Photoinduced synthesis of α-trifluoromethylated ketones through the oxidative trifluoromethylation of styrenes using CF₃SO₂Na as a trifluoromethyl reagent without an external photoredox catalyst

Abstract

A photoinduced strategy to access α-CF₃-substituted ketones through the reaction of simple styrenes with sodium trifluoromethanesulfinate (CF₃SO₂Na) in the absence of an external photosensitizer under LED (380–385 nm) irradiation and an air atmosphere at room temperature was developed. This reaction employs the commercially available, low cost, and easy to handle Langlois reagent (CF₃SO₂Na) as a CF₃-radical source, and the reaction has advantages of mild conditions, a simple system and good functional group tolerance. Investigations indicated that the product acts as a photosensitizer and ¹O₂ coexists with O₂˙⁻ during the reaction through the energy transfer and single electron transfer process.

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Introduction

The trifluoromethyl group (CF₃), with electron-withdrawing nature, lipophilicity, and metabolic and chemical stability,¹ is a very useful substituent in organics,² and is prevalent in pharmaceuticals,³ materials,⁴ and agrochemicals.⁵ Hence, direct trifluoromethylation of organic compounds has received great attention.⁶ Particularly, the formation of α-CF₃ substituted ketones is very attractive, because they can be used widely as versatile building blocks for the complex CF₃-containing organic molecules. Until now, a number of trifluoromethylation reagents, such as CF₃I,⁷ CF₃SO₂Cl,⁸ Togni's reagent,⁹ Langlois reagent,¹⁰ Umemoto's reagent,¹¹ Ruppert–Prakash reagent,¹² and S-(trifluoromethyl)diphenylsulfonium triflate ([Ph₂SCF₃]⁺OTf⁻),¹³ have been recommended as effective CF₃-sources. Generally, the strategies on the synthesis of α-trifluoromethylated ketones¹⁴ depend on the electrophilic or radical trifluoromethylation of enolates, prepared from the corresponding aldehydes, ketones, esters and amides.¹⁵ However, the direct oxidative trifluoromethylation (keto-trifluoromethylation) of alkenes, which are the abundant and commonly used feedstocks, is a straightforward and concise route to obtain them. Some of the elegant examples are as follows. Maiti described an oxidative trifluoromethylation of unactivated olefins with CF₃SO₂Na as the CF₃-source for the synthesis of α-CF₃-substituted ketones catalyzed by AgNO₃/K₂S₂O₈ (Scheme 1a). In addition, Xiao developed an α-trifluoromethylation of styrenes with [Ph₂SCF₃]⁺OTf⁻ in the presence of an excess amount of HOCH₂SO₂Na, providing α-CF₃-substituted acetophenones (Scheme 1b). Recently, Cai reported an efficient method for the radical addition of olefins along with TMSCF₃ to deliver various α-trifluoromethylated ketones (Scheme 1c). Most recently, the radical trifluoromethylation by photoredox catalysis has received great attention and emerged as a hot research topic because visible light as a rich and green energy source has been shown to induce a variety of organic transformations. MacMillan's group successfully developed a generation of α-CF₃ ketones from silyl enol ethers by means of photoredox catalysis (Scheme 1d). Akita's group disclosed a photoredox catalytic system consisting of an iridium complex fac-[Ir(ppy)₃] as an effective photoredox catalyst for the oxidative trifluoromethylation of styrenes with Togni's reagent under visible-light irradiation (Scheme 1e). Among these reactions, the involvement of a trifluoromethyl radical implied that the outcome of the reaction is significantly affected by means of generating the trifluoromethyl radical.

Scheme 1 Synthesis of α-trifluoromethylated ketones from alkenes.

In general, photoredox catalysis¹⁶ as a powerful tool for organic synthesis needs a suitable photosensitizer (Ru-, Ir-, Au-complex, or organic dye). To avoid the above precious metals and expensive organic dyes used as photocatalysts, organic reactions under visible-light irradiation without the use of a photosensitizer are believed to be the direction of further research. Therefore, it is not surprising that intense research efforts have been made to develop an efficient protocol for the formation of α-CF₃-substituted carbonyl compounds via photoredox catalysis without an additional photosensitizer.¹⁷ Herein, we wish to report an efficient photoinduced synthesis of α-trifluoromethylated ketones through the oxidative trifluoromethylation of styrenes with CF₃SO₂Na (Langlois reagent) as a commercially available, stable, and easy to handle CF₃-source in the absence of an external photocatalyst under an air atmosphere, generating the corresponding products in good yields under transition-metal free and mild conditions (Scheme 1f).

