HETEROCYCLES

Paper | Special issue | Vol. 88, No. 2, 2014, pp. 1201-1212
Received, 4th July, 2013, Accepted, 26th September, 2013, Published online, 4th October, 2013.
DOI: 10.3987/COM-13-S(S)84

■ Polyfluoroalkylation of Carbonyl Compounds by Polyfluoroalkyl Anions Generated from Polyfluorcarboxamides

Natshumi Wakita and Shoji Hara*

Graduate School of Engineering, Hokkaido University, Kita 13 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-8628, Japan

Abstract

Polyfluoroalkyl anions, generated by reduction of (polyfluoroalkanoyl)piperidines with Et3BHK, were used for the polyfluoroalkylation of carbonyl compounds. Trifluoromethylation of aromatic aldehydes proceeded in good yields, and that of aliphatic aldehydes afforded a moderate yield. In contrast, the yield was low when the reaction involved benzophenone. Pentafluoroethylation and octafluorobutylation of aldehydes were also carried out by using the corresponding (polyfluoroalkanoyl)piperidines, which were prepared from commercially available polyfluorocompounds. The (polyfluoroalkanoyl)piperidines were also prepared through polyfluorination, and were used in the polyfluoroalkylation of aldehydes.

INTRODUCTION
Nucleophilic trifluoromethylation of carbonyl compounds has been widely performed to introduce a trifluoromethyl group into the substrate.1 The trifluoromethyl anion is unstable. Therefore, it is generated from the precursor in the presence of an electrophile such as a carbonyl compound. Although a number of various trifluoromethyl compounds have been used as precursors, trifluoromethyltrimethylsilane has been most frequently used and is well-studied.1c,1d,2
Recently, trifluoroacetaldehyde hemiaminals (1) have attracted much attention as an accessible trifluoromethyl source, because they can be prepared from economical materials such as fluoroform1j,3 and trifluoroacetaldehyde hemiacetal.1j,4 They are converted to their metal salts (2) to generate the trifluoromethyl anion.5 We can obtain 2 by the reduction of trifluoroacetamide (3).6 Moreover, various (polyfluoroalkanoyl)amides are obtainable from either commercially available polyfluorocompounds or through polyfluorination reactions, and they can be used as a source for polyfluoroalkyl anions (Scheme 1).

RESULTS AND DISCUSSION
Trifluoromethylation of benzaldehyde was carried out using N-(trifluoroacetyl)piperidine, N-(trifluoroacetyl)pyrrolidine, and N,N-diethyltrifluoroacetamide as trifluoromethyl anion sources, and potassium triethylborohydride, DIBAH and potassium triisopropoxyborohydride as reducing reagents under various conditions (Table 1). A reducing reagent and benzaldehyde were successively added to the amide in THF at -78 °C (Entries 1—5) or at room temperature (Entry 6), and the resulting mixture was stirred for 24 h at 50 °C. Maintaining an interval between each addition of the reagents did not improve the results. The expected trifluoromethylated product (2a) was formed, only when N-(trifluoroacetyl)piperidine or N-(trifluoroacetyl)pyrrolidine was treated with potassium triethylborohydride (Entries 1, 4, and 6). The best yield was obtained by adding potassium triethylborohydride and benzaldehyde to N-(trifluoroacetyl)piperidine at room temperature (Entry 6).

The present trifluoromethylation reaction was applied to various carbonyl compounds. In the reaction with aromatic aldehydes and cinnamaldehyde, the corresponding trifluoromethylated products were obtained in good yield (Entries 1-5 in Table 2). From adamantane-1-carbaldehyde that has no α-proton, the trifluoromethylated product was obtained in 60% yield (Entry 6). In contrast, the reaction with cyclohexanecarbaldehyde that has α-proton, afforded an aldol reaction product as the main product. However, when the reaction was carried out in CH2Cl2 instead of THF, the trifluoromethylated product was obtained in 45% yield (Entry 7). In the reaction with benzophenone, most of the starting material remained unchanged (Entry 8).

