Note pubs.acs.org/joc

Palladium-Catalyzed Decarboxylative Trifluoroethylation of Aryl Alkynyl Carboxylic Acids Jinil Hwang,† Kyungho Park,† Juseok Choe,† Hongkeun Min,† Kwang Ho Song,*,‡ and Sunwoo Lee*,† †

Department of Chemistry, Chonnam National University, Gwangju 500-757, Republic of Korea Department of Chemical & Biological Engineering, Korea University, Seoul 136-713, Republic of Korea

‡

S Supporting Information *

ABSTRACT: A trifluoroethylation of alkynes through a palladium-catalyzed decarboxylative coupling reaction was developed. When alkynyl carboxylic acids and ICH2CF3 were allowed to react with [Pd(η3-allyl)Cl]2/XantPhos and Cs2CO3 in N,N-dimethylformamide (DMF) at 80 °C for 1 h, the desired products were formed in good yields. This catalytic system showed high functional group tolerance. he introduction of fluorine and/or trifluoromethyl groups to organic compounds is a very important process to improve the physicochemical and bioactive properties of the compounds.1 According to recent reports, 20−30% of pharmaceutical and agrochemicals have fluorine and/or trifluoromethyl groups.2 A number of synthetic methods for fluorination and trifluoromethylation have been consistently reported; however, the number of reports on these methodologies has increased greatly in the past five years.3 The methods that have been studied even more are transitionmetal-catalyzed (or -mediated) fluorination4 and trifluoromethylation5 with commercially available fluorinating reagents or the development of efficient new fluorinating reagents. Metal fluorides and amine fluoride salts have been employed with nucleophilic and electrophilic fluorine sources, respectively.6 As trifluoromethyl sources, TMSCF3,7 TESCF3,8 ICF3,9 CF3CO2H,10 Togni’s reagent,11 Umemoto’s reagent,12 and Hartwig reagents13 have been used. Palladium, copper, gold, iron, and silver have been used as transition-metal sources.14 In addition, the use of trifluoroethylation to form bonds between sp2 or sp3 carbons and CH2CF3 have also been studied.15 Recently, the Xu group reported that the Sonogashira-type coupling reaction of terminal alkynes and ICH2CF3 afforded the corresponding trifluoroethylated alkynes in good yields.16 Although the Xu group suggested that this method has several advantages compared with the previous methods reported by Shibata,17 Ma,18 and Szabo19 independently, it has some drawbacks in that terminal alkynes also have to be prepared through multistep reactions, including Sonogashira coupling and a deprotection process. Instead of terminal alkynes, the use of alkynyl carboxylic acids as an alkyne source has several advantages. They are easily prepared from the coupling reaction of aryl halides and propiolic acid and are simply purified by using an acid and base workup process. In addition, they are stable for storage and easy handling.20 Since 2008, a variety of decarboxylative coupling reactions of alkynyl carboxylic acids have been developed by our group and others.21 In addition, a number of catalytic

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© 2014 American Chemical Society

decarboxylative couplings have been reported.22 However, decarboxylative coupling reactions with sp3 carbons are rare. Herein we report the decarboxylative coupling reaction of aryl alkynyl carboxylic acids with ICH2CF3 using palladium as the catalyst. To achieve our goal, a number of parameters were screened in the reaction of phenyl propiolic acid and ICH2CF3. The results are summarized in Table 1. Employment of the catalytic systems Pd(PPh3)Cl2/dppb/DMSO/(Cs2CO3 or DBU), which have been widely used in the decarboxylative coupling of aryl halides and aryl alkynyl carboxylic acids, did not produce satisfactory results (entries 1 and 2). When we used DABCO, which was chosen by Xu as the best base in the coupling of terminal alkynes and ICH2CF3, the desired product was formed in 30% yield (entry 3). The palladium source was changed to Pd2(dba)3, and a variety of ligands were screened. Sterically bulky monophosphines, such as tBuDavePhos, DavePhos, and XPhos showed yields of 5%, 9%, and 10%, respectively (entries 4−6). However, dppb and dppf, which are good ligands in the decarboxylative coupling of alkynyl carboxylic acids and aryl halides, did not give any desired product (entries 7 and 8). Chelating diphosphine ligands, such as DIOP, DPEPhos, and XantPhos, provided product in yields of 5%, 16%, and 27%, respectively (entries 9−11). With XantPhos as the ligand, the palladium source was screened. Pd(PPh3)Cl2 afforded the desired product in 81% yield (entry 12). Other palladium sources showed moderate yields (entries 13−15). To find the matched cases of palladium source and solvent, other solvents were tested. In the case of Pd(PPh3)2Cl2, all of the tested solvents, including as DMF, DMSO, and dioxane, gave unsatisfactory results (entries 16−18). When [Pd(η3-allyl)Cl]2 was employed as the palladium source, DMF showed better results than toluene did. This condition showed the best result (entry 19). DMSO provided a 28% yield of the product (entry 20). In the reaction with 1,4-dioxane, the desired product Received: February 11, 2014 Published: March 16, 2014 3267