At first, the reaction conditions were optimized using a model reaction of styrene (1a) with CF₃SO₂Na (2a), as shown in Table 1. When the model reaction was performed in the presence of Ru(bpy)₃Cl₂ as a photocatalyst under the irradiation of a blue LED (450–455 nm) and under an air atmosphere in acetone at room temperature for 18 h, the corresponding α-trifluoromethylated ketone 3a was provided in 24% yield (Table 1, entry 1). For the improvement of the desired product yield, a number of photocatalysts were examined. Among the tested photocatalysts, Ru(Phen)₃Cl₂, Mes-Acr-Me⁺ClO₄⁻, fac-Ir(ppy)₃, eosin Y, methylene blue and acridine red, generated 3a in 27–40% yields, and no reaction of Ru(Phen)₃(PF₆)₂, rose bengal and fluorescein were observed (Table 1, entries 2–10). To our delight, when the model reaction was carried out in the absence of any additional photocatalyst and under LED 380–385 nm irradiation in acetone, 76% yield of 3a was obtained (Table 1, entry 11). Other solvents, such as MeCN, DME, DMSO and DMF exhibited lower reactivity, generating 3a in 17–64% yields; DCE and THF showed no reactivity in the reaction (Table 1, entries 12–17). Subsequently, the wavelength of the light source was investigated and the LED (380–385 nm) was the best one for the reaction. An optical wavelength less than 380–385 nm or more than 380–385 nm exhibited lower reactivity (Table 1, entries 18–20). It should be noted that a wavelength greater 450 nm did not show any reactivity (Table 1, entries 20 and 21). When the model reaction was performed in the absence of light irradiation (in the dark) or under a nitrogen atmosphere, no desired product 3a was observed (Table 1, entries 23 and 24). Further exploration of the reaction time indicated that 18 h is an optimal choice (Table 1, entry 25).

Table 1 Optimization of the reaction conditions^a

Entry	Catalyst	Solvent	Light source	Yield^b (%)
a Reaction conditions: Styrene (1a, 0.20 mmol), CF3SO2Na (2a, 0.40 mmol), solvent (2.0 mL) at room temperature under light irradiation (1.5 W) in air for 18 h. b Isolated yield. c N2 atmosphere. d For 15 h. e For 24 h. NR = no reaction.
1	Ru(bpy)3Cl2	Acetone	450–455 nm	24
2	Ru(Phen)3Cl2	Acetone	450–455 nm	27
3	Mes-Acr-Me^+ClO4^−	Acetone	450–455 nm	40
4	fac-Ir(ppy)3	Acetone	450–455 nm	30
5	Eosin Y	Acetone	520–525 nm	21
6	Methylene blue	Acetone	520–525 nm	32
7	Acridine red	Acetone	520–525 nm	36
8	Ru(Phen)3(PF6)2	Acetone	450–455 nm	Trace
9	Rose bengal	Acetone	520–525 nm	NR
10	Fluorescein	Acetone	520–525 nm	Trace
11	—	Acetone	380–385 nm	76
12	—	CH3CN	380–385 nm	64
13	—	DME	380–385 nm	55
14	—	DMSO	380–385 nm	28
15	—	DMF	380–385 nm	17
16	—	DCE	380–385 nm	NR
17	—	THF	380–385 nm	Trace
18	—	Acetone	365–370 nm	54
19	—	Acetone	410–415 nm	38
20	—	Acetone	420–425 nm	24
21	—	Acetone	450–455 nm	Trace
22	—	Acetone	520–525 nm	NR
23	—	Acetone	380–385 nm	NR^c
24	—	Acetone	Dark	NR
25	—	Acetone	380–385 nm	76^d, 74^e

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Based on the optimized conditions in our hand, the scope of oxidative trifluoromethylation of styrenes with CF₃SO₂Na was explored. First, a variety of styrene derivatives were examined under the standard conditions, indicating a broad tolerance of substituted groups on the aromatic rings. As shown in Scheme 2, styrenes with an electron-donating group (such as Me, t-Bu, or MeO) at the para-position of the benzene rings reacted with CF₃SO₂Na to afford the corresponding products 3b–3d in 58–65% yields. On the other hand, styrenes that possessed an electron-withdrawing group, including F, Cl, Br, F₃C, Ph, CN and MeO₂C on the para-position of the phenyl rings, underwent oxidative trifluoromethylation to generate the desired products 3e–3k in 56–85% yields. Besides, the yield of 3h could increase from 56% to 85% under LED 365–370 nm irradiation for 24 h. Obviously, the reactivity of styrene with electron-withdrawing groups is higher than that with electron-donating substituents in their oxidative trifluoromethylation with CF₃SO₂Na. Moreover, styrenes with a halogen group (F, Cl or Br) on the meta-position of benzene rings also delivered the anticipated products 3l–3n in 72–77% yields, while the substrate styrene substituted by a Me or F group on the ortho-position gave the ketones (3o–3p) in lower yields owing to the steric effect. 3,5-Dimethylstyrene reacted with CF₃SO₂Na under standard reaction conditions to generate the corresponding product 3q in 53% yield. In addition, the reaction of 2-vinylnaphthalene with CF₃SO₂Na gave the corresponding product (3r) in 57% yield. Only 45% yield of 3s was obtained when 2-vinylthiophene was employed as a starting material. It should be noted that (E)-prop-1-en-1-ylbenzene worked well with CF₃SO₂Na to achieve the desired product (3t) in 51% yield. When normal alkenes, such as cyclopentene, allylbenzene, cyclooctene and benzyl vinyl ether were used as the substrates in the reactions with CF₃SO₂Na under the optimized conditions, unfortunately, no corresponding products were obtained.