As various (polyfluoroalkanoyl)piperidines are obtainable from commercially available polyfluoro- compounds, the present method is applicable to the various polyfluoroalkylation of carbonyl compounds. For example, N-(pentafluoropropanoyl)piperidine (1b) was prepared from methyl pentafluoropropionate7 and was used for the pentafluoroethylation of 1-naphthaldehyde. The reaction proceeded similar to trifluoromethylation, and the pentafluoroethylated product (2i) was obtained in high yield. N-(2,2,3,3,4,4,5,5-Octafluoropetanoyl)piperidine (1c) was prepared from commercially available 2,2,3,3,4,4,5,5-octafluoropentanol in three steps7-9 and was used in the reaction with 1-naphthaldehyde. The reaction of 1c with aldehyde was sluggish and the octafluorobutylated product 2j was formed in poor yield under the trifluoromethylation conditions. However, 2j was obtained in 61% yield by carrying the reaction at 40 °C for 24 h using 4 equivalents of 1c and KBEt3H to 1-naphthaldehyde without solvent (Scheme 2).

(Polyfluoroalkanoyl)piperidines can be also prepared through polyfluorination reactions. For example, methyl 2-(arylsulfanyl)-2,2-difluoroacetate (3) was prepared by difluorination of methyl 2-(arylsulfanyl)acetate using IF5-Et3N-3HF,10 and then converted to N-2-(arylsulfanyl)-2,2-difluoroacetylpiperidine (4).7 The reaction of 4 with an aldehyde was performed as in the case of 2a, and the (arylsulfanyl)difluoromethylated product (5) was obtained in high yield (Scheme 3).

Methyl 2,2,3,3-tetrafluoro-3-phenylpropionate (7) was prepared from methyl 2-(arylsulfanyl)propionate in 74% yield by using our recently developed method,11 and the resulting 7 was converted to the amide (8).7 Although the reaction of 8 with aldehyde was sluggish, the expected polyfluoroalkylated product (9) was obtained in 60% yield by performing the reaction at 40 °C for 24 h using 4 equivalents of 8 and KEt3BH to the aldehyde (Scheme 4).

