Full Paper
GC–MS analysis of the crude product indicated a major (represents
product 2d) and a minor isomer with the relative ratio 10:1. Yield:
low intensity. 19F NMR (282 MHz, [D ]MeOD): δ = –63.89 (minor),
–64.82 ppm (major). MS (70 eV): m/z (%) = 187 [M ] (54), 168 (19),
4
+
1
3.9 mg (52.6 μmol, 26 %) light yellow, viscous oil; R = 0.60 (cyclo-
167 (83), 140 (8), 139 (100), 113 (5), 112 (9), 88 (17), 75 (14), 69 (7),
64 (8), 63 (12), 62 (8), 44 (5). The spectra are in accordance with
f
1
hexane/EtOAc, 1:1); H NMR (300.13 MHz, CDCl ): δ = 7.34 (s, 1 H,
CHarom), 7.18 (s, 1 H, CHarom), 3.962 (s, 3 H, OCH ), 3.957 (s, 3 H, previously reported data.
OCH ), 3.92 ppm (s, 3 H, OCH ); C NMR (125.69 MHz, CDCl ): δ =
1
3
[
29]
3
1
3
3
3
3
3
66.9 (C ), 150.9 (C ), 150.8 (C ), 123.8 [C , q, J(C,F) = 2.0 Hz], 123.6
q q q q
1
2
Acknowledgments
[q, J(C,F) = 272.7 Hz, C , CF ], 122.6 [C , q, J(C,F) = 33.3 Hz], 113.5
q
3
q
3
(
(
CHarom), 109.7 [q, J(C,F) = 5.8 Hz, CH
], 56.4 (2 × CH ), 52.8 ppm
arom 3
We thank Prof. Dr. Klaus Zangger and Bernd Werner for NMR
measurements. Open access funding provided by University of
Graz. MF acknowledges the Austrian Science Fund FWF (Project
P 31276).
CH ); 19F NMR (282 MHz, CDCl ): δ = –58.47 ppm. IR (ATR): ν˜ =
3
3
2
1
6
2
1
953, 2855, 1734, 1605, 1528, 1463, 1436, 1399, 1356, 1292, 1270,
211, 1173, 1115, 1027, 987, 929, 876, 830, 791, 772, 744, 730, 694,
–1
+
52, 567, 542 cm . MS (70 eV): m/z (%) = 264 [M ] (59), 234 (12),
33 (100), 205 (19), 193 (5), 190 (5), 189 (5), 187 (6), 161 (9), 147 (9),
+
19 (5), 69 (5). HR-MS (HPLC-TOF-MS): m/z [M + NH ] calcd. for Keywords: Trifluoromethylation · Phenol · Hydroquinone ·
4
+
C H F NO : 282.094769, found 282.094955.
Catalysis · Copper
11
15
3
4
1
-[4-Hydroxy-3-(trifluoromethyl)phenyl]ethan-1-one (2e):
2
4
7.2 mg (200 μmol, 1 equiv.) 1-(4-hydroxyphenyl)ethan-1-one (1e),
8 h reaction time, purification via preparative reversed-phase
[
1] S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008,
7, 320–330.
3
chromatography. Method: column oven 30 °C, flow rate 14 mL/min;
.0–5.0 min MeCN/H O = 3:97 (v/v), 5.0–30.0 min linear increase to
[2] T. Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2013, 52, 8214–
8264; Angew. Chem. 2013, 125, 8372.
[3] W. Zhu, J. Wang, S. Wang, Z. Gu, J. L. Aceña, K. Izawa, H. Liu, V. A. Solosho-
nok, J. Fluorine Chem. 2014, 167, 37–54.
0
2
MeCN/H O = 55:45 (v/v), 30.0–31.0 min linear increase to MeCN/
2
H O = 100:0 (v/v), 31.0 min–36.0 min hold MeCN/H O = 100:0
2
2
[
[
[
4] H.-J. Böhm, D. Banner, S. Bendels, M. Kansy, B. Kuhn, K. Müller, U. Obst-
Sander, M. Stahl, ChemBioChem 2004, 5, 637–643.