Scheme 2 The scope of styrenes [reaction conditions: Styrene (1, 0.20 mmol), CF₃SO₂Na (2a, 0.40 mmol), acetone (2.0 mL), 1.5 W LED (380–385 nm), air, r.t., 18 h; isolated yield of the product; ^a under the irradiation of LED 365–370 nm for 24 h].

Under the standard reaction conditions, we tried to explore the reactivity of cyclic olefins. As shown in Scheme 3, 1,2-dihydro-naphthalene and 1,2-dihydro-indene were transformed into the corresponding cyclic trifluoromethylation ketones (3u and 3v) in moderate yields.

Scheme 3 Substrate scope of cyclic olefins [reaction conditions: Cyclic olefin (1, 0.20 mmol), CF₃SO₂Na (2a, 0.40 mmol), acetone (2.0 mL), 1.5 W LED (380–385 nm), air, r.t., 18 h; isolated yield of the product].

To further clarify the mechanism of this transformation, several control experiments were conducted, as shown in Scheme 4. When the model reaction was carried out in the presence of a radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO, 1.5 equiv.) under the standard conditions, the oxidative trifluoromethylation was completely inhibited, suggesting that a radical process might be involved in the reaction. To trap the CF₃ radical intermediate formed during the reaction, 1,1-diphenylethylene was added into the system, generating a radical coupling product 5 in 35% isolated yield.¹⁸ Additionally, in order to understand the role of oxygen in the reaction, the electron paramagnetic resonances (EPR) were recorded using 2,2,6,6-tetramethylpiperidine (TEMP) and 5,5-dimethyl-pyrroline-N-oxide (DMPO) to capture ¹O₂ and O₂˙⁻, respectively, and the resulting EPR spectra are presented in Fig. S1 and S2 of the ESI.† There was no signal when DMPO was added into a solution of 1a and 2a in air-saturated acetone without light irradiation (Fig. S1a†). But, a strong characteristic signal of an O₂˙⁻ adduct with DMPO was observed when the above solution was irradiated with LED 380–385 nm (Fig. S1b†). Meanwhile, a strong signal of the ¹O₂ adduct with TEMP was found when the above solution was irradiated with a LED (380–385 nm), but no signal was recorded without light (Fig. S2†), implying that ¹O₂ coexists with O₂˙⁻ in the reaction. Moreover, ultraviolet-visible absorption spectra of the corresponding products 3 indicated that 3 can absorb light at 380–385 nm and act as photo-sensitizers (Fig. S3–S6†), avoiding the external photocatalyst. It should be noted that the α-trifluoromethylated ketone as a product could absorb 380–385 nm light, which activates O₂ in air efficiently and accelerates the reaction, so the entire oxidative trifluoromethylation is self-sustaining in an autocatalytic manner (Fig. S7†). It is believed that singlet oxygen ¹O₂ may be generated from the interaction of O₂ in air with a photoexcited product via an energy-transfer process.

Scheme 4 The control experiments.

On the basis of the above experimental results and relevant literature, a plausible mechanism is proposed as shown in Scheme 5. Firstly, product (P) is excited by visible light irradiation (380–385 nm) to generate the excited species (P*), which then undergoes an energy transfer process with ground-state triplet oxygen ³O₂ to afford an excited-state singlet oxygen ¹O₂ with the regeneration of ground state P. The obtained singlet ¹O₂ reacts with CF₃SO₂Na (2a) via a single electron transfer (SET) process to generate O²˙⁻ and a CF₃SO₂˙ radical, which releases SO₂ and a CF₃˙ radical. The generated CF₃˙ reacts with substrate 1a to generate an intermediate A, which undergoes a reaction with the O₂ radical anion (O²˙⁻) to afford the hydroperoxide intermediate B. This intermediate B then loses H₂O and gives the desired product 3a. On the other hand, the intermediate B may also be transformed into the benzyl alcohol derivative C, which undergoes further oxidation to ketone 3a.¹⁹

Scheme 5 The proposed mechanism.

Conclusions

In conclusion, we have presented a novel, simple, and general strategy to access α-CF₃-substituted ketones by the reaction of simple styrenes with sodium trifluoromethanesulfinate (CF₃SO₂Na, Langlois reagent) in the absence of an external photosensitizer under photo-irradiation (380–385 nm) and an air atmosphere at room temperature. This reaction employs the commercially available, low cost, and easy to handle Langlois reagent that serves as a CF₃ radical source, and has advantages of mild conditions and good functional-group tolerance. Its detailed reaction mechanism is being studied in our laboratory.