EXPERIMENTAL
4.1. General
The melting points were measured with a Yanagimoto micro melting-point apparatus. The IR spectra were recorded using a JASCO FT/IR-410. The 1H NMR (400 MHz) spectra, 19F NMR (376 MHz) spectra, and 13C NMR (100 MHz) were recorded in CDCl3 on a JEOL JNM-A400II FT NMR and the chemical shift, δ, is referred to TMS (1H, 13C) and CFCl3 (19F), respectively. The EI-high-resolution mass spectra were measured on a JEOL JMS-700TZ. KBEt3H (1.0 M in THF) was purchased from Aldrich Chemica and KB(OPri)3H was prepared from B(OPri)3 and KH according to the literature.12 IF5 in a stainless-steel cylinder was supplied by Asahi Glass Co., Ltd. IF5 was transferred through a TeflonTM tube into a TeflonTM FEP bottle from the cylinder under an N2 atmosphere. IF5 was transferred quickly from the bottle to the reaction vessel made of TeflonTM FEP in open air. IF5 decomposes in air emitting HF fume, and, therefore, it should be carefully handled in a bench hood with rubber-gloved hands.11 2,2,3,3,4,4,5,5-Octafluoropentanol was donated from Daikin Industries, Ltd.
4.2. Preparation of N-(polyfluoroalkanoyl)piperidine
N-(Polyfluoroalkanoyl)piperidines were prepared from the corresponding ethyl or methyl polyfluoroalkanoate with piperidine according to the literature.7
4.2.1. N-(Trifluoroacetyl)piperidine (1a)
IR (neat) 2945, 1691, 1193, 1128 cm-1. 1H NMR (400MHz, CDCl3) δ 1.65-1.71 (6H, m), 3.54-3.63 (4H, m). 13C NMR (100MHz, CDCl3) δ 23.8, 25.1, 26.0, 44.2, 46.5 (t, 4JC-F = 3.5 Hz), 116.4 (t, 1JC-F = 287.8 Hz), 154.9 (t, 2JC-F = 35.3 Hz). 19F NMR (373MHz, CDCl3) δ -69.49 (3F, s) (lit.13 -68.02).
4.2.2. N-(2,2,3,3,3-Pentafluoropropanoyl)piperidine (1b)
IR (neat) 2947, 1684, 1175 cm-1. 1H NMR (400MHz, CDCl3) δ 1.64-1.71 (6H, m), 3.61 (4H, brs). 13C NMR (100MHz, CDCl3) δ 23.7, 25.0, 26.0, 44.0, 46.2, 108.3 (tq, 1JC-F = 270.6 Hz, 2JC-F = 36.0 Hz), 117.9 (tq, 2JC-F = 34.4 Hz, 1JC-F = 285.6 Hz), 155.6 (t, 2JC-F = 24.8 Hz). 19F NMR (373MHz, CDCl3) δ -82.77 (3F, s), -115.44 (2F, s). HRMS (EI) calcd for C8H10F5NO (M+) 231.06825, found 231.06888.
4.2.3. N-(2,2,3,3,4,4,5,5-Octafluoropentanoyl)piperidine (1c)
Ethyl 2,2,3,3,4,4,5,5-octafluoropentanoate was prepared from 2,2,3,3,4,4,5,5-octafluoropentanol according to the literature,8,9 and then converted to 1c according to the literature.7
IR (neat) 2950, 1682, 1450, 1166 cm-1. 1H NMR (400MHz, CDCl3) δ 1.65-1.71 (6H, m), 3.61-3.63 (4H, m), 6.33 (1H, tt, J = 52.3, 5.7 Hz). 13C NMR (100MHz, CDCl3) δ 23.7, 25.1, 26.0, 44.5, 46.5 (t, 4JC-F = 6.3 Hz), 105.0-114.1 (4C, m), 156.3 (t, 2JC-F = 24.6 Hz). 19F NMR (373MHz, CDCl3) δ -112.13 (2F, t, J = 9.0 Hz), -124.50 to -124.56 (2F, m), -129.02 to -129.12 (2F, m), -138.17 (2F, dm, J = 52.0 Hz). HRMS (EI) calcd for C10H11F8NO (M+) 313.07129, found 313.07058.