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Note

Table 1. Optimization of the Conditions for the Trifluoroethylation of Alkynesa

Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

Catalyst Pd(PPh3)2Cl2 Pd(PPh3)2Cl2 Pd(PPh3)2Cl2 Pd2(dba)3 Pd2(dba)3 Pd2(dba)3 Pd2(dba)3 Pd2(dba)3 Pd2(dba)3 Pd2(dba)3 Pd2(dba)3 Pd(PPh3)2Cl2 [Pd(η3-allyl)Cl]2 Pd(OAc)2 Pd(CH3CN)2Cl2 Pd(PPh3)2Cl2 Pd(PPh3)2Cl2 Pd(PPh3)2Cl2 [Pd(η3-allyl)Cl]2 [Pd(η3-allyl)Cl]2 [Pd(η3-allyl)Cl]2

Ligand c

dppb dppb dppb tBuDavePhosd DavePhose XPhos f dppb dppf g DIOPh DPEPhosi XantPhos j XantPhos XantPhos XantPhos XantPhos XantPhos XantPhos XantPhos XantPhos XantPhos Xantphos

Base

Solvent

Yield (%)b

Cs2CO3 DBU DABCO Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3

DMSO DMSO DMSO toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene DMF DMSO 1,4-dioxane DMF DMSO 1,4-dioxane

10 trace 30 5 9 10 trace trace 5 16 27 81 56 35 44 24 44 42 87 28 66

a

Reaction conditions: 1a (0.6 mmol), ICH2CF3 (0.3 mmol), Pd (0.03 mmol), ligand (0.03 mmol), and base (0.3 mmol) were reacted in the solvent (1.0 mL) at 80 °C for 1 h. bYields were determined by 19F NMR spectroscopy and gas chromatography with an internal standard. c1,4Bis(diphenylphosphino)butane. d2′-(Di-tert-butylphosphino)-N,N-dimethylbiphenyl-2-amine. e2-Dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl. f2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl. g1,1′-Bis(diphenylphosphino)ferrocene. h2,3-O-isopropylidene-2,3-dihydroxy-1,4bis(diphenylphosphino)butane. iBis[(2-diphenylphosphino)phenyl] ether. j4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene.

was formed in 66% yield (entry 21). In all cases, the esterification product, 2,2,2-trifluoroethyl 3-phenylpropioate, was not found in the reaction mixture under these optimized conditions. To test the substrate scope, the optimized conditions were employed in the decarboxylative coupling reaction of a variety of aryl alkynyl carboxylic acids. The results are summarized in Table 2. All of the starting materials were prepared by the coupling reactions of propiolic acid with aryl iodides or bromides. Phenylpropiolic acid afforded (4,4,4-trifluorobut-1ynyl)benzene in 87% yield based on 19F NMR analysis (entry 1). However, we failed to obtain it with purity because of its high volatility. Alkyl-substituted aryl alkynyl carboxylic acids 1b−e provided the corresponding trifluoroethylated products in yields of 85%, 65%, 77%, and 83%, respectively (entries 2−5). Methoxy-substituted substrates 1f and 1g showed yields of 89% and 61%, respectively (entries 6 and 7). Substrates bearing electron-withdrawing functional groups, such as ketone, ester, and nitrile, exhibited moderate yields in the coupling reaction (entries 8−10). 1-Naphthyl and 4′-biphenyl alkynyl carboxylic acids afforded the corresponding coupled products in yields of 88% and 64%, respectively (entries 11 and 12). Fluorosubstituted substrate 1m provided the desired product in moderate yield (entry 13). Thiophene-substituted alkynyl carboxylic acid 1n also produced the trifluoroethylated product in 45% yield (entry 14). To expand this methodology to the one-pot synthesis of trifluorobutynyl arenes from propiolic acid, we investigated the optimized conditions for sequential Sonogashira coupling of aryl

