerous nucleophilic and electrophilic SCF₃ reagents have been developed to construct C–SCF₃, and these reagents are widely used because they require mild conditions and show satisfied substrate scope.^4,5 Recently, the efficient radical-type protocols for constructing C–SCF₃ using a combination of AgSCF₃ and oxidant have drawn great attention, but only a few protocols focused on the difunctionalization of alkene have been reported.^6–8

In 2014, the first radical silver-mediated oxidative aryltrifluoromethylthiolation of activated alkenes was reported by Wang group (Scheme 1a).^7a Subsequently, an intramolecular oxytrifluoromethylthiolation of unactivated alkenes was reported (Scheme 1b).^7b Soon afterward, the Qing group demonstrated direct trifluoromethylthiolation of an unactivated terminal alkene, affording various allyl trifluoromethyl sulfides (Scheme 1c).^7c In the following year, the same group reported another radical protocol for the trifluoromethylthiolation of quinones (Scheme 1d).^7d Recently, the Nevado group has reported a silver-catalyzed radical cascade trifluoromethylthiolation affording highly functionalized heterocyclic scaffolds (Scheme 1e).^7e Despite these achievements, new methods involving difunctionalization-type trifluoromethylthiolation of alkenes remain highly desirable.

Scheme 1 Radical-initiated trifluoromethylthiolation of alkenes.

Recently, the neophyl rearrangement as an efficient and ingenious strategy to constructing multiple chemical structures and reorganizing molecular skeletons has attracted increasing attention.^9–14 Inspired by the Tu semipinacol rearrangement protocol¹⁵ and recent literatures for forming β-trifluoromethyl ketones⁹ and previous advances in silver-mediated radical additions,¹⁶ we speculated that a neophyl-type rearrangement could be triggered after adding SCF₃ radical to α,α-diaryl allylic alcohols, generating α-aryl-β-trifluoromethylthiolated carbonyl ketones which suffered from poor yield in previous literature.¹⁷ As part of our continuing efforts at introducing fluorine-containing groups into organic molecules,¹⁸ we report here a novel SCF₃ radical-initiated radical neophyl rearrangement of α,α-diaryl allylic alcohols to afford trifluoromethylthiolated carbonyl ketones under mild conditions (Scheme 1f).

Result and discussion

Previous study showed that the SCF₃ radical could be efficiently generated from AgSCF₃ using K₂S₂O₈ as an oxidant.^6–8 Therefore we began our studies using α,α-diphenylprop-2-en-1-ol (1a) as substrate in the presence of AgSCF₃ (1.5 equiv.) in CH₃CN at 65 °C. A wide range of oxidants, including PhI(OAc)₂, TBHP (tert-butyl hydroperoxide), NFSI (N-fluorobenzenesulfonimide), Mn(OAc)₃, (NH₄)₂S₂O₈, Na₂S₂O₈ and K₂S₂O₈ were investigated for their ability to promote the reaction by generating the SCF₃ radical. To our delight, the desired product 3a was obtained using persulfate salts as the oxidants, and 2 equiv. K₂S₂O₈ gave the best yield of 26% (Table 1, entries 1–7). Decreasing the load of K₂S₂O₈ improved the yield of the reaction (Table 1, entry 8). A brief survey of various representative solvents showed that CH₃CN gave the best yield (Table 1, entries 9–13). A series of inorganic and organic bases were investigated to improve the yield further. While the inorganic or organic bases such as K₂CO₃, HMPA (hexamethylphosphoramide), DABCO (1,4-diazabicyclo[2.2.2]octane), and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) did not appreciably affect the transformation (Table 1, entries 14–19), pyridine (1 equiv.) increased the yield to 82% (entry 19). Changing the amount of pyridine did not improve yield (Table 1, entries 20 and 21). In a control experiment, we confirmed that no desired product was obtained when K₂S₂O₈ was omitted from the reaction system (entry 22).

