European Journal of Organic Chemistry
10.1002/ejoc.201600770
FULL PAPER
3H); 19F NMR (471 MHz, CDCl3) δ ppm -96.24; 13C NMR (126 MHz,
CDCl3) δ ppm 164.8 (t, J = 33.3), 163.4, 160.2 (t, J = 2.6), 113.4 (t, J =
247.6), 102.6 (t, J=24.0), 91.4, 62.4, 56.1, 55.3, 14.0; IR (KBr, cm-1): max
= 2987, 2928, 1772, 1593, 1466, 1233, 1159, 1091, 986, 837, 759.
128.50 (t, J = 23.2), 127.39, 126.36, 124.94 (t, J = 9.4), 124.60, 124.23 (t,
J = 3.1), 114.50 (t, 253.2), 63.30, 13.78; IR (KBr, cm-1): max = 3057, 2986,
1765, 1285, 1127, 1089, 1019, 804, 779.
Ethyl 2-(anthracen-9-yl)-2,2-difluoroacetate (3o)
Ethyl 2,2-difluoro-2-(5-iodo-2-methoxyphenyl)acetate (3i)
Colorless liquid (130.5 mg, 87%). 1H NMR (500 MHz, CDCl3) δ ppm 8.65
(d, J = 9.1, 2H), 8.57 (s, 1H), 8.01 (d, J = 7.8, 2H), 7.58 (t, J = 6.5, 2H),
7.49 (t, J = 7.1, 2H), 4.34 (q, J = 7.1, 2H), 1.26 (t, J = 7.2, 3H); 19F NMR
(471 MHz, CDCl3) δ ppm major: -89.26; minor: -97.95; minor: -100.49;
13C NMR (126 MHz, CDCl3) δ ppm 164.78 (t, J = 34.8), 132.66, 131.47,
130.24, 129.25, 127.34, 125.42 (t, J = 8.9), 125.17, 123.56 (t, J = 23.6),
117.10 (t, J = 254.1), 63.57, 14.00. HRMS m/z(ESI) calcd. for C13H15F2O5
(M + H) 289.0882, found 289.0886.
Colorless liquid (158.5 mg, 89%). 1H NMR (500 MHz, CDCl3) δ ppm 7.88
(s, 1H), 7.72 (d, J = 8.2, 1H), 6.71 (d, J = 8.6, 1H), 4.31 (q, J = 7.1, 2H),
3.77 (s, 3H), 1.28 (t, J = 7.1, 3H); 19F NMR (471 MHz, CDCl3) δ ppm -
103.08; 13C NMR (126 MHz, CDCl3) δ ppm 163.5 (t, J = 33.6), 156.6 (t, J
= 4.9), 141.1, 135.1 (t, J = 7.9), 124.1 (t, J = 24.2), 113.7, 111.3 (t, J =
249.5), 82.3, 62.9, 55.9, 14.0; IR (KBr, cm-1): max = 2981, 2945, 1775,
1596, 1488, 1303, 1260, 1093, 1023, 813, 679. HRMS m/z(ESI) calcd.
for C11H12F2IO3 (M+H) 356.9794, found 356.9791.
Ethyl 2,2-difluoro-2-(thiophen-2-yl)acetate (3p)
Ethyl 2-(5-bromo-2-methoxyphenyl)-2,2-difluoroacetate (3j)
1
Colorless liquid (85.6 mg, 83%). H NMR (500 MHz, CDCl3) δ ppm 7.48
Colorless liquid (143.7 mg, 93%). 1H NMR (500 MHz, CDCl3) δ ppm 7.73
(d, J = 2.5, 1H), 7.54 (dd, J = 8.8, 2.2, 1H), 6.82 (d, J = 8.9, 1H), 4.31 (q,
J = 7.1, 2H), 3.78 (s, 3H), 1.28 (t, J = 7.1, 3H); 19F NMR (471 MHz,
CDCl3) δ ppm -103.11; 13C NMR (126 MHz, CDCl3) δ ppm 163.5(t,
J=33.6), 155.9 (t, J = 4.8), 135.1, 129.4 (t, J = 7.9), 123.8 (t, J = 24.5),
(d, J = 4.9, 1H), 7.39 (d, J = 3.6, 1H), 7.06 (t, J = 3.8, 1H), 4.36 (q, J = 7.1,
2H), 1.34 (t, J = 7.1, 3H); 19F NMR (471 MHz, CDCl3) δ-92.78; 13C NMR
(126 MHz, CDCl3) δ ppm 163.40 (t, J = 35.1), 134.11 (t, J = 30.2),
129.12, 128.58 (t, J = 5.5), 127.24, 111.85 (t, J = 250.3), 63.55, 13.93; IR
(KBr, cm-1): max = 3096, 2963, 1729, 1655, 1406, 1239, 1057, 738, 672.