5] A. Studer, Angew. Chem. Int. Ed. 2012, 51, 8950–8958; Angew. Chem.
(
(
[
v/v). Yield: 7.6 mg (37.2 μmol, 19 %) pale yellow solid; R = 0.40
cyclohexane/EtOAc, 1:1); m.p. 171–172 °C; H NMR (300.13 MHz,
f
1
4
D ]MeOD): δ = 8.14 [d, J(H,H) = 2.0 Hz, 1 H, CHarom], 8.06 [dd,
4
2012, 124, 9082.
3
4
3
J(H,H) = 8.6, J(H,H) = 2.1 Hz, 1 H, CH
arom
H, CHarom], 5.48 (br. s, 1 H, OH), 2.56 ppm (s, 3 H, CH3); C NMR
], 7.01 [d, J(H,H) = 8.6 Hz,
6] X.-F. Wu, H. Neumann, M. Beller, Chem. Asian J. 2012, 7, 1744–1754.
13
1
[7] C. Le, T. Q. Chen, T. Liang, P. Zhang, D. W. C. MacMillan, Science 2018,
360, 1010–1014.
[8] H. Guyon, H. Chachignon, D. Cahard, Beilstein J. Org. Chem. 2017, 13,
2764–2799.
[9] C. Alonso, E. Martínez de Marigorta, G. Rubiales, F. Palacios, Chem. Rev.
2015, 115, 1847–1935.
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Soc., Perkin Trans. 1 1990, 39, 2293–2299.
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202.
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14] T. Kino, Y. Nagase, Y. Ohtsuka, K. Yamamoto, D. Uraguchi, K. Tokuhisa, T.
Yamakawa, J. Fluorine Chem. 2010, 131, 98–105.
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Kurjan, B. Gutmann, C. O. Kappe, Chem. Eur. J. 2017, 23, 176–186.
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[19] K. Stanek, R. Koller, A. Togni, J. Org. Chem. 2008, 73, 7678–7685.
[20] M. S. Wiehn, E. V. Vinogradova, A. Togni, J. Fluorine Chem. 2010, 131,
3
(75.47 MHz, [D ]MeOD): δ = 198.2 (C , C=O), 161.7 [C , q, J(C,F) =
4
q
q
3
1
1
1
–
.6 Hz], 135.2 (CH
), 129.6 (C ), 128.9 [q, J(C,F) = 5.2 Hz, CHarom],
25.0 [C , q, J(C,F) = 271.5 Hz], 118.1 [C , q, J(C,F) = 31.2 Hz],
17.7 (CHarom), 26.3 ppm (CH3); F NMR (282 MHz, [D ]MeOD): δ =
64.46 ppm. MS (70 eV): m/z (%) = 204 [M ] (33), 190 (6), 189 (71),
arom
q
1
2
q
q
1
9
4
+
[
[
1
85 (9), 170 (8), 169 (100), 141 (12), 127 (5), 113 (25), 79 (5), 63 (18),
4
3 (17). The succession of signals in the NMR spectra in [D ]MeOD
4
29]
[
are in accordance with previously reported data in CDCl3.
[
4
-Hydroxy-3-(trifluoromethyl)benzonitrile (major-2f )/4-
Hydroxy-2-(trifluoromethyl)benzonitrile (minor-2f): 23.8 mg
200 μmol, 1 equiv.) 4-hydroxybenzonitrile (1f), 48 h reaction time,
[
[
(
purification via preparative reversed-phase chromatography.