Table 1 Optimization of conditions for reaction of 1a and 2a^a

Entry	Oxidant	Base	Solvent	Yield^b (%)
a Reactions were performed in sealed tubes containing 1a (0.20 mmol), 2a (0.30 mmol), oxidant (2 equiv.), base (1.0 equiv.), solvent (2 mL) under N2 at 65 °C for 5 h. N. D. = not detected.b Isolated yield.c K2S2O8 (1.5 equiv.) was used.d Pyridine (2 equiv.) was used.e Pyridine (0.5 equiv.) was used.
1	PhI(OAc)2	None	CH3CN	N. D.
2	TBHP	None	CH3CN	N. D.
3	NFSI	None	CH3CN	N. D.
4	Mn(OAc)3	None	CH3CN	N. D.
5	(NH4)2S2O8	None	CH3CN	15
6	Na2S2O8	None	CH3CN	22
7	K2S2O8	None	CH3CN	26
8^c	K2S2O8	None	CH3CN	30
9^c	K2S2O8	None	DCE	Trace
10^c	K2S2O8	None	EA	11
11^c	K2S2O8	None	NMP	20
12^c	K2S2O8	None	DMF	13
13^c	K2S2O8	None	DMSO	10
14^c	K2S2O8	K2CO3	CH3CN	Trace
15^c	K2S2O8	HMPA	CH3CN	Trace
16^c	K2S2O8	DABCO	CH3CN	Trace
17^c	K2S2O8	DBU	CH3CN	Trace
18^c	K2S2O8	(i-Pr)2NEt	CH3CN	45
19^c	K2S2O8	Pyridine	CH3CN	82
20^c^,^d	K2S2O8	Pyridine	CH3CN	74
21^c^,^e	K2S2O8	Pyridine	CH3CN	76
22	None	Pyridine	CH3CN	0

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After determining the standard reaction conditions, we explored the scope of this difunctionalization protocol with various α,α-diaryl allylic alcohols (1), and the corresponding products 3a–3u were obtained in moderate to good isolated yields (Table 2). Note that the minor regioisomers 3f′, 3g′, 3i′, 3j′, 3l′, 3m′ and 3n′, in which R¹ migrated instead of R², were observed as byproducts in the reactions of corresponding substrates and the yields are indicated in the parentheses. When the symmetric allylic alcohols containing para-substituted bromo-group or chloro-group underwent rearrangement, the corresponding α-aryl-β-trifluoromethylthiolated carbonyl ketones 3b and 3c were obtained in respective yields of 72% and 63%. Similarly, the symmetric allylic alcohol substituted by para-OPh gave moderate 51% yield. When allylic alcohol substituted by meta-OMe was used as the substrate, no obvious substitution effect was observed and 3e was obtained in 79% yield.

Table 2 Synthesis of products 3 from allylic alcohol 1^a,b

a Reaction conditions: 1a (0.20 mmol), 2a (0.30 mmol), K₂S₂O₈ (0.30 mmol), pyridine (0.20 mmol), CH₃CN (2 mL), 5 h, 65 °C under N₂.b Isolated yields of products 3.c The yields of minor regioisomer 3′, in which R¹ migrated instead of R², were shown in the parentheses (determined by ¹H NMR).d 3j and its isomer 3j′ were not separable.

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The allylic alcohols with a Ph group and a p-substituted-Ph group underwent p-substituted-Ph group migration as the major process, giving the corresponding products 3f–3h in 47–88% yield. Interestingly, allylic alcohols with a Ph group and a m-Cl–Ph group or a m-OMe–Ph group proceeded via the migration of the more electron-deficient aryl group, delivered the products 3i and 3j in respective yields of 47% and 45%. Allylic alcohols with a Ph group and an o-methylphenyl group delivered the Ph group-migration product 3k in 45% yield. Interestingly, allylic alcohols containing two different substituted aryl groups, also worked as substrates in the reaction, which selectively generated products 3l via migration of the 3,4-disubstituted-Ph group. For substrates with meta or para and meta substituents, the more electron-deficient aryl group migrated preferentially to afford the desired products 3m and 3n in respective yields of 56% and 57%. This unique selectivity suggested that the reaction might involve a radical neophyl rearrangement process rather than a simple semipinacol rearrangement.⁹ In the reactions generating 3o and 3p, migration of the Ph group took precedence over the pyren-2-yl and the naphthalene-2-yl, giving the respective yields of 33% and 74%. Gratifyingly, the Ph- and thiophen-2-yl-substituted allylic alcohol also worked well and afforded mainly the thiophen-2-yl-migration product 3q in good yield. Notably, the allylic alcohols with a tolyl or Ph attached to the vinyl group were also tolerated, affording the target products 3r–3u in 31–36% yield.