113.2, 112.9, 111.5 (t, J = 249.5), 62.9, 56.1, 14.0; IR (KBr, cm-1): max
=
2-(2,5-dimethylphenyl)-2,2-difluoro-1-morpholinoethanone (3q)
2981, 2949, 1773, 1491, 1265, 1104, 1022, 812. HRMS m/z(ESI) calcd.
for C11H12BrF2O3 (M + H) 308.9932, found 308.9935.
Colorless liquid (70.0 mg, 52%). 1H NMR (500 MHz, CDCl3) δ ppm 7.27
(s, 1H), 7.18 - 7.10 (m, 2H), 3.71 (s, 4H), 3.50 (s, 4H), 2.34 (s, 3H), 2.32
(s, 3H), 19F NMR (470 MHz, CDCl3) δ ppm -94.04, 13C NMR (126 MHz,
CDCl3) δ ppm 162.2 (t, J = 30.7 Hz), 135.4, 133.5 (t, J = 2.9 Hz), 132.1,
131.6 (t, J = 22.8 Hz), 131.4, 126.1 (t, J = 8.1 Hz), 116.5 (t, J = 251.2 Hz),
66.7, 66.4, 46.7 (t, J = 4.1 Hz), 43.5, 20.9, 19.4 (t, J = 2.2 Hz); IR (KBr,
cm-1): max = 2967, 2924, 2858, 1676, 1444, 1257, 1112, 1073, 820, 757.
HRMS m/z(ESI) calcd. for C14H18F2NO2 (M + H) 270.1300, found
270.1304.
Ethyl 2-(5-chloro-2-methoxyphenyl)-2,2-difluoroacetate (3k)
1
Colorless liquid (78.1 mg, 59%). H NMR (500 MHz, CDCl3) δ ppm 7.58
(d, J = 2.7, 1H), 7.38 (dd, J = 8.8, 2.5, 1H), 6.86 (d, J = 8.8, 1H), 4.30 (q,
J=7.1, 2H), 3.77 (s, 3H), 1.27 (t, J = 7.1, 3H); 19F NMR (471 MHz, CDCl3)
δ ppm -103.10; 13C NMR (126 MHz, CDCl3) δ ppm 163.5 (t, J = 33.6),
155.4 (t, J = 4.9), 132.1 (t, J = 1.7), 126.5 (t, J = 7.9), 125.8, 123.4 (t, J =
24.4), 112.8, 111.5 (t, J = 247.8), 62.9, 56.1, 13.9; IR (KBr, cm-1): max
=
2983, 2945, 1773, 1495, 1270, 1110, 1021, 816, 684. HRMS m/z(ESI)
calcd. for C11H12ClF2O3 (M + H) 265.0438, found 265.0443.
Diethyl ((2,5-dimethylphenyl)difluoromethyl)phosphonate (3r)
Colorless liquid (58.5 mg, 40%). 1H NMR (500 MHz, CDCl3) δ ppm 7.24
(s, 1H), 7.07-7.01 (m, 2H), 4.10 (m, 2H), 4.02 (m, 2H), 2.42 (s, 3H), 2.26
(s, 3H), 1.26 (t, J = 7.1 Hz, 6H), 19F NMR (470 MHz, CDCl3) δ ppm -
104.21 (dd, J = 117.3, 3.5 Hz), 13C NMR (125 MHz, CDCl3) δ ppm 135.2,
134.4 (q, J = 2.8 Hz), 132.2 (d, J = 1.4 Hz), 131.4 (q, J = 1.8 Hz), 130.3
(td, J = 20.2, 13.5 Hz), 128.1 (td, J = 9.1, 2.3 Hz), 119.8 (td, J = 264.4,
217.7 Hz), 64.7, 64.6, 20.9, 20.2 (t, J = 4.2 Hz), 16.4,16.3. HRMS
m/z(ESI) calcd. for C13H20F2O3P (M + H) 293.1113, found 293.1115.
Ethyl 2,2-difluoro-2-(5-fluoro-2-methoxyphenyl)acetate (3l)
Colorless liquid (59.6 mg, 48%).1H NMR (500 MHz, CDCl3) δ ppm 7.34
(dd, J = 8.5, 3.1, 1H), 7.13 (td, J = 8.8, 3.0, 1H), 6.88 (dd, J = 8.0, 4.0,
1H), 4.31 (q, J = 7.1, 2H), 3.77 (s, 3H), 1.28 (t, J = 7.1, 3H), 19F NMR
(471 MHz, CDCl3) δ ppm -102.91(s), -122.39 (m); -102.10(d, J = 7.8); 13
C
NMR (126 MHz, CDCl3) δ ppm 163.6(t, J = 33.7), 156.7 (d, J = 240.2),
152.3 - 152.9(m), 123.3 (td, J = 24.6, 7.6), 118.6(d, J = 22.9), 113.8 (dt, J
= 26.0, 7.8), 112.8 (d, J = 7.9), 111.5 (t, J = 249.1), 62.9, 56.3, 13.9; IR
(KBr, cm-1): max = 2982, 1772, 1502, 1273, 1088, 1027, 887, 720.
Methyl 3-(2-ethoxy-1,1-difluoro-2-oxoethyl)-4-methoxybenzoate (3m)
Acknowledgements
Colorless liquid (77.8 mg, 54%). 1H NMR (500 MHz, Chloroform-d) δ ppm
8.30 (d, J = 2.2 Hz, 1H), 8.14 (dd, J = 8.7, 2.1 Hz, 1H), 6.96 (d, J = 8.7
Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 3.88 (s, 3H), 3.85 (s, 3H), 1.26 (t, J =
7.1 Hz, 3H).19F NMR (471 MHz, Chloroform-d) δ ppm -103.30 .13C NMR
(126 MHz, Chloroform-d) δ ppm 166.0, 163.6 (t, J = 33.8 Hz), 160.2 (t, J
= 4.6 Hz), 134.4 (t, J = 1.4 Hz), 128.3 (t, J = 7.6 Hz), 122.8, 122.0 (t, J =
24.5 Hz), 111.8 (t, J = 249.1 Hz), 111.0, 62.8, 56.1, 52.2, 13.9; IR (KBr,
cm-1): max = 2986, 2954, 1776, 1722, 1616, 1309, 1275, 1112, 1030,
771, 682. HRMS m/z(ESI) calcd. for C13H15F2O5 (M + H) 289.0882, found
289.0886.
This work was financially supported by the National Natural
Science Foundation of China (21172141, 21302121, 21572128)
and the Science Foundation of Shanghai Municipal Commission
of Sciences and Technology (15230724800). We thank the
Laboratory of Micro-structures of Shanghai University for
structural analysis.
Keywords: Difluoromethylation • Radical • Silver-mediated •
Regioselectivity • Arenes
Ethyl 2,2-difluoro-2-(naphthalen-1-yl)acetate(3n)
Colorless liquid (111.3 mg, 89%). 1H NMR (500 MHz, CDCl3) δ ppm 8.32
(d, J = 8.7, 1H), 7.97 (d, J = 8.3, 1H), 7.94 (d, J = 7.2, 1H), 7.91 (d, J =
8.2, 1H), 7.64-7.58 (m, 1H), 7.58-7.51 (m, 2H), 4.31 (q, J = 7.2, 2H), 1.24
(t, J = 7.2, 3H); 19F NMR (471 MHz, CDCl3) δ ppm -99.85; 13C NMR (126
MHz, CDCl3) δ ppm 164.46 (t, J = 34.8), 133.93, 132.02, 129.40, 128.94,
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Begue, D. Bonnet-Delpon, Bioorganic and Medicinal Chemistry of