The Journal of Organic Chemistry
Article
CDCl3) δ −62.06, −62.60; HRMS (Q-TOF, ESI) calcd for
C21H15F6O3 [M + H]+ 429.0920, found 429.0928.
119.9 (q, J = 276.3 Hz), 52.2, 32.4, 20.0; 19F NMR (377 MHz, CDCl3)
δ −61.75; HRMS (Q-TOF, ESI) calcd for C21H18F3O3 [M + H]+
375.1203, found 375.1212.
Methyl 5-(4-Cyanobenzyl)-4-phenyl-2-(trifluoromethyl)furan-3-
carboxylate (3j). Oil (63 mg, 82% yield); 1H NMR (400 MHz,
CDCl3) δ 7.56 (d, J = 8.3 Hz, 2H), 7.38 (dd, J = 5.3, 1.7 Hz, 3H), 7.20
(t, J = 7.6 Hz, 4H), 4.01 (s, 2H), 3.71 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 161.6, 151.1, 142.0 (q, J = 52.5 Hz), 132.7, 130.0, 129.6,
129.3, 129.0, 128.7, 128.6, 128.5, 127.5, 125.6, 124.7, 121.3 (q, J =
267.4 Hz), 52.4, 32.4; 19F NMR (377 MHz, CDCl3) δ −62.05; HRMS
(Q-TOF, ESI) calcd for C21H15F3NO3 [M + H]+ 386.0999, found
386.1007.
Methyl 5-Benzyl-4-(p-tolyl)-2-(trifluoromethyl)furan-3-carboxy-
1
late (3r). Oil (73 mg, 98% yield); H NMR (400 MHz, CDCl3) δ
7.20 (t, J = 7.2 Hz, 2H), 7.16−7.10 (m, 3H), 7.06 (dd, J = 11.7, 7.6 Hz,
4H), 3.87 (s, 2H), 3.65 (s, 3H), 2.30 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 162.2, 152.8, 141.8 (q, J = 49.0 Hz), 138.0, 136.9, 129.6,
128.8, 128.5, 127.8, 127.4, 126.9, 123.8, 120.2 (q, J = 276.5 Hz), 117.5,
52.3, 32.3, 21.39; 19F NMR (377 MHz, CDCl3) δ −62.10; HRMS (Q-
TOF, ESI) calcd for C21H18F3O3 [M + H]+ 375.1203, found 375.1209.
Methyl 5-Benzyl-4-(4-chlorophenyl)-2-(trifluoromethyl)furan-3-
carboxylate (3s). Oil (70 mg, 89% yield); 1H NMR (400 MHz,
CDCl3) δ 7.28 (d, J = 8.3 Hz, 2H), 7.23−7.13 (m, 3H), 7.11 (d, J = 8.1
Hz, 2H), 7.02 (d, J = 7.5 Hz, 2H), 3.85 (s, 2H), 3.65 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 161.8, 153.1, 141.8 (q, J = 39.0 Hz),
136.5, 134.4, 131.2, 130.7, 129.2, 129.1, 128.5, 128.4, 127.1, 122.0,
120.8 (q, J = 268.5 Hz), 52.4, 32.3; 19F NMR (377 MHz, CDCl3) δ
−62.10; HRMS (Q-TOF, ESI) calcd for C20H15ClF3O3 [M + H]+
395.0656, found 395.0662.
Methyl 5-(4-Chlorobenzyl)-4-