To gain further understanding of the reaction mechanism, the control experiments were performed (Scheme 2). When 2 equiv. of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or 2,6-di-tert-butyl-4-methylphenol (BHT) were added to the reaction, the desired transformation was completely inhibited (Scheme 2a and b). This observation is consistent with the hypothesis that the reaction proceeds via a radical pathway through single-electron transfer. When CuSCF₃ was used as the SCF₃ source, the reaction led to no product, indicating that silver plays a vital role in this transformation (Scheme 2c).

Scheme 2 Mechanistic studies of radical addition and radical neophyl rearrangement cascade reaction.

On the basis of the experimental results and previous reports,^6,10–14 a plausible mechanism is proposed as depicted in Scheme 3. AgSCF₃ is oxidized by K₂S₂O₈ firstly to generate the SCF₃ radical.⁶ Subsequent intermolecular addition of the SCF₃ radical to the double bond of allylic alcohol 1a affords radical intermediate A. Within radical intermediate A, neophyl rearrangement of the aryl group occurs via spiro[2,5]octadienyl radical B to produce intermediate C.^10–14 Another single-electron transfer from intermediate C to Ag(II) oxidant generates intermediate D, which affords product 3a by release of a proton.

Scheme 3 Plausible reaction mechanism.

Conclusions

In summary, we have developed a AgSCF₃-mediated trifluoromethylthiolation of α,α-diaryl allylic alcohols for the synthesis of various α-aryl-β-trifluoromethylthiolated carbonyl ketones. The procedure involves the formations of C(Ar)–C(sp³) and C(sp³)–S bonds in one step via SCF₃ radical addition and a radical neophyl rearrangement cascade process under mild conditions. The procedure tolerates a wide range of symmetrical and nonsymmetrical α,α-diaryl allylic alcohols. Given the frequent use of fluorine-containing compounds as bioactive agents, the convenience of this method affords an efficient approach in the future drug development and synthesis of fine chemicals.

Experimental

General

All manipulations were carried out in a sealed tube under a nitrogen atmosphere using standard Schlenk techniques. The solvents were distilled under nitrogen from sodium–benzophenone (THF, toluene, dioxane) or calcium hydride (DMF, MeCN, 1,2-DCE) before used. The α,α-diaryl allylic alcohols¹⁹ and AgSCF₃ ²⁰ were prepared according to the literature methods. Other chemicals were obtained from commercial sources, and were used without further purification. Chemical shifs (δ, ppm) in the ¹H NMR spectra were recorded using TMS as internal standard. Chemical shifts in ¹³C{¹H} NMR spectra were internally referenced to CHCl₃ (δ = 77.16 ppm).

General procedure for the synthesis of α-aryl-β-trifluoromethylthiolated carbonyl ketones

1a–u (0.2 mmol), 2a (62.7 mg, 0.3 mmol), K₂S₂O₈ (81.1 mg, 0.3 mmol), pyridine (15.8 mg, 0.2 mmol), and CH₃CN (2 mL) were mixed in an oven-dried sealed tube under N₂. The tube was sealed and heated at 65 °C for 5 h. The resulting mixture was cooled to room temperature and the solvent was evaporated under vacuum. The crude product was purified by column chromatography on silica gel to afford the product 3a–u.

1,2-Diphenyl-3-((trifluoromethyl)thio)propan-1-one (3a). The compound 3a was obtained in 82% yield (50.8 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.22 (1H, dd, J = 5.6, 14.0 Hz), 3.64 (1H, dd, J = 9.2, 14.0 Hz), 4.92 (1H, dd, J = 5.6, 9.2 Hz), 7.24–7.40 (5H, m), 7.36–7.40 (2H, m), 7.47–7.51 (2H, m), 7.92–7.95 (1H, m); ¹³C NMR (100 MHz, CDCl₃) δ 32.8, 54.6, 128.2, 128.3, 128.8, 129.0, 129.6, 131.4 (q, J = 304 Hz) 133.6, 135.9, 137.2, 197.5; ¹⁹F NMR (CDCl₃, 376 MHz) δ −41.3; HRMS (EI, TOF) calcd for C₁₆H₁₃F₃OS⁺ [M]⁺: 310.0639, found: 310.0638.

1,2-Bis(4-bromophenyl)-3-((trifluoromethyl)thio)propan-1-one (3b). The compound 3b was obtained in 72% yield (66.9 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.18 (1H, q, J = 5.7, 14.2 Hz), 3.59 (1H, q, J = 8.9, 14.2 Hz), 4.80 (1H, J = 6.8 Hz), 7.46 (2H, d, J = 7.8 Hz), 7.46 (2H, d, J = 7.7 Hz), 7.54 (2H, d, J = 7.9 Hz), 7.76 (2H, d, J = 7.8 Hz); ¹³C NMR (100 MHz, CDCl₃) δ 32.5, 53.9, 122.7, 129.2, 129.8, 130.4, 130.7 (q, J = 304 Hz), 132.3, 132.9, 134.3, 135.8, 196.2; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₁₅H₁₀Br₂O⁺ [M − H − SCF₃]⁺: 363.9087, found: 363.9105.

1,2-Bis(4-chlorophenyl)-3-((trifluoromethyl)thio)propan-1-one (3c). The compound 3c was obtained in 63% yield (47.5 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.18 (1H, dd, J = 5.8, 14.2 Hz), 3.60 (1H, dd, J = 8.9, 14.2 Hz), 4.82 (1H, t, J = 7.2 Hz), 7.20 (2H, d, J = 8.1 Hz), 7.31 (2H, d, J = 7.9 Hz), 7.38 (2H, d, J = 8.1 Hz), 7.85 (2H, d, J = 8.1 Hz); ¹³C NMR (100 MHz, CDCl₃) δ 32.6, 53.8, 129.3, 129.5, 129.9, 130.3, 131.3 (q, J = 304 Hz), 133.9, 134.5, 135.3, 140.4, 196.1; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₁₅H₁₁Cl₂O⁺ [M − SCF₃]⁺: 277.0181, found: 277.0168.

1,2-Bis(4-phenoxyphenyl)-3-((trifluoromethyl)thio)propan-1-one (3d). The compound 3d was obtained in 51% yield (50.3 mg) as colorless liquid after column chromatography (PE/EA = 50 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.20 (1H, dd, J = 5.7, 14.0 Hz), 3.62 (1H, dd, J = 9.0, 14.0 Hz), 4.80 (1H, dd, J = 5.7, 9.0 Hz), 7.13 (2H, d, J = 8.2 Hz), 7.47 (2H, d, J = 8.2 Hz), 7.55 (1H, d, J = 8.4 Hz), 7.76 (2H, d, J = 8.4 Hz); ¹³C NMR (100 MHz, CDCl₃) δ 32.9, 53.5, 117.2, 119.3, 119.5, 120.5, 123.9, 124.9, 129.5, 129.9, 130.2, 130.3, 131.4 (q, J = 304 Hz), 131.8, 155.2, 156.5, 157.5, 162.5; ¹⁹F NMR (CDCl₃, 376 MHz) δ −41.2; HRMS (EI, TOF) calcd for C₂₈H₂₁F₃O₃S⁺ [M]⁺: 494.1163, found: 494.1165.

1,2-Bis(3-methoxyphenyl)-3-((trifluoromethyl)thio)propan-1-one (3e). The compound 3e was obtained in 79% yield (58.5 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.22 (1H, dd, J = 5.6, 14.0 Hz), 3.63 (1H, dd, J = 9.2, 14.0 Hz), 3.76 (3H, s), 3.8 (3H, s), 4.85 (1H, dd, J = 5.6, 9.2 Hz), 6.78–6.88 (3H, m), 7.03–7.06 (1H, m), 7.22–7.30 (2H, m), 7.47–7.52 (2H, m); ¹³C NMR (100 MHz, CDCl₃) δ 32.7, 54.7, 55.4, 55.5, 113.2, 113.3, 113.9, 120.1, 120.5, 121.6, 129.8, 130.6, 131.4 (q, J = 304 Hz), 137.2, 138.7, 159.9, 160.3, 197.2; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₁₈H₁₇F₃O₃S⁺ [M]⁺: 370.0850, found: 370.0853.