Method: column oven 30 °C, flow rate 14 mL/min; 0.0–5.0 min
MeCN/H O = 3:97 (v/v), 5.0–30.0 min linear increase to MeCN/H O =
[
2
2
[
5
5:45 (v/v), 30.0–31.0 min linear increase to MeCN/H O = 100:0
2
(
v/v), 31.0 min–36.0 min hold MeCN/H O = 100:0 (v/v). The product
2
was obtained as an inseparable mixture of the major and minor
1
regioisomer (ratio = 79:21, determined via H-NMR integrals, 20 s
9
51–957.
delay). Yield: 10.8 mg (57.6 μmol, 29 %) pale yellow solid; R = 0.41
f
1
[21] H. Egami, T. Ide, Y. Kawato, Y. Hamashima, Chem. Commun. 2015, 51,
(
[
(
cyclohexane/EtOAc, 1:1); m.p. 154–158 °C; H NMR (300.13 MHz,
D ]MeOD): δ = 7.89 [d, J(H,H) = 2.0 Hz, 1 H, C-2major], 7.81–7.73
4
16675–16678.
4
[
22] J.-J. Yang, R. L. Kirchmeier, J. M. Shreeve, J. Org. Chem. 1998, 63, 2656–
660.
4
m, 1.28 H, C-6major, C-6minor), 7.22 [d, J(H,H) = 2.4 Hz, 0.27 H, C-
2
1
3
3minor], 7.14–7.05 ppm (m, 1.28 H, C-5major, C-5
); C NMR
minor
3
[
23] L. Li, X. Mu, W. Liu, Y. Wang, Z. Mi, C.-J. J. Li, J. Am. Chem. Soc. 2016, 138,
(
75.47 MHz, CDCl ): δ = 159.8 (C-4
), 157.7 [q, J(C,F) = 1.7 Hz,
], 137.0 (C-6minor), 131.9
], 122.9 [q, J(C,F) = 273.0 Hz, CF3,major],
3
minor
5809–5812.
4
C-4
[
1
1
1
], 137.4 [q, J(C,F) = 0.6 Hz,C-6
[24] B. Chang, H. Shao, P. Yan, W. Qiu, Z. Weng, R. Yuan, ACS Sustainable Chem.
Eng. 2017, 5, 334–341.
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mond, Angew. Chem. Int. Ed. 2014, 53, 11868–11871; Angew. Chem. 2014,
126, 12062.
major
3
major
1
q, J(C,F) = 5.0 Hz, C-2
major
2
19.0 (C-5minor), 118.9 (C-5major), 118.1 [q, J(C,F) = 32.0 Hz, C-3major],
17.8 (CNmajor), 115.9 (CNminor), 114.8 [q, J(C,F) = 4.7 Hz, C-3minor],
04.3 (C-1major), 101.2 ppm (C-1minor); C NMR (75.47 MHz, [D6]-
acetone): δ = 161.7 (C-4minor), 159.6 [q, J(C,F) = 1.7 Hz, C-4major],
3
1
3
3
[26] B. R. Langlois, E. Laurent, N. Roidot, Tetrahedron Lett. 1991, 32, 7525–
7
528.
3
1
1
37.6 (C-6major), 137.2 (C-6minor), 131.6 [q, J(C,F) = 5.4 Hz, C-2major],
[
27] J.-B. Liu, C. Chen, L. Chu, Z.-H. Chen, X.-H. Xu, F.-L. Qing, Angew. Chem.
Int. Ed. 2015, 54, 11839–11842; Angew. Chem. 2015, 127, 12005.
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[29] R. C. Simon, E. Busto, N. Richter, V. Resch, K. N. Houk, W. Kroutil, Nat.
Commun. 2016, 7, 13323.
23.1 [q, 1J(C,F) = 271.8 Hz, CF3,major], 119.4 (C-5minor), 118.2
2
(C-5major), 117.8 (CN
), 177.7 [q, J(C,F) = 31.6 Hz, C-3major], 114.3
q, J(C,F) = 5.1 Hz, C-3minor], 102.7 ppm (C-1major). The remaining
major
3
[
quaternary C-atoms of the minor-isomer were not detected due to
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
8
© 0000 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim