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Synlett 2003(4): 0527-0531
DOI: 10.1055/s-2003-37517
LETTER
© Georg Thieme Verlag Stuttgart · New York

Superacid Catalyzed Hydroxyalkylation of Aromatics with Ethyl Trifluoro­pyruvate: A New Synthetic Route to Mosher’s Acid Analogs

G. K. Surya Prakash*, Ping Yan, Béla Török, George A. Olah*
Loker Hydrocarbon Research Institute, Department of Chemistry, University of Southern California, University Park, Los Angeles, CA 90089-1661, USA.
Fax: +1(213)7406270; e-Mail: gprakash@usc.edu;
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Publication History

Received 20 January 2003
Publication Date:
26 February 2003 (online)

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Abstract

A new superacid catalyzed Friedel-Crafts hydroxy­alkylation of aromatics with ethyl trifluoropyruvate is described. The trifluoromethanesulfonic acid or gallium(III) trifluoromethanesulfonate catalyzed reactions give α-hydroxy α-trifluoromethyl phenyl acetic acid ethyl ester and its derivatives (analogs of Mosher’s acid) in good yields for both highly activated hetero­aromatics and substituted benzenes.

Key words

Friedel-Crafts hydroxyalkylation - α-trifluoromethyl alcohol - gallium triflate - trifluoromethanesulfonic acid - Mosher’s acid

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14

New compounds were characterized by NMR (1H, 19F, 13C) spectroscopy using Bruker AM-360 spectrometer. The spectra were recorded in CDCl3 using TMS and CCl3F as internal standards.
2,5-Di(α-carboethoxy-α-hydroxytrifluoroethyl)-pyrrole: 1H NMR (360 MHz, CDCl3): δ 1.39 (t, J = 7.3 Hz, 6 H), 4.34-4.53 (m, 6 H), 6.44 (s, 1 H), 6.45 (s, 1 H), 9.18 (br s). 19F NMR (338 MHz, CDCl3): δ -78.92 (s). 13C NMR (90 MHz, CDCl3): δ 167.7, 122.4 (q, J = 285.5 Hz), 123.0, 122.9, 75.0 (q, J = 32.3 Hz), 64.8, 13.8.
3,3,3-Trifluoro-2-hydroxy-2-(4-methylphenyl)-propion-ic acid ethyl ester: 1H NMR (250 MHz, CDCl3): δ 1.37 (t, J = 7.2 Hz, 3 H), 2.36 (s, 3 H), 4.30 (s, -OH), 4.31-4.52 (m, 2 H), 7.21 (d, J = 8.5 Hz, 2 H), 7.67 (d, 2 H). 19F NMR (470 MHz, CDCl3): δ -76.98. 13C NMR (125 MHz, CDCl3): δ 169.1, 139.6, 130.0, 129.1, 126.7, 123.1 (q, J = 285.5 Hz), 77.7 (q, J = 30.2 Hz), 64.3, 21.1, 13.9.
3,3,3-Trifluoro-2-hydroxy-2-(4-methoxyphenyl)-prop-ionic acid ethyl ester: 1H NMR (360 MHz, CDCl3): δ 1.38 (t, 3 H, J = 7.3 Hz), 3.82 (s, 3 H), 4.29 (s, -OH), 4.33-4.52 (m, 2 H), 6.93 (d, 1 H, J = 9.0 Hz), 7.71 (d, 1 H). 19F NMR (338 MHz, CDCl3): δ -77.22 (s). 13C NMR (90 MHz CDCl3): δ 169.1, 160.5, 128.2, 124.8, 122.4 (q, J = 285.8 Hz), 113.8, 77.5 (q, J = 30.5 Hz), 64.3, 55.3, 13.9.
3,3,3-Trifluoro-2-hydroxy-2-(4- t -butylphenyl)-propionic acid ethyl ester:
1H NMR (360 MHz, CDCl3): δ 1.32 (s, 9 H), 1.38 (t, J = 7.0 Hz, 3 H), 4.30 (s, 1 H), 4.31-4.51 (m, 2 H), 7.42 (m, 2 H), 7.70 (d, 2 H, J = 8.3 Hz). 19F NMR (338 MHz, CDCl3): δ -76.93 (s). 13C NMR (90 MHz, CDCl3): δ 169.2, 152.7, 130.0, 126.6, 125.5, 123.2 (q, J = 285.6 Hz), 77.8 (q, J = 30.9 Hz), 64.4, 34.7, 31.3, 14.0.
3,3,3-Trifluoro-2-hydroxy-2-(4-fluorophenyl)-propionic acid ethyl ester:
1H NMR (360 MHz, CDCl3): δ 1.38 (t, J = 7.5 Hz, 3 H), 4.39 (s, 1 H), 4.34-4.53 (m, 2 H), 7.09 (m, 2 H), 7.80 (m, 2 H). 19F NMR (338 MHz, CDCl3): δ -77.20 (s), -112.66 (q, J = 9.1 Hz). 13C NMR (90 MHz, CDCl3): δ 168.75, 163.5 (d, J = 248.8 Hz), 128.9 (dd, J = 8.6 Hz, 2.7 Hz), 128.6 (d, J = 3.3 Hz), 122.9 (q, J = 285.7 Hz), 115.4 (d, J = 22.8 Hz), 77.4 (q, J = 30.5 Hz), 64.6, 13.8.
3,3,3-Trifluoro-2-hydroxy-2-(4-chlorophenyl)-propionic acid ethyl ester:
1H NMR (360 MHz, CDCl3): δ 1.38 (t, 3 H, J = 7.5 Hz), 4.38 (s, 1 H), 4.30-4.52 (m, 2 H), 7.39 (d, 2 H, J = 8.6 Hz), 7.75 (d, 2 H). 19F NMR (338 MHz, CDCl3): δ -77.09 (s). 13C NMR (90 MHz, CDCl3): δ 168.7, 136.0, 131.4, 128.7, 128.5, 122.9 (q, J = 285.9 Hz), 77.5 (q, J = 30.6 Hz), 64.8, 13.9.
3,3,3-Trifluoro-2-hydroxy-2-(2,5-dimethylphenyl)-pro-pionic acid ethyl ester: 1H NMR (360 MHz, CDCl3): δ 1.38 (t, 3 H, J = 7.3 Hz), 3.82 (s, 3 H), 4.29 (s, 1 H), 4.33-4.52 (m, 2 H), 6.93 (d, 1 H, J = 9.0 Hz), 7.71 (d, 1 H). 19F NMR (338 MHz, CDCl3): δ
-73.65 (s). 13C NMR (90 MHz, CDCl3): δ 169.9, 135.2, 134.5, 132.5, 131.3, 129.9, 128.0 (q, J = 3.8 Hz), 123.5 (q, J = 288.1 Hz), 79.6 (q, J = 28.8 Hz), 64.1, 21.2, 20.0, 13.8.
3,3,3-Trifluoro-2-hydroxy-2-(2,4,6-trimethylphenyl)-propionic acid ethyl ester:
1H NMR (360 MHz, CDCl3): δ 1.26 (t, J = 7.0 Hz, 3 H), 2.18 (s, 3 H), 2.35(s, 6 H), 3.23 (s, -OH), 4.17-4.33 (m, 2 H), 6.80 (s, 2 H). 19F NMR (338 MHz, CDCl3): δ -76.17 (s). 13C NMR (90 MHz, CDCl3): δ 168.5, 137.6, 137.5, 131.2, 126.8, 123.0 (q, J = 284.8 Hz), 80.3 (q, J = 30.2 Hz), 61.7, 21.6, 21.5, 19.4, 12.6.