2-(4-Chlorophenyl)-1-phenyl-3-((trifluoromethyl)thio)propan-1-one (3f). The compound 3f was obtained in 47% yield (32.3 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.19 (1H, dd, J = 5.9, 14.2 Hz), 3.61 (1H, dd, J = 8.8, 14.2 Hz), 4.89 (1H, dd, J = 5.9, 8.8 Hz), 7.21–7.23 (2H, d, J = 8.5 Hz), 7.29–7.31 (2H, m), 7.39–7.43 (2H, m), 7.51–7.55 (1H, m), 7.89–7.91 (2H, m); ¹³C NMR (100 MHz, CDCl₃) δ 32.8, 53.7, 128.9, 129.0, 129.6, 129.8, 131.3 (q, J = 304 Hz), 133.8, 134.3, 135.6, 135.7, 197.3; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₁₆H₁₂ClF₃OS⁺ [M]⁺: 344.0249, found: 344.0255.

2-(4-Bromophenyl)-1-phenyl-3-((trifluoromethyl)thio)propan-1-one (3g). The compound 3g was obtained in 67% yield (51.8 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.19 (1H, dd, J = 5.9, 14.2 Hz), 3.61 (1H, dd, J = 8.8, 14.2 Hz), 4.87 (1H, dd, J = 5.9, 8.8 Hz), 7.14–7.18 (2H, m), 7.39–7.47 (4H, m), 7.50–7.55 (1H, m), 7.89–7.91 (2H, m); ¹³C NMR (100 MHz, CDCl₃) δ 32.8, 53.8, 122.5, 128.9, 129.0, 129.9, 131.2 (q, J = 304 Hz), 132.8, 133.8, 135.6, 136.2, 197.2; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₁₅H₁₂BrO⁺ [M − SCF₃]⁺: 287.0072, found: 287.0039.

2-([1,1′-Biphenyl]-4-yl)-1-phenyl-3-((trifluoromethyl)thio)pr-opan-1-one (3h). The compound 3h was obtained in 88% yield (67.9 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.25 (1H, dd, J = 5.6, 14.2 Hz), 3.68 (1H, dd, J = 9.1, 14.2 Hz), 4.96 (1H, t, J = 6.9 Hz), 7.32–7.36 (3H, m), 7.39–7.42 (4H, m), 7.49–7.55 (5H, m), 7.97 (2H, d, J = 7.7 Hz); ¹³C NMR (100 MHz, CDCl₃) δ 32.8, 54.1, 127.1, 127.7, 128.2, 128.6, 128.8, 128.9, 129.0, 131.4 (q, J = 304 Hz), 133.6, 135.9, 136.1, 140.3, 141.2, 197.5; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₂₂H₁₇F₃OS⁺ [M]⁺: 386.0952, found: 386.0951.

2-(3-Chlorophenyl)-1-phenyl-3-((trifluoromethyl)thio)propan-1-one (3i). The compound 3i was obtained in 47% yield (32.3 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.20 (1H, dd, J = 4.0, 16.0 Hz), 3.63 (1H, dd, J = 8.0, 16.0 Hz), 4.90 (1H, dd, J = 4.0, 8.0 Hz), 7.16–7.18 (1H, m), 7.23–7.29 (3H, m), 7.42 (2H, d, J = 8.0 Hz), 7.54 (1H, d, J = 8.0 Hz), 7.91–7.94 (1H, m); ¹³C NMR (100 MHz, CDCl₃) δ 32.7, 53.9, 126.5, 128.3, 128.6, 128.9, 129.0, 130.8, 131.3 (q, J = 305 Hz), 133.9, 135.4, 135.6, 139.1, 197.0; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₁₆H₁₂ClF₃OS⁺ [M]⁺: 344.0249, found: 344.0251.

1-(3-Methoxyphenyl)-2-phenyl-3-((trifluoromethyl)thio)prop-an-1-one (3j) and 2-(3-methoxyphenyl)-1-phenyl-3-((trifluoromethyl)thio)propan-1-one (3j′). The compounds 3j and 3j′ were obtained in total 83% yield (56.4 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.21 (2H, dd, J = 5.6, 14.0 Hz), 3.64 (2H, dd, J = 9.1, 14.0 Hz), 3.77 (2.68H, s), 3.80 (3.20H, s), 4.87 (2H, m), 6.78–6.80 (2H, m), 6.87 (1H, d, J = 7.6 Hz), 7.03–7.06 (1H, m), 7.22–7.41 (9H, m), 7.46–7.52 (3H, m), 7.93–7.95 (2H, m); ¹³C NMR (100 MHz, CDCl₃) δ 32.75, 32.84, 54.6, 54.7, 55.4, 55.5, 113.2, 113.4, 113.9, 120.1, 120.6, 121.6, 128.2, 128.3, 128.8, 129.0, 129.6, 129.8, 130.6, 131.4 (q, J = 304 Hz), 133.6, 135.9, 137.2, 137.3, 138.7, 159.9, 160.4, 197.4; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₁₇H₁₅F₃O₂S⁺ [M]⁺: 340.0745, found: 340.0749.