iodides with propiolic acid and decarboxylative coupling with ICH2CF3. Among the tested conditions in Table 1, the conditions showing the best yield were first employed in the reaction of phenyl iodide and propiolic acid, and then ICH2CF3 was added to the reaction mixture. The results are summarized in Table 3. With XantPhos and Cs2CO3, palladium sources, such as Pd(PPh3)2Cl2 and [Pd(η3-allyl)Cl]2, and solvents were tested. When Pd(PPh3)2Cl2 was employed in toluene or DMSO, the desired product was not formed (entries 1 and 2). In 1,4-dioxane solvent, the yield of product was 17% (entry 3). Changing the palladium source to [Pd(η3-allyl)Cl]2 afforded the desired product in yields of 45% and 12% in DMF and 1,4-dioxane, respectively (entries 4 and 5). Under these conditions, when 4-iodotoluene and 2-iodoanisole were employed, the desired coupling products were formed in yields of 43% and 39%, respectively (entries 6 and 7). To understand the reactivity of ICH2CF3 in this decarboxylative coupling, competitive reactions were carried out, as shown in Table 4. The decarboxylative coupling reaction with ICH2CF3 showed lower reactivity than those with phenyl iodide and bromide. However, it showed a higher reactivity than phenyl chloride did. On the basis of these results, the order of the reactivity toward decarboxylative coupling is as follows: PhI > PhBr > ICH2CF3 ≫ PhCl. In summary, we have developed a synthesis of trifluoroethylated alkynes from the palladium-catalyzed decarboxylative coupling of aryl alkynyl carboxylic acids with ICH2CF3. The use of aryl alkynyl carboxylic acids has several advantages, including simple preparation. The optimized conditions were 3268

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Table 2. Trifluoroethylation of Aryl Alkynyl Carboxylic Acidsa

a

Reaction conditions: 1 (6.0 mmol), ICH2CF3 (3.0 mmol), [Pd(η3-allyl)Cl]2 (0.15 mmol), XantPhos (0.3 mmol), and Cs2CO3 (3.0 mmol) were reacted in DMF (10.0 mL) at 80 °C for 1 h. bIsolated yields are averages of at least two runs. cYields were determined by 19F NMR spectroscopy with an internal standard.

Table 3. One-Pot Synthesis of Trifluorobut-1-ynyl Arenes from Propiolic Acida

Entry

Ar

Catalyst

Solvent

Product

Yield (%)

1 2 3 4 5 6 7

C6H5 C6H5 C6H5 C6H5 C6H5 4-MeC6H4 2-MeOC6H4

Pd(PPh3)2Cl2 Pd(PPh3)2Cl2 Pd(PPh3)2Cl2 [Pd(η3-allyl)Cl]2 [Pd(η3-allyl)Cl]2 [Pd(η3-allyl)Cl]2 [Pd(η3-allyl)Cl]2

toluene DMSO 1,4-dioxane DMF 1,4-dioxane DMF DMF

− − 2a 2a 2a 2d 2f

− − 17 45 12 43 39

a

Reaction conditions: ArI (6.0 mmol), propiolic acid (12.0 mmol), Pd (1.2 mmol), XantPhos (1.2 mmol), and Cs2CO3 (24.0 mmol) were reacted in the solvent (20.0 mL) at 50 °C for 5 h, and then ICH2CF3 (3.0 mmol) was added and reacted at 80 °C for 1 h.

functional groups such as ketone, ester, nitrile, and fluoro groups. Furthermore, the desired trifluoroethylated alkynyl compounds could be obtained from propiolic acid using a one-pot sequential Sonogashira coupling and decarboxylative coupling reaction.

such that the substrates were reacted with [Pd(η3-allyl)Cl]2/ XantPhos and Cs2CO3 in DMF at 80 °C for 1 h. This catalytic system provided shorter reaction times and showed a broad substrate scope. In addition, it exhibited high tolerance toward 3269

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The Journal of Organic Chemistry