4.2.4. N-2-{(4-Chlorophenyl)sulfanyl}-2,2-difluoroacetylpiperidine (4)
Methyl 2-{(4-chlorophenyl)sulfanyl}-2,2-difluoroacetate (3) was prepared from methyl 2-{(4-chlorophenyl)sulfanyl}acetate according to the literature,10 and converted to 4 according to the literature.7 White solid. Mp 77-79 °C. IR (KBr) 2935, 1671, 1038 cm-1. 1H NMR (400MHz, CDCl3) δ 1.62-1.69 (6H, m), 3.60-3.64 (4H, m), 7.37 (2H, d, J = 8.3 Hz), 7.56 (2H, d, J = 8.3 Hz). 13C NMR (100MHz, CDCl3) δ 24.2, 25.5, 26.3, 44.8, 47.0 (t, 4JC-F = 5.0 Hz), 124.2, 124.6 (t, 1JC-F = 291.4 Hz), 129.2 (2C), 136.8, 137.9 (2C), 159.2 (t, 2JC-F = 26.2 Hz). 19F NMR (373MHz, CDCl3) δ -73.52 (2F, s). HRMS (EI) calcd for C13H14Cl F2NOS (M+) 305.04494, found 305.04527.
4.2.5. N-(2,2,3,3-Tetrafluoro-3-phenylpopanoyl)piperidine (8)
Methyl 3-phenyl-2,2,3,3-tetrafluoropropionate (7) was prepared from methyl 2-{(4-chlorophenyl)sulfanyl}propionate in three steps according to the literature,11 and converted to 8 by the reaction with piperidine.7 IR (neat) 2941, 1675, 1452, 1294, 1120 cm-1. 1H NMR (400MHz, CDCl3) δ 1.63-1.68 (6H, m), 3.59-3.64 (4H, m), 7.45-7.52 (3H, m), 7.62 (2H, d, J = 7.5 Hz). 13C NMR (100MHz, CDCl3) δ 24.2, 25.5, 26.4, 44.8, 46.9-47.1 (m), 111.6 (tt, 1JC-F = 264.6 Hz, 2JC-F = 37.4 Hz), 116.1 (tt, 1JC-F = 253.5 Hz, 2JC-F = 31.5 Hz) , 126.8 (tt, 3JC-F = 6.5 Hz, 4JC-F = 1.5 Hz), 128.1 (2C), 130.3 (t, 2JC-F = 24.3 Hz), 131.1 (2C, t, 4JC-F = 1.7 Hz), 157.7 (t, 2JC-F =26.0 Hz). 19F NMR (373MHz, CDCl3) δ -110.91 (2F, s), -111.62 (2F, s). HRMS (EI) calcd for C14H15F4NO (M+) 289.10898, found 289.10820.
4.3. Perfluoroalkylation of carbonyl compounds
4,3,1. 2,2,2-Trifluoro-1-phenylethanol (2a)
To a THF solution (3 mL) of 1a (181 mg, 1 mmol) were added a 1.0 M THF solution of Et3BHK (1 mL, 1 mmol) and benzaldehyde (53 mg, 0.5 mmol) successively at room temperature under N2 atmosphere. The mixture was stirred at 50 °C for 24 h and then 30% aqueous H2O2 (2 mL) was added at 0 °C. After stirring for 1 h, the mixture was extracted with Et2O (30 mL X 3). The combined organic phase was dried over MgSO4 and the yield of 2a was determined by 19F NMR using fluorobenzene as internal standard (99%). Pure 2a was obtained by column chromatography (silica gel/CH2Cl2:hexane = 4:1). IR (neat) 3397, 1267, 1127 cm-1. 1H NMR (400MHz, CDCl3) δ 5.01-5.06 (1H, m), 7.41-7.49 (5H, m). 13C NMR (100MHz, CDCl3) δ 72.8 (q, 2JC-F = 31.9 Hz), 124.3 (q, 1JC-F = 282.3 Hz), 127.4, 128.6 (2C), 129.6 (2C), 133.9 (q, 3JC-F = 0.9 Hz). 19F NMR (373MHz, CDCl3) δ -78.99 (3F, d, J = 7.1 Hz) {lit.14 -78.77 (d, J = 7.6 Hz)}.
4,2,2. 1-(4-Bromophenyl)-2,2,2-trifluoroethanol (2b)
IR (neat) 3397, 1492, 1268, 1173, 1130 cm-1. 1H NMR (400MHz, CDCl3) δ 4.98-5.03 (1H, m), 7.35-7.44 (2H, m), 7.54-7.56 (2H, m). 13C NMR (100MHz, CDCl3) δ 72.2 (q, 2JC-F = 32.2 Hz), 123.8, 123.9 (q, 1JC-F = 282.1 Hz), 129.0 (2C), 131.8 (2C), 132.7. 19F NMR (373MHz, CDCl3) δ -79.15 (3F, d, J = 7.1 Hz) {lit.14 -78.94 (d, J = 6.8 Hz)}.
4,2,3. (E)-1,1,1-Trifluoro-4-phenylbut-3-en-2-ol (2c)
White solid. Mp 42-43 °C (lit.15 42-43 °C). IR (KBr) 3315, 2924, 1453, 1371 cm-1. 1H NMR (400MHz, CDCl3) δ 4.61-4.68 (1H, m), 6.21 (1H, dd, J = 15.9, 6.5 Hz), 6.86 (1H, d, J = 15.9 Hz), 7.29-7.44 (5H, m). 13C NMR (100MHz, CDCl3) δ 71.6 (q, 2JC-F = 32.4 Hz), 120.5 (q, J = 1.9 Hz), 124.2 (q, J = 281.8 Hz), 126.9 (2C), 128.7 (2C), 128.8, 135.3, 136.4. 19F NMR (373MHz, CDCl3) δ -79.70 (3F, d, J = 7.2 Hz) {lit.15 -79.7 (d, J = 6.4 Hz)}.
4,2,4. 2,2,2-Trifluoro-1-(naphthalen-1-yl)ethanol (2d)
IR (neat) 3399, 2941, 1265, 1168, 1126 cm-1. 1H NMR (400MHz, CDCl3) δ 2.69 (1H, d, J = 4.5 Hz), 5.88-5.94 (1H, m), 7.51-7.60 (3H, m), 7.84 (1H, d, J = 7.3 Hz), 7.90-7.93 (2H, m), 8.08 (1H, d, J = 8.4 Hz). 13C NMR (100MHz, CDCl3) δ 68.8 (q, 2JC-F = 32.2 Hz), 122.7 (q, 4JC-F = 0.9 Hz), 124.6 (q, 1JC-F = 282.5 Hz), 125.1, 125.7 (q, 3JC-F = 1.2 Hz), 125.9, 126.8, 129.0, 129.8 130.1, 131.0, 133.6. 19F NMR (373MHz, CDCl3) δ -77.48 (3F, d, J = 7.2 Hz) {lit.14 -77.25 (d, J = 6.5 Hz)}.
4,2,5. 2,2,2-Trifluoro-1-(furan-2-yl)ethanol (2e)
IR (neat) 3399, 1669, 1504, 1152 cm-1. 1H NMR (400MHz, CDCl3) δ 2.59 (1H, d, J = 7.2 Hz), 5.03-5.10 (1H, m), 6.53-6.44 (1H, m), 6.54 (1H, d, J = 3.2 Hz), 7.47-7.48 (1H, m). 13C NMR (100MHz, CDCl3) δ 67.1 (q, 2JC-F = 34.3 Hz), 110.1 (q, 4JC-F = 0.9 Hz), 110.7, 123.4 (q, 1JC-F = 282.1 Hz), 143.6, 147.1 (q, 3JC-F = 1.6 Hz). 19F NMR (373MHz, CDCl3) δ -78.59 (3F, d, J = 7.2 Hz) {lit.3c -78.42 (d, J = 6.4 Hz)}.
4,2,6. 1-(1-Adamantan-1-yl)-2,2,2-trifluoroethanol (2f)
Yellow solid. Mp 47-49 °C. IR (KBr) 3422, 2907, 2851, 1263, 1167, 1120 cm-1. 1H NMR (400MHz, CDCl3) δ 1.68-1.79 (11H, m), 2.02 (3H, brs), 3.44 (1H, q, J = 8.3 Hz). 13C NMR (100MHz, CDCl3) δ 28.0 (3C), 35.7 (3C), 36.7 (3C), 37.6 (q, 4JC-F = 1.8 Hz), 77.5 (q, 2JC-F = 27.9 Hz), 125.6 (q, 1JC-F = 285.1 Hz). 19F NMR (373MHz, CDCl3) δ -71.55 (3F, d, J = 8.8 Hz). HRMS (EI) calcd for C12H16 F3O (M+) 233.11587, found 233.11668.
4,2,7. 1-Cyclohexyl-2,2,2-trifluoroethanol (2g)