Experimental section

General remarks

The ¹H NMR, ¹³C NMR and ¹⁹F NMR spectra were recorded on a 400 MHz Bruker FT-NMR spectrometer (400 MHz, 100 MHz or 376 MHz, respectively). All chemical shifts are given as δ value (ppm) with reference to tetramethylsilane (TMS) as an internal standard. The peak patterns are indicated as follows: s, singlet; d, doublet; t, triplet; m, multiplet; q, quartet. The coupling constants, J, are reported in hertz (Hz). High resolution mass spectroscopy data of the product were collected on an Agilent Technologies 6540 UHD Accurate-Mass Q-TOF LC/MS (ESI). All the solvents and commercially available reagents were purchased from commercial suppliers. Products were purified by flash chromatography on 200–300 mesh silica gels, SiO₂.

Typical procedure for α-trifluoromethylation of styrenes with CF₃SO₂Na

A 5 mL oven-dried reaction vessel equipped with a magnetic stirrer bar was charged with styrene (1a, 0.20 mmol), sodium trifluoromethanesulfinate (2a, 0.40 mmol) and acetone (2.0 mL). The reaction vessel was exposed to LED (380–385 nm, 1.5 W) irradiation at room temperature in air with stirring for 18 h. After completion of the reaction, the mixture was concentrated to yield the crude product, which was further purified by flash chromatography (silica gel, petroleum ether/ethyl acetate = 20 : 1 to 50 : 1) to give the desired product 3a.

Characterization data for all products

3,3,3-Trifluoro-1-phenylpropan-1-one (3a)^10a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 7.94–7.92 (m, 2H), 7.66–7.62 (m, 1H), 7.53–7.49 (m, 2H), 3.80 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 189.7, 135.8, 134.2, 128.9, 128.3, 124.0 (q, J = 275.3 Hz), 42.1 (q, J = 28.1 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.02.

3,3,3-Trifluoro-1-(p-tolyl)propan-1-one (3b)^10a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 7.82 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 3.77 (q, J = 10.0 Hz, 2H), 2.42 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 189.3 (d, J = 2.4 Hz), 145.3, 133.3, 129.5, 128.4, 124.1 (q, J = 275.2 Hz), 41.8 (q, J = 27.9 Hz), 21.6. ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.06.

1-(4-(tert-Butyl)phenyl)-3,3,3-trifluoropropan-1-one (3c)^14a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 7.88 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 3.78 (q, J = 10.0 Hz, 2H), 1.34 (s, 9H). ¹³C NMR (100 MHz, CDCl₃) δ: 189.3 (d, J = 2.2 Hz), 158.1, 133.3, 128.6, 125.8, 124.1 (q, J = 275.9 Hz), 41.8 (q, J = 27.9 Hz), 35.1. ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.00.

3,3,3-Trifluoro-1-(4-methoxyphenyl)propan-1-one (3d)^10a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 7.91 (d, J = 9.2 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.75 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 188.1 (d, J = 2.5 Hz), 164.3, 130.7, 128.9, 124.1 (q, J = 275.3 Hz), 114.0, 55.5, 41.7 (q, J = 27.8 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −61.98.

3,3,3-Trifluoro-1-(4-fluorophenyl)propan-1-one (3e)^10a. Colorless liquid. ¹H NMR (400 MHz, CDCl₃) δ: 7.99–7.96 (m, 2H), 7.20–7.16 (m, 2H), 3.79 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 188.2, 166.3 (d, J = 255.3 Hz), 132.3, 131.1 (d, J = 9.6 Hz), 123.9 (d, J = 275.3 Hz), 116.1 (d, J = 22.0 Hz), 42.0 (q, J = 28.2 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.06, −102.98.

1-(4-Chlorophenyl)-3,3,3-trifluoropropan-1-one (3f)^10a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 7.88 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 3.77 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 188.5, 140.9, 134.2, 129.8, 129.3, 123.8 (q, J = 275.5 Hz), 42.2 (q, J = 28.2 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −61.98.

1-(4-Bromophenyl)-3,3,3-trifluoropropan-1-one (3g)^10a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 8.05 (d, J = 8.8 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 3.84 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 188.8, 134.5, 132.3, 129.8, 129.6, 123.8 (q, J = 275.4 Hz), 42.1 (q, J = 28.3 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.00.

3,3,3-Trifluoro-1-(4-(trifluoromethyl)phenyl)propan-1-one (3h)^15a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 8.05 (d, J = 8.0 Hz), 7.78 (d, J = 8.4 Hz), 3.85 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 188.9, 138.3, 135.4 (q, J = 32.7 Hz), 128.7, 126.0 (q, J = 3.7 Hz), 123.7 (q, J = 275.4 Hz), 123.4 (q, J = 271.1 Hz), 42.4 (q, J = 28.5 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.02, −63.35.

1-((1,1′-Biphenyl)-4-yl)-3,3,3-trifluoropropan-1-one (3i)^14a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 7.98 (d, J = 8.8 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.63–7.60 (m, 2H), 7.49–7.45 (m, 2H), 7.43–7.39 (m, 1H), 3.81 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 189.2 (q, J = 2.5 Hz), 146.8, 139.4, 134.5, 129.0, 128.9, 128.5, 127.5, 127.2, 124.0 (q, J = 275.3 Hz), 42.1 (q, J = 28.1 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −61.92.

4-(3,3,3-Trifluoropropanoyl)benzonitrile (3j)^10a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 8.05 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 3.84 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 188.5, 138.5, 132.8, 128.7, 123.6 (d, J = 275.6 Hz), 117.5, 42.4 (q, J = 28.7 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −61.97.

Methyl-4-(3,3,3-trifluoropropanoyl)benzoate (3k)^10a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 8.15–8.13 (m, 2H), 8.00–7.98 (m, 2H), 3.96 (s, 3H), 3.88 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 189.3 (d, J = 2.2 Hz), 165.8, 138.7, 134.7, 129.9, 128.1, 123.8 (q, J = 275.2 Hz), 52.4, 42.3 (q, J = 28.3 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.13.

3,3,3-Trifluoro-1-(3-fluorophenyl)propan-1-one (3l). Colorless liquid. ¹H NMR (400 MHz, CDCl₃) δ: 7.72–7.70 (m, 1H), 7.65–7.62 (m, 1H), 7.54–7.48 (m, 1H), 7.37–7.32 (m, 1H), 3.79 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 188.5, 162.9 (d, J = 247.5 Hz), 137.8, 130.7 (d, J = 7.5 Hz), 124.1 (d, J = 3.1 Hz), 123.8 (q, J = 275.3 Hz), 121.3 (d, J = 21.5 Hz), 115.1 (d, J = 22.6 Hz), 42.3 (q, J = 28.5 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.13, −110.95. HRMS (EI): calcd for C₉H₆F₄O: 206.0355, found: 206.0357.

1-(3-Chlorophenyl)-3,3,3-trifluoropropan-1-one (3m)^10d. Colorless liquid. ¹H NMR (400 MHz, CDCl₃) δ: 7.91–7.90 (m, 1H), 7.82–7.79 (m, 1H), 7.62–7.59 (m, 1H), 7.48–7.44 (m, 1H), 3.79 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 188.5 (q, J = 2.3 Hz), 137.2, 135.4, 134.1, 130.3, 128.4, 126.4, 123.8 (q, J = 275.4 Hz), 42.2 (q, J = 28.3 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.05.

1-(3-Bromophenyl)-3,3,3-trifluoropropan-1-one (3n)^10d. Yellow liquid. ¹H NMR (400 MHz, CDCl₃) δ: 8.05 (s, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.42–7.38 (m, 1H), 3.78 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 188.4, 137.4, 137.0, 131.3, 130.5, 126.8, 123.7 (q, J = 275.4 Hz), 123.3, 42.1 (q, J = 28.4 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.02.

3,3,3-Trifluoro-1-(o-tolyl)propan-1-one (3o)^10a. Colorless liquid. ¹H NMR (400 MHz, CDCl₃) δ: 7.60–7.58 (m, 1H), 7.44–7.40 (m, 1H), 7.30–7.27 (m, 2H), 3.73 (q, J = 10.0 Hz, 2H), 2.53 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ: 192.7 (q, J = 2.3 Hz), 139.5, 135.9, 132.5, 132.4, 128.9, 124.0 (q, J = 275.3 Hz), 44.5 (q, J = 27.6 Hz), 21.4. ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.09.

3,3,3-Trifluoro-1-(2-fluorophenyl)propan-1-one (3p)^14a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 7.94–7.90 (m, 1H), 7.63–7.57 (m, 1H), 7.30–7.26 (m, 1H), 7.20–7.15 (m, 1H), 3.87–3.79 (m, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 187.6–187.5 (m), 162.0 (d, J = 252.7 Hz), 135.9 (d, J = 9.2 Hz), 130.8 (d, J = 1.9 Hz), 124.9–124.8 (m), 127.9–119.7 (m), 116.8 (d, J = 23.6 Hz), 43.0–46.0 (m). ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.66, −109.80.

1-(2,4-Dimethylphenyl)-3,3,3-trifluoropropan-1-one (3q). Colorless liquid. ¹H NMR (400 MHz, CDCl₃) δ: 7.55–7.53 (m, 1H), 7.11–7.10 (m, 2H), 3.73 (q, J = 10.0 Hz, 2H), 2.53 (s, 3H), 2.37 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 191.9 (q, J = 2.2 Hz), 143.5, 140.1, 133.4, 133.0, 129.5, 126.5, 124.1 (q, J = 275.3 Hz), 44.1 (q, J = 27.4 Hz), 21.7, 21.4. ¹⁹F NMR (376 MHz, CDCl₃) δ: −62.06. HRMS (EI): calcd for C₁₁H₁₁F₃O: 216.0762, found: 216.0768.

3,3,3-Trifluoro-1-(naphthalen-2-yl)propan-1-one (3r)^10a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 8.41 (s, 1H), 8.01–7.96 (m, 2H), 7.92–7.88 (m, 2H), 7.66–7.57 (m, 2H), 3.93 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 189.6, 136.0, 133.2, 132.3, 130.5, 129.7, 129.2, 128.9, 127.9, 127.2, 124.1 (q, J = 275.2 Hz), 123.4, 42.2 (q, J = 28.0 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −61.90.

3,3,3-Trifluoro-1-(thiophen-2-yl)propan-1-one (3s)^10d. Colorless liquid. ¹H NMR (400 MHz, CDCl₃) δ: 7.77–7.73 (m, 2H), 7.20–7.18 (m, 1H), 3.72 (q, J = 10.0 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 143.2, 135.7, 133.4, 128.5, 123.6 (q, J = 275.6 Hz), 43.0 (q, J = 28.6 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −61.93.

3,3,3-Trifluoro-2-methyl-1-phenylpropan-1-one (3t)^10a. Colorless liquid. ¹H NMR (400 MHz, CDCl₃) δ: 7.97–7.95 (m, 2H), 7.65–7.62 (m, 1H), 7.53–7.49 (m, 2H), 4.31–4.20 (m, 1H), 1.48 (d, J = 7.2 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 194.4, 135.6, 134.0, 129.0, 128.6, 125.3 (q, J = 278.3 Hz), 44.3 (q, J = 26.4 Hz), 11.7–11.6 (m). ¹⁹F NMR (376 MHz, CDCl₃) δ: −68.29.

2-(Trifluoromethyl)-3,4-dihydronaphthalen-1(2H)-one (3u)^10a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 8.05–8.03 (m, 1H), 7.35–7.31 (m, 1H), 7.28–7.26 (m, 1H), 3.30–3.07 (m, 3H), 2.53–2.20 (m, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 190.2, 143.1, 134.1, 131.9, 128.7, 127.8, 127.0, 125.0 (q, J = 278.1 Hz), 50.8 (q, J = 25.4 Hz), 27.5, 23.4–23.3 (m). ¹⁹F NMR (376 MHz, CDCl₃) δ: −67.53.

2-(Trifluoromethyl)-2,3-dihydro-1H-inden-1-one (3v)^10a. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 7.82–7.80 (m, 1H), 7.69–7.65 (m, 1H), 7.54–7.52 (m, 1H), 7.46–7.42 (m, 1H), 3.50–3.30 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 196.8, 152.0, 135.8, 129.1, 128.2, 126.5, 124.8 (q, J = 276.8 Hz), 124.7, 49.7 (q, J = 27.4 Hz), 27.6 (d, J = 2.3 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −67.76.

(3,3,3-Trifluoroprop-1-ene-1,1-diyl)dibenzene (5)¹⁷. White solid. ¹H NMR (400 MHz, CDCl₃) δ: 7.38–7.37 (m, 3H), 7.35–7.29 (m, 3H), 7.25–7.23 (m, 4H), 6.12 (q, J = 8.5 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃) δ: 152.5 (q, J = 5.6 Hz), 140.1, 137.3, 129.4, 129.1 (q, J = 1.7 Hz), 128.5, 128.0, 127.9, 123.1 (q, J = 270.0 Hz), 115.5 (q, J = 33.6 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ: −55.59.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We gratefully acknowledge the National Natural Science Foundation of China (21772062 and 21572078) for financial support of this work.

Notes and references

1. (a) C. Isanbora and D. O'Hagan, J. Fluorine Chem., 2006, 127, 303; (b) K. L. Kirk, Org. Process Res. Dev., 2008, 12, 305; (c) S. Purser, P. R. Moore, S. Swallow and V. Gouverneur, Chem. Soc. Rev., 2008, 37, 320; (d) W. K. Hagmann, J. Med. Chem., 2008, 51, 4359; (e) K. L. Kirk, Org. Process Res. Dev., 2008, 12, 305; (f) O. A. Tomashenko and V. V. Grushin, Chem. Rev., 2011, 111, 4475; (g) T. Furuya, A. S. Kamlet and T. Ritter, Nature, 2011, 473, 470; (h) P. S. Fier and J. F. Hartwig, J. Am. Chem. Soc., 2012, 134, 5524; (i) E. P. Gillis, K. J. Eastman, M. D. Hill, D. J. Donnelly and N. A. Meanwell, J. Med. Chem., 2015, 58, 8315.
2. (a) N. A. Meanwell, J. Med. Chem., 2011, 54, 2529; (b) M. Cametti, B. Crousse, P. Metrangolo, R. Milani and G. Resnati, Chem. Soc. Rev., 2012, 41, 31; (c) Y. Zhou, J. Wang, Z. Gu, S. Wang, W. Zhu, J. L. Aceña, V. A. Soloshonok, K. Izawa and H. Liu, Chem. Rev., 2016, 116, 422.
3. (a) R. Filler and L. M. Yagupolskii, Organofluorine Compounds in Medicinal Chemistry & Biomedical Applications, Elsevier, New York, 1993; (b) K. Müller, C. Faeh and F. Diederich, Science, 2007, 317, 1881; (c) J. Wang, M. Sanchez-Roselló, J. L. Aceña, C. Pozo, A. E. Sorochinsky, S. Fustero, V. A. Soloshonok and H. Liu, Chem. Rev., 2014, 114, 2432.
4. T. Hiyama, Organofluorine Compounds: Chemistry and Applications, Springer, Berlin, 2000.
5. R. E. Banks and C. J. Tatlow, Organofluorine Chemistry, Principles and Commercial Applications, Springer, New York, 1994.
6. (a) H. Song, Q. Han, C. Zhao and C. Zhang, Green Chem., 2018, 20, 1662; (b) W. Li, W. Xu, J. Xie, S. Yu and C. Zhu, Chem. Soc. Rev., 2018, 47, 654.
7. (a) Y. Itoh and K. Mikami, Org. Lett., 2005, 7, 4883; (b) Y. Itoh and K. Mikami, Tetrahedron, 2006, 62, 7199; (c) Y. Itoh and K. Mikami, J. Fluorine Chem., 2006, 127, 539; (d) V. Petrik and D. Cahard, Tetrahedron Lett., 2007, 48, 3327; (e) Y. Tomita, Y. Itoh and K. Mikami, Chem. Lett., 2008, 37, 1080; (f) T. Kino, Y. Nagase, Y. Ohtsuka, K. Yamamoto, D. Uraguchi, K. Tokuhisa and T. Yamakawa, J. Fluorine Chem., 2010, 131, 98; (g) P. V. Pham, D. A. Nagib and D. W. C. MacMillan, Angew. Chem., Int. Ed., 2011, 50, 6119; (h) N. Iqbal, S. Choi, E. Kim and E. J. Cho, J. Org. Chem., 2012, 77, 11383; (i) N. Iqbal, J. Jung, S. Park and E. J. Cho, Angew. Chem., Int. Ed., 2014, 53, 539.
8. (a) D. A. Nagib and D. W. C. MacMillan, Nature, 2011, 480, 224; (b) H. Jiang, Y. Cheng, Y. Zhang and S. Yu, Eur. J. Org. Chem., 2013, 5485; (c) S. W. Oh, Y. R. Malpani, N. Ha, Y.-S. Jung and S. B. Han, Org. Lett., 2014, 16, 1310; (d) D. B. Bagal, G. Kachkovskyi, M. Knorn, T. Rawner, B. M. Bhanage and O. Reiser, Angew. Chem., Int. Ed., 2015, 54, 6999.
9. (a) X. Liu, F. Xiong, X. Huang, L. Xu, P. Li and X. Wu, Angew. Chem., Int. Ed., 2013, 52, 6962; (b) R. Tomita, Y. Yasu, T. Koike and M. Akita, Angew. Chem., Int. Ed., 2014, 53, 7144; (c) L. Li, Q.-Y. Chen and Y. Guo, J. Org. Chem., 2014, 79, 5145.
10. (a) A. Deb, S. Manna, A. Modak, T. Patra, S. Maity and D. Maiti, Angew. Chem., Int. Ed., 2013, 52, 9747; (b) A. Maji, A. Hazra and D. Maiti, Org. Lett., 2014, 16, 4524; (c) Q. Lu, C. Liu, Z. Huang, Y. Ma, J. Zhang and A. Lei, Chem. Commun., 2014, 50, 14101; (d) Z. Hang, Z. Li and Z.-Q. Liu, Org. Lett., 2014, 16, 3648; (e) L. Zhang, Z. Li and Z.-Q. Liu, Org. Lett., 2014, 16, 3688; (f) Y. Yang, Y. Liu, Y. Jiang, Y. Zhang and D. A. Vicic, J. Org. Chem., 2015, 80, 6639; (g) X.-L. Yu, J.-R. Chen, D.-Z. Chen and W.-J. Xiao, Chem. Commun., 2016, 52, 8275; (h) L. Zhu, L.-S. Wang, B. Li, B. Fu, C.-P. Zhang and W. Li, Chem. Commun., 2016, 52, 6371; (i) L. Li, Xi. Mu, W. Liu, Y. Wang, Z. Mi and C.-J. Li, J. Am. Chem. Soc., 2016, 138, 5809; (j) H.-T. Qin, S.-W. Wu, J.-L. Liu and F. Liu, Chem. Commun., 2017, 53, 1696.
11. (a) Y. Yasu, T. Koike and M. Akita, Angew. Chem., Int. Ed., 2012, 51, 9567; (b) Y. Yasu, T. Koike and M. Akita, Org. Lett., 2013, 15, 2136; (c) S. Mizuta, S. Verhoog, K. M. Engle, T. Khotavivattana, M. O'Duill, K. Wheelhouse, G. Rassias, M. M′edebielle and V. Gouverneur, J. Am. Chem. Soc., 2013, 135, 2505; (d) J.-J. Dai, C. Fang, B. Xiao, J. Yi, J. Xu, Z.-J. Liu, X. Lu, L. Liu and Y. Fu, J. Am. Chem. Soc., 2013, 135, 8436; (e) Y. Yasu, Y. Arai, R. Tomita, T. Koike and M. Akita, Org. Lett., 2014, 16, 780.
12. (a) M. Oishi, H. Kondo and H. Amii, Chem. Commun., 2009, 1909; (b) Y. Wu, G. Lu, T. Yuan, Z. Xu, L. Wan and C. Cai, Chem. Commun., 2016, 52, 13668.
13. C.-P. Zhang, Z.-L. Wang, Q.-Y. Chen, C.-T. Zhang, Y.-C. Gu and J.-C. Xiao, Chem. Commun., 2011, 47, 6632.
14. (a) P. Novak, A. Lishchynskyi and V. V. Grushin, J. Am. Chem. Soc., 2012, 134, 16167; (b) Z. He, R. Zhang, M. Hu, L. Li, C. Ni and J. Hu, Chem. Sci., 2013, 4, 3478; (c) Y.-F. Wang, G. H. Lonca and S. Chiba, Angew. Chem., Int. Ed., 2014, 53, 1067; (d) I. Saidalimu, E. Tokunaga and N. Shibata, ACS Catal., 2015, 5, 4668; (e) X. Su, H. Huan, Y. Yuan and Y. Li, Angew. Chem., Int. Ed., 2017, 56, 1338; (f) T. Kawamoto, R. Sasaki and A. Kamimura, Angew. Chem., Int. Ed., 2017, 56, 1342; (g) B. Jiang, X. Zhang and C. Yang, Org. Chem. Front., 2018, 5, 1724.
15. (a) T. Umemoto and S. Ishihara, J. Am. Chem. Soc., 1993, 115, 2156; (b) T. Umemoto and K. Adachi, J. Org. Chem., 1994, 59, 5692; (c) J. C. Blazejewski, M. P. Wilmshurst, M. D. Popkin, C. Wakselman, G. Laurent, D. Nonclercq, A. Cleeren, Y. Ma, H. S. Seo and G. Leclercq, Bioorg. Med. Chem., 2003, 11, 335; (d) Y. Itoh and K. Mikami, Org. Lett., 2005, 7, 649; (e) K. Mikami, Y. Tomita, Y. Ichikawa, K. Amikura and Y. Itoh, Org. Lett., 2006, 8, 4671; (f) V. Petrik and D. Cahard, Tetrahedron Lett., 2007, 48, 3327; (g) K. Sato, T. Yuki, A. Tarui, M. Omote, I. Kumadaki and A. Ando, Tetrahedron Lett., 2008, 49, 3558; (h) K. Sato, M. Higashinagata, T. Yuki, A. Tarui, M. Omote, I. Kumadaki and A. Ando, J. Fluorine Chem., 2008, 129, 51; (i) K. Sato, T. Yuki, R. Yamaguchi, T. Hamano, A. Tarui, M. Omote, I. Kumadaki and A. Ando, J. Org. Chem., 2009, 74, 3815; (j) V. Matoušek, A. Togni, V. Bizet and D. Cahard, Org. Lett., 2011, 13, 5762.
16. (a) D. Ravelli, M. Fagnoni and A. Albini, Chem. Soc. Rev., 2013, 42, 97; (b) D. P. Hari and B. König, Angew. Chem., Int. Ed., 2013, 52, 4734; (c) C. K. Prier, D. A. Rankic and D. W. C. MacMillan, Chem. Rev., 2013, 113, 5322; (d) J. Xie, H. Jin and A. S. K. Hashmi, Chem. Soc. Rev., 2017, 46, 5193.
17. (a) H. Tan, H. Li, W. Ji and L. Wang, Angew. Chem., Int. Ed., 2015, 54, 8374; (b) W. Ji, H. Tan, M. Wang, P. Li and L. Wang, Chem. Commun., 2016, 52, 1462; (c) J. Xie, J. Li, T. Wurm, V. Weingand, H.-L. Sung, F. Rominger, M. Rudolph and A. S. K. Hashmi, Org. Chem. Front., 2016, 3, 841; (d) S. Yang, P. Li and L. Wang, Org. Lett., 2017, 19, 3386; (e) S. Yang, H. Tan, W. Ji, X. Zhang, P. Li and L. Wang, Adv. Synth. Catal., 2017, 359, 443; (f) L. Zhao, P. Li, X. Xie and L. Wang, Org. Chem. Front., 2018, 5, 1689; (g) W. Ji, P. Li, S. Yang and L. Wang, Chem. Commun., 2017, 53, 8482.
18. C. Shen, J. Xu, B. Ying and P. Zhang, ChemCatChem, 2016, 8, 3560.
19. H. Yi, C. Bian, X. Hu, L. Niu and A. Lei, Chem. Commun., 2015, 51, 14046.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c8qo01079j

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