Note

F NMR (282 MHz, CDCl3) δ −67.06 (t, J = 9.6 Hz); HRMS (ESI, TOF) calcd for C12H12F3 [M + H]+ 213.0891, found 213.0891. 1-Methoxy-2-(4,4,4-trifluorobut-1-ynyl)benzene (2f). 3-(2Methoxyphenyl)propiolic acid (1f) (1.06 g) afforded the product 2f (571.9 mg, 2.66 mmol, 89%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.46 (dd, J = 7.6, 1.7 Hz, 1H), 7.38−7.29 (m, 1H), 6.92 (dd, J = 16.9, 8.3 Hz, 2H), 3.88 (s, 3H), 3.36 (q, J = 9.6 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 160.6, 134.1, 130.4, 124.6 (q, J = 275 Hz), 120.7, 111.6, 110.9, 81.7 (q, J = 5.1 Hz), 81.0, 55.9, 27.2 (q, J = 34.5 Hz); 19 F NMR (282 MHz, CDCl3) δ −66.83 (t, J = 9.6 Hz); HRMS (ESI, TOF) calcd for C11H10OF3 [M + H]+ 215.0684, found 215.0680. 1,2,3-Trimethoxy-5-(4,4,4-trifluorobut-1-ynyl)benzene (2g). 3-(3,4,5-Trimethoxyphenyl)propiolic acid (1g) (1.42 g) afforded the product 2g (501.9 mg, 1.83 mmol, 61%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 6.68 (s, 2H), 3.85 (s, 12H), 3.27 (q, J = 9.6 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 133.0, 139.1, 124.1 (q, J = 275.1 Hz), 117.1, 109.0, 84.3, 60.9, 56.1, 26.7 (q, J = 34.5 Hz); 19F NMR (282 MHz, CDCl3) δ −66.81 (t, J = 9.6 Hz); HRMS (ESI, TOF) calcd for C13H14O3F3 [M + H]+ 275.0895, found 275.0897. 1-(4-(4,4,4-Trifluorobut-1-ynyl)phenyl)ethanone (2h).16 3-(4Acetylphenyl)propiolic acid (1h) (1.13 g) afforded the product 2h (441.1 mg, 1.95 mmol, 65%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.90 (d, J = 8.6 Hz, 2H), 7.52 (d, J = 8.5 Hz, 2H), 3.31 (q, J = 9.5 Hz, 2H), 2.59 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 197.2, 136.6, 131.9, 128.1, 126.8, 124.0 (q, J = 275 Hz), 83.5, 80.8 (q, J = 5.2 Hz), 26.7 (q, J = 35 Hz), 26.5; 19F NMR (282 MHz, CDCl3) δ −66.68 (t, J = 9.5 Hz); MS m/z (relative intensity) 226 (34), 211 (100), 182 (12), 163 (18), 133 (52), 107 (11), 88 (8). Methyl 4-(4,4,4-Trifluorobut-1-ynyl)benzoate (2i).16 3-(4(Methoxycarbonyl)phenyl)propiolic acid (1i) (1.23 g) afforded the product 2i (450.5 mg, 1.86 mmol, 62%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.98 (d, J = 8.7 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H), 3.91 (s, 3H), 3.30 (q, J = 9.5 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 166.3, 131.7, 130.0, 129.4, 126.7, 124.0 (q, J = 275 Hz), 83.5, 80.5 (q, J = 5 Hz), 52.1, 26.7 (q, J = 34.7 Hz); 19F NMR (282 MHz, CDCl3) δ −66.75 (t, J = 9.5 Hz); MS m/z (relative intensity) 242 (50), 211 (100), 182 (12), 163 (11), 133 (48). 4-(4,4,4-Trifluorobut-1-ynyl)benzonitrile (2j). 16 3-(4Cyanophenyl)propiolic acid (1j) (1.03 g) afforded the product 2j (395.3 mg, 1.89 mmol, 63%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.66−7.57 (m, 2H), 7.57−7.49 (m, 2H), 3.31 (q, J = 9.4 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 132.4, 132.0, 127.0, 123.9 (q, J = 275 Hz), 118.2, 112.2, 82.8, 82.1 (q, J = 5 Hz), 26.9 (q, J = 34.8 Hz); 19 F NMR (282 MHz, CDCl3) δ −66.54 (t, J = 9.4 Hz); MS m/z (relative intensity) 209 (52), 189 (18), 140 (100), 113 (28), 63 (18). 1-(4,4,4-Trifluorobut-1-ynyl)naphthalene (2k).18 3-(Naphthalen1-yl)propiolic acid (1k) (1.18 g) afforded the product 2k (618.3 mg, 2.64 mmol, 88%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.28 (d, J = 8.3 Hz, 1H), 7.77 (dd, J = 7.8, 4.3 Hz, 2H), 7.64 (d, J = 7.1 Hz, 1H), 7.54 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H), 7.46 (ddd, J = 8.1, 6.9, 1.4 Hz, 1H), 7.34 (dd, J = 8.3, 7.2 Hz, 1H), 3.36 (q, J = 9.5 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 133.4, 133.1, 130.8, 129.2, 128.3, 126.9, 126.4, 125.8, 125.0, 124.3 (q, J = 275 Hz), 119.7, 82.6, 82.3 (q, J = 5 Hz), 27.0 (q, J = 34.5 Hz); 19F NMR (282 MHz, CDCl3) δ −66.60 (t, J = 9.6 Hz); MS m/z (relative intensity) 234 (100), 165 (88), 139 (8), 82 (9), 63 (7). 4-(4,4,4-Trifluorobut-1-ynyl)biphenyl (2l).16 3-(Biphenyl-4-yl)propiolic acid (1l) (1.33 g) afforded the product 2l (499.7 mg, 1.92 mmol, 64%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.61− 7.49 (m, 6H), 7.48−7.40 (m, 2H), 7.39−7.32 (m, 1H), 3.29 (q, J = 9.6 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 141.5, 140.2, 132.2, 128.9, 127.7, 127.02, 126.98, 124.2 (q, J = 275.1 Hz), 121.0, 84.2, 78.1 (q, J = 5.1 Hz), 26.9 (q, J = 34.6 Hz); 19F NMR (282 MHz, CDCl3) δ −66.80 (t, J = 9.6 Hz); MS m/z (relative intensity) 260 (100), 191 (67), 165 (10), 94 (12), 82 (8). 1-Fluoro-4-(4,4,4-trifluorobut-1-ynyl)benzene (2m).18 3-(4Fluorophenyl)propiolic acid (1m) (984.8 mg) afforded the product 2m (339.6 mg, 1.68 mmol, 56%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.52−7.33 (m, 2H), 7.08−6.92 (m, 2H), 3.24 (q, J = 9.6 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 162.8 (d, J = 248 Hz), 133.8 (d, J = 8.4 Hz), 124.2 (q, J = 275 Hz), 118.3 (d, J = 3.5 Hz), 115.6 19

Table 4. Competitive Reactions of ICH2CF3 and Phenyl Halides

Yields (%)

■

Entry

X

2a

3a

1 2 3

I Br Cl

trace 12 56

83 72 trace

EXPERIMENTAL SECTION

General Procedure for the Synthesis of 2,2,2-Trifluoroethylated Alkynes. Aryl alkynyl carboxylic acid (6.0 mmol), ICH2CF3 (630 mg, 3.0 mmol), [Pd(η3-allyl)Cl]2 (54.9 mg, 0.15 mmol), XantPhos (173.6 mg, 0.3 mmol), Cs2CO3 (977.5 mg, 3.0 mmol), and DMF (10 mL) were added to a one-neck flask. The flask was sealed, and the reaction mixture was allowed to stir at 80 °C for 1 h. The mixture was then poured into water and extracted with Et2O (3 × 20 mL). The combined ethyl acetate extracts were dried over MgSO4 and passed through Celite. The solvent was removed under vacuum, and the resulting crude product was purified by flash chromatography on silica gel. The products 2a−f, 2i, and 2k−n were eluted with pentane, and 2g, 2h, and 2j were eluted with 1:4 ethyl acetate/hexane. (4,4,4-Trifluorobut-1-ynyl)benzene (2a).18 Phenylpropiolic acid (1a) (876.8 mg) afforded the product 2a (480.7 mg, 2.61 mmol, 87%) as a colorless oil. 19F NMR (282 MHz, CDCl3) δ −66.83 (t, J = 9.6 Hz); MS m/z (relative intensity) 184 (58), 164 (12), 133 (10), 115 (100), 89 (18). 1-Methyl-2-(4,4,4-trifluorobut-1-ynyl)benzene (2b).23 3-oTolylpropiolic acid (1b) (961.0 mg) afforded the product 2b (505.4 mg, 2.55 mmol, 85%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.40 (d, J = 7.5 Hz, 1H), 7.25−7.09 (m, 3H), 3.31 (q, J = 9.5 Hz, 2H), 2.42 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 140.6, 132.0, 129.4, 128.6, 125.5, 124.3 (q, J = 275 Hz), 121.9, 83.3, 81.3 (q, J = 5 Hz), 26.9 (q, J = 34.5 Hz), 20.5; 19F NMR (282 MHz, CDCl3) δ −66.98 (t, J = 9.5 Hz); MS m/z (relative intensity) 198 (69), 129 (100), 115 (23), 77 (15), 51 (19). 1-Methyl-3-(4,4,4-trifluorobut-1-ynyl)benzene (2c).23 3-mTolylpropiolic acid (1c) (961.0 mg) afforded the product 2c (386.5 mg, 1.95 mmol, 65%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.31−7.24 (m, 2H), 7.18−7.11 (m, 2H), 3.20 (q, J = 9.6 Hz, 2H), 2.28 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 138.0, 132.4, 129.6, 128.9, 128.2, 124.3 (q, J = 275 Hz), 122.1, 84.5, 77.1 (q, J = 5 Hz), 26.6 (q, J = 34.5 Hz), 21.0; 19F NMR (282 MHz, CDCl3) δ −66.92 (t, J = 9.6 Hz); MS m/z (relative intensity) 198 (83), 183 (12), 129 (100), 102 (8), 77 (9), 63 (11). 1-Methyl-4-(4,4,4-trifluorobut-1-ynyl)benzene (2d).18 3-pTolylpropiolic acid (1d) (961.0 mg) afforded the product 2d (457.8 mg, 2.31 mmol, 77%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.32 (d, J = 8.1 Hz, 2H), 7.09 (d, J = 7.2 Hz, 2H), 3.22 (q, J = 9.6 Hz, 2H), 2.32 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 138.8, 131.7, 129.0, 124.3 (q, J = 275 Hz), 119.1, 84.4, 76.7 (q, J = 5 Hz), 26.7 (q, J = 34.5 Hz), 21.3; 19F NMR (282 MHz, CDCl3) δ −66.95 (t, J = 9.6 Hz); MS m/z (relative intensity) 198 (69), 183 (10), 129 (100), 102 (6), 77 (10). 2,4-Dimethyl-1-(4,4,4-trifluorobut-1-ynyl)benzene (2e). 3(2,4-Dimethylphenyl)propiolic acid (1e) (1.05 g) afforded the product 2e (528.4 mg, 2.49 mmol, 83%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.28 (d, J = 7.8 Hz, 1H), 7.00 (s, 1H), 6.92 (d, 7.8 Hz, 1H), 3.27 (q, J = 9.6 Hz, 2H), 2.37 (s, 3H), 2.29 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 140.4, 138.7, 131.9, 130.3, 127.6 (q, J = 275 Hz), 126.3, 118.9, 83.4, 80.5 (q, J = 5 Hz), 26.9 (q, J = 34.5 Hz), 21.3, 20.3; 3270

dx.doi.org/10.1021/jo5003032 | J. Org. Chem. 2014, 79, 3267−3271

The Journal of Organic Chemistry

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(d, J = 22 Hz), 83.3, 77.3 (q, J = 5 Hz), 26.7 (q, J = 34.6 Hz); 19F NMR (282 MHz, CDCl3) δ −66.88 (t, J = 9.6 Hz); MS m/z (relative intensity) 202 (43), 182 (6), 151 (4), 133 (100), 83 (11). 2-(4,4,4-Trifluorobut-1-ynyl)thiophene (2n). 3-(Thiophen-2yl)propiolic acid (1n) (913.0 mg) afforded the product 2n (256.8 mg, 1.35 mmol, 45%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.29−7.22 (m, 2H), 6.97 (dd, J = 5.1, 3.7 Hz, 1H), 3.29 (q, J = 9.6 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 130.0, 132.5, 127.2 (t, J = 41 Hz), 124.0 (q, J = 275 Hz), 122.0, 81.4 (q, J = 4.5 Hz), 77.7, 27.0 (q, J = 34.7 Hz); 19F NMR (282 MHz, CDCl3) δ −66.66 (t, J = 9.5 Hz); HRMS (ESI, TOF) calcd for C8H6F3S [M + H]+ 191.0142, found 191.0146.

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ASSOCIATED CONTENT

S Supporting Information *

Copies of 1H and 13C{1H} NMR spectra for all products. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (K.H.S.). *E-mail: [email protected] (S.L.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This research was supported by the Nano-Material Technology Development Program through the National Research Foundation (NRF) of Korea, funded by the Ministry of Education, Science and Technology (Grant 2012M3A7B4049655). Spectral data were obtained from the Korea Basic Science Institute, Gwangju Branch.

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REFERENCES

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dx.doi.org/10.1021/jo5003032 | J. Org. Chem. 2014, 79, 3267−3271