IR (neat) 3399, 3055, 1476, 1162, 1060 cm-1. 1H NMR (400MHz, CDCl3) δ 1.10-1.34 (5H, m), 1.67-2.02 (6H, m), 3.68-3.77 (1H, m). 13C NMR (100MHz, CDCl3) δ 25.7, 25.9, 26.0, 26.7 (q, 4JC-F = 1.0 Hz), 29.2 (q, 3JC-F = 1.2 Hz), 38.1 (q, 4JC-F = 1.0 Hz), 74.3 (q, 2JC-F = 29.1 Hz), 125.3 (q, 1JC-F = 283.3 Hz). 19F NMR (373MHz, CDCl3) δ -76.2 (3F, d, J = 7.1 Hz) {lit.3c -75.98 (d, J = 7.5 Hz)}.
4,2,8. 2,2,2-Trifluoro-1,1-diphenylethanol (2h)
IR (neat) 3456, 3063, 1714, 1155 cm-1. 1H NMR (400MHz, CDCl3) δ 7.34-7.38 (6H, m), 7.48-7.50 (4H, m). 13C NMR (100MHz, CDCl3) δ 79.36 (q, 2JC-F = 28.4 Hz), 125.3 (q, 1JC-F = 286.1 Hz), 127.4 (2C, q, 3JC-F = 1.4 Hz), 128.2 (4C), 128.6 (4C), 139.4 (2C). 19F NMR (373MHz, CDCl3) δ -74.91 (3F, s) (lit.16 -74.21).
4,2,9. 2,2,3,3,3-Pentafluoro-1-(naphthalen-1-yl)propan-1-ol (2i)
The reaction was carried out as in the case of 2a using 1b and 1-naphthaldehyde instead of 1a and benzaldehyde, and 2i was isolated by column chromatography (silica gel, hexane:CH2Cl2=4:1) in 89% yield. White solid. Mp 44-46 °C. IR (KBr) 3465, 3060, 1185, 1135, 1028 cm-1. 1H NMR (400MHz, CDCl3) δ 2.49 (1H, d, J = 4.1 Hz), 6.06 (1H, dt, J = 18.3, 4.5 Hz), 7.52-7.61 (3H, m), 7.84 (1H, d, J = 7.2 Hz), 7.90-7.95 (2H, m), 8.03 (1H, d, J = 8.3 Hz). 13C NMR (100MHz, CDCl3) δ 67.4 (dd, 2JC-F = 26.3 Hz, 2JC-F = 21.9 Hz), 113.3 (ddq, 1JC-F = 262.2 Hz, 1JC-F = 254.8Hz, 2JC-F = 35.7 Hz ), 119.3 (ddq, 2JC-F = 36.7 Hz, 2JC-F = 35.1 Hz, 1JC-F = 287.1 Hz), 122.6 (dd, 3JC-F = 2.4 Hz, 3JC-F = 1.4 Hz), 125.1, 125.9, 126.4, 126.8, 129.0, 130.0, 130.2, 131.2, 133.6. 19F NMR (373MHz, CDCl3) δ -82.19 (3F, s), -120.22 (1F, d, J = 277.6 Hz), -130.51 (1F, dd, J = 276.7, 17.9 Hz){lit.17 -81.54 (m, 3F)}, -118.15 (dd, J = 290.4, 20.7 Hz, 1F), -130.24 (dd, J = 290.4, 20.7 Hz, 1F).
4,2,9. 2,2,3,3,4,4,5,5-Octafluoro-1-(naphthalen-1-yl)pentan-1-ol (2j)
To 1c (626 mg, 2 mmol) were added a 1.0 M THF solution of Et3BHK (2 mL, 2 mmol) and 1-naphthaldehyde (78 mg, 0.5 mmol) successively at room temperature under N2 atmosphere. Then a volatile part was removed under reduced pressure, and the resulting viscous mixture was stirred at 40 °C for 24 h. Then, 30% aqueous H2O2 (2 mL) was added at 0 °C, and after stirring for 1 h, the mixture was extracted with Et2O (30 mL X 3). The combined organic phase was dried over MgSO4 and 2j was isolated by column chromatography (silica gel/CH2Cl2:hexane = 1:4) in 61% yield. White solid. Mp 75-77 °C. IR (KBr) 3398, 1175, 1124, 1041 cm-1. 1H NMR (400MHz, CDCl3) δ 2.57 (1H, s), 6.11 (1H, tt, J =52.1, 5.5 Hz), 7.51-7.60 (3H, m), 7.84 (1H, d, J = 7.3 Hz), 7.90-7.94 (2H, m), 8.00 (1H, d, J = 8.4 Hz). 13C NMR (100MHz, CDCl3) δ 67.3 (dd, 2JC-F = 21.8 Hz, 2JC-F = 30.5 Hz), 104.8-118.3 (4C, m), 122.6, 125.1, 125.9, 126.5, 126.9, 129.0, 130.1, 130.2, 131.3, 133.5. 19F NMR (373MHz, CDCl3) δ -116.37 (1F, d, J = 286.6 Hz), -123.50 to -125.38 (2F, m), -127.40 (1F, d, J = 284.8 Hz), -129.7 to -131.90 (2F, m), -136.94 to -138.82 (2F, m). HRMS (ESI) calcd for C15H9C F8O (M+) 357.05311, found 357.05331.
4,2,10. 2-{(4-Chlorophenyl)sulfanyl}-2,2-difluoro-1-(naphthalen-1-yl)ethanol (5)
The reaction was carried out as in the case of 2i using 4 instead of 1b, and 5 was isolated in 90% yield by column chromatography (silica gel, hexane:CH2Cl2=4:1). Oil. IR (neat) 3434, 2931, 2857, 1276, 1166 cm-1. 1H NMR (400MHz, CDCl3) δ 5.89-5.94 (1H, m), 7.26-7.33 (2H, m), 7.48-7.57 (5H, m), 7.88-7.91 (3H, m), 8.01 (1H, d, J = 8.1 Hz). 13C NMR (100MHz, CDCl3) δ 72.0 (dd, 2JC-F = 27.9 Hz, 2JC-F = 26.2 Hz), 123.1, 124.2, 125.1, 125.7, 126.1, 126.5, 128.9, 129.2 (2C), 129.2 (t, 1JC-F = 286.5 Hz), 129.9 (2C), 131.2, 131.3, 133.6, 136.5, 137.6. 19F NMR (373MHz, CDCl3) δ -79.76 (1F, dd, J = 207.8, 7.2 Hz), -83.60 (1F, dd, J = 207.8, 8.8 Hz). HRMS (ESI) calcd for C18H13Cl2 F2OS (M++Cl) 385.00322, found 385.00203.
4,2,11. 2,2,3,3-Tetrafluoro-1-(4-isobutylphenyl)-3-phenylpropan-1-ol (9)
To a CH2Cl2 solution (1 mL) of 8 (578 mg, 2 mmol) were added a 1.0 M THF solution of Et3BHK (2 mL, 2 mmol) and 4-isobutylbenzaldehyde (81 mg, 0.5 mmol) successively at room temperature under N2 atmosphere. The mixture was stirred at 40 °C for 24 h and then 30% aqueous H2O2 (2 mL) was added at 0 °C. After stirring for 1 h, the mixture was extracted with Et2O (30 mL X 3). The combined organic phase was dried over MgSO4 and 9 was isolated by column chromatography (silica gel/AcOEt:hexane = 1:10) in 60% yield. White solid. Mp 54-55 °C. IR (KBr) 3466, 2960, 1069 cm-1. 1H NMR (400MHz, CDCl3) δ 0.89 (6H, d, J = 6.7 Hz), 1.80-1.91 (1H, m), 2.39 (1H, d, J = 4.7 Hz), 2.47 (1H, d, J = 7.2 Hz), 5.14 (1H, dt, J = 17.3, 5.1 Hz), 7.15 (2H, d, J = 8.1 Hz), 7.34 (2H, d, J = 8.0 Hz), 7.43-7.52 (3H, m), 7.58 (2H, d, J = 7.4 Hz). 13C NMR (100MHz, CDCl3) δ 22.3 (2C), 30.1, 45.1, 72.0 (dd, 2JC-F = 28.8 Hz, 2JC-F = 22.4 Hz), 115.4 (tt, 1JC-F = 260.8 Hz, 2JC-F = 35.3 Hz), 117.2 (tt, 1JC-F = 253.0 Hz, 2JC-F = 34.1 Hz), 126.7 (t, 3JC-F = 6.7 Hz), 127.8 (2C), 128.2 (2C), 129.1 (2C), 130.9 (2C, t, 2JC-F = 24.3 Hz), 131.0 (t, 4JC-F = 1.4 Hz), 132.5, 142.8. 19F NMR (373MHz, CDCl3) δ -109.50 to -110.99 (2F, m), -108.29 (1F, dd, J = 275.5, 6.2 Hz), -108.29 (1F, dd, J = 275.5, 17.6 Hz). HRMS (EI) calcd for C19H19 F4O (M+) 339.13775, found 339.13808.

ACKNOWLEDGEMENTS
We are grateful to Asahi Glass Co., Ltd., and Daikin Industries, Ltd., for their donation of IF5 and 2,2,3,3,4,4,5,5-octafluoropentanol, respectively.

References

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