2-Phenyl-1-(o-tolyl)-3-((trifluoromethyl)thio)propan-1-one (3k). The compound 3k was obtained in 45% yield (29.2 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 2.37 (3H, s), 3.21 (1H, dd, J = 5.4, 14.0 Hz), 3.67 (1H, dd, J = 9.5, 14.0 Hz), 4.80 (1H, dd, J = 5.4, 9.5 Hz); 7.15–7.27 (4H, m), 7.28–7.32 (4H, m), 7.57 (1H, d, J = 7.7 Hz); ¹³C NMR (100 MHz, CDCl₃) δ 21.4, 32.4, 57.0, 125.7, 128.2, 128.3, 128.5, 129.4, 131.4 (q, J = 304 Hz), 131.7, 132.0, 136.6, 137.3, 138.9, 201.2; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (ESI, TOF) calcd for C₁₇H₁₅F₃OS⁺ [M]⁺: 324.0796, found: 324.0798.

2-(3,4-Dichlorophenyl)-1-phenyl-3-((trifluoromethyl)thio)-propan-1-one (3l). The compound 3l was obtained in 66% yield (49.9 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.20 (1H, dd, J = 6.0, 14.2 Hz), 3.61 (1H, dd, J = 8.8, 14.2 Hz), 4.87 (1H, dd, J = 6.0, 8.8 Hz), 7.14 (1H, dd, J = 2.1, 8.3 Hz), 7.39–7.45 (4H, m), 7.53–7.57 (1H, m), 7.90–7.92 (2H, m); ¹³C NMR (100 MHz, CDCl₃) δ 32.7, 53.2, 127.6, 128.9, 129.0, 130.1, 130.5, 131.3 (q, J = 303 Hz), 131.5, 132.7, 133.7, 134.1, 135.5, 137.2, 196.8; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.2; HRMS (EI, TOF) calcd for C₁₆H₁₁Cl₂F₃OS⁺ [M]⁺: 377.9860, found: 377.9865.

2-(3-Bromophenyl)-1-(3-methoxyphenyl)-3-((trifluoromethyl)-thio)propan-1-one (3m). The compound 3m was obtained in 56% yield (46.7 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.20 (1H, dd, J = 5.7, 14.2 Hz), 3.62 (1H, dd, J = 9.0, 14.2 Hz), 3.82 (3H, s), 4.86 (1H, dd, J = 5.7, 9.0 Hz), 7.06–7.09 (1H, m), 7.20–7.22 (2H, m), 7.31 (1H, t, J = 8.0 Hz), 7.39–7.42 (1H, m), 7.43–7.49 (3H, m); ¹³C NMR (100 MHz, CDCl₃) δ 32.8, 54.0, 55.6, 113.2, 120.4, 121.6, 123.5, 126.9, 129.8, 129.9, 131.0, 131.1, 131.3 (q, J = 304 Hz), 131.5, 137.0, 139.4, 160.0, 196.8; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.2; HRMS (EI, TOF) calcd for C₁₇H₁₄BrF₃O₂S⁺ [M]⁺: 417.9850, found: 417.9854.

2-(4-Chlorophenyl)-1-(3-methoxyphenyl)-3-((trifluoromethyl)-thio)propan-1-one (3n). The compound 3m was obtained in 57% yield (42.6 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.19 (1H, dd, J = 5.9, 14.2 Hz), 3.60 (1H, dd, J = 8.8, 14.2 Hz), 3.81 (3H, s), 3.87 (1H, dd, J = 5.9, 8.8 Hz), 7.07 (1H, dd, J = 2.2, 7.9 Hz), 7.20–7.23 (2H, m), 7.28–7.32 (3H, m), 7.44–7.48 (2H, m); ¹³C NMR (100 MHz, CDCl₃) δ 32.7, 53.8, 55.6, 113.3, 120.2, 121.5, 129.6, 129.8, 129.9, 131.4 (q, J = 304 Hz), 134.3, 135.7, 137.0, 160.0, 197.1; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₁₇H₁₄ClF₃O₂S⁺ [M]⁺: 374.0355, found: 374.0358.

1-Phenyl-2-(pyren-2-yl)-3-((trifluoromethyl)thio)propan-1-one (3o). The compound 3o was obtained in 33% yield (28.6 mg) as yellow liquid after column chromatography (PE/EA = 50 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.37 (1H, dd, J = 4.4, 14.4 Hz), 3.84 (1H, dd, J = 10.5, 14.4 Hz), 5.97 (1H, dd, J = 4.4, 10.5 Hz), 7.21–7.26 (2H, m), 7.37 (1H, t, J = 7.4 Hz), 7.7 (1H, d, J = 8.0 Hz), 7.78–7.89 (2H, m), 7.98 (1H, d, J = 8.9 Hz), 8.03–8.09 (3H, m), 8.23 (1H, d, J = 7.4 Hz), 8.28 (1H, d, J = 7.6 Hz), 8.35 (1H, d, J = 9.3 Hz), 8.55 (1H, d, J = 9.3 Hz); ¹³C NMR (100 MHz, CDCl₃) δ 32.4, 51.0, 121.3, 124.9, 125.1, 125.6, 125.7, 125.8, 126.1, 126.5, 127.5, 128.1, 128.2, 128.8, 128.9, 129.6, 130.8, 131.0, 131.3, 131.4, 131.7 (q, J = 303 Hz), 133.5, 135.9, 198.0; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₂₆H₁₇F₃OS⁺ [M]⁺: 434.0952, found: 434.0954.

2-(Naphthalen-2-yl)-1-phenyl-3-((trifluoromethyl)thio)-propan-1-one (3p). The compound 3p was obtained in 74% yield (53.3 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.30 (1H, dd, J = 5.7, 14.1 Hz), 3.73 (1H, dd, J = 9.1, 141 Hz), 5.07 (1H, dd, J = 5.7, 9.1 Hz), 7.34–7.46 (3H, m), 7.46–7.49 (3H, m), 7.73 (1H, s), 7.77–7.84 (3H, m), 7.96–7.98 (2H, m); ¹³C NMR (100 MHz, CDCl₃) δ 32.9, 54.7, 125.7, 126.6, 126.8, 127.5, 127.9, 128.0, 128.8, 129.0, 129.6, 131.5 (q, J = 304 Hz), 132.9, 133.6, 133.7, 134.7, 135.9, 197.5; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.3; HRMS (EI, TOF) calcd for C₂₀H₁₅F₃OS⁺ [M]⁺: 360.0796, found: 360.0797.

1-Phenyl-2-(thiophen-2-yl)-3-((trifluoromethyl)thio)propan-1-one (3q). The compound 3q was obtained in 45% yield (28.5 mg) as light yellow liquid after column chromatography (eluent = petroleum ether). ¹H NMR (400 MHz, CDCl₃) δ 3.32 (1H, dd, J = 5.7, 14.2 Hz), 3.66 (1H, dd, J = 9.1, 14.0 Hz), 5.20 (1H, dd, J = 5.7, 9.1 Hz), 6.93–6.94 (2H, m), 7.23 (1H, t, J = 3.2 Hz), 7.42–7.46 (2H, m), 7.56 (1H, t, J = 7.2 Hz), 7.98 (1H, s), 7.99 (1H, s); ¹³C NMR (100 MHz, CDCl₃) δ 33.2, 48.6, 126.1, 126.8, 127.6, 128.9, 129.0, 131.3 (q, J = 304 Hz), 133.9, 135.5, 138.9, 196.4; ¹⁹F NMR (376 MHz, CDCl₃) δ −41.2; HRMS (EI, TOF) calcd for C₁₄H₁₁F₃OS₂⁺ [M]⁺: 316.0203, found: 316.0197.

1,2-Bis(4-chlorophenyl)-2-phenyl-3-((trifluoromethyl)thio)-propan-1-one (3r). The compound 3r was obtained in 36% yield (32.8 mg) as colorless liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 3.68 (2H, d, J = 12.8 Hz), 3.77 (1H, d, J = 12.8 Hz), 7.16 (2H, d, J = 8.9 Hz), 7.30–7.38 (9H, m), 7.56 (2H, d, J = 8.6 Hz); ¹³C NMR (100 MHz, CDCl₃) δ 42.0, 64.8, 128.4, 128.9, 129.0, 129.1, 129.2, 130.8 (q, J = 304 Hz), 131.0, 132.0, 133.5, 134.3, 136.9, 138.2, 139.3, 198.1; ¹⁹F NMR (376 MHz, CDCl₃) δ −42.8; HRMS (ESI, TOF) calcd for C₂₂H₁₅Cl₂F₃NaOS⁺ [M + Na]⁺: 477.0070, found: 477.0067.

1,2-Bis(4-chlorophenyl)-2-(p-tolyl)-3-((trifluoromethyl)thio)-propan-1-one (3s). The compound 3s was obtained in 31% yield (29.1 mg) as yellow liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 2.34 (3H, s), 3.65 (1H, d, J = 12.8 Hz), 3.77 (2H, d, J = 12.8 Hz), 7.14–7.18 (4H, m), 7.21 (2H, d, J = 8.4 Hz), 7.29–7.35 (4H, m), 7.55 (2H, d, J = 8.8 Hz); ¹³C NMR (100 MHz, CDCl₃) δ 21.2, 42.0, 64.5, 128.5, 128.9, 129.1, 129.8, 131.0, 132.0, 133.7, 134.2, 135.1, 137.2, 138.4, 139.2, 199.2; ¹⁹F NMR (CDCl₃, 376 MHz) δ −42.7; HRMS (EI, TOF) calcd for C₂₂H₁₇Cl₂O⁺ [M]⁺: 367.0656, found: 367.0653.

1,2-Bis(4-bromophenyl)-2-phenyl-3-((trifluoromethyl)thio)-propan-1-one (3t). The compound 3t was obtained in 39% yield (42.4 mg) as yellow liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 2.34 (3H, s), 3.67 (1H, d, J = 12.8 Hz), 3.77 (2H, d, J = 12.8 Hz), 7.24–7.27 (2H, m), 7.34–7.37 (7H, m), 7.46–7.51 (4H, m); ¹³C NMR (100 MHz, CDCl₃) δ 41.9, 64.9, 122.5, 128.2, 128.5, 129.1, 129.2, 131.3, 131.5, 132.0, 132.1, 134.0, 137.5, 138.1, 198.2; ¹⁹F NMR (CDCl₃, 376 MHz) δ −42.7; HRMS (EI, TOF) calcd for C₂₁H₁₅Br₂O⁺ [M]⁺: 440.9490, found: 440.9491.

1,2-Bis(4-bromophenyl)-2-(p-tolyl)-3-((trifluoromethyl)thio)-propan-1-one (3u). The compound 3u was obtained in 33% yield (36.8 mg) as yellow liquid after column chromatography (PE/EA = 100 : 1). ¹H NMR (400 MHz, CDCl₃) δ 2.34 (3H, s), 3.67 (1H, d, J = 12.8 Hz), 3.77 (2H, d, J = 12.8 Hz), 7.15–7.18 (2H, m), 7.23–7.26 (4H, m), 7.32–7.34 (2H, m), 7.46–7.49 (4H, m); ¹³C NMR (100 MHz, CDCl₃) δ 41.9, 64.9, 122.5, 128.2, 128.5, 129.1, 129.2, 131.3, 131.5, 132.0, 132.1, 134.0, 137.5, 138.1, 198.2; ¹⁹F NMR (CDCl₃, 376 MHz) δ −42.7; HRMS (EI, TOF) calcd for C₂₂H₁₇Br₂O⁺ [M]⁺: 454.9646, found: 454.9644.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Project No. 21421004, 21561162003, 21672059 and 21372072), the Eastern Scholar Distinguished Professor Program, the Programme of Introducing Talents of Discipline to Universities (B16017), the NCET (NCET-13-0798) and the Fundamental Research Funds for the Central Universities.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Detailed experimental procedure and characterization of products (H¹, C¹³ and F¹⁹ NMR spectra). See DOI: 10.1039/c6ra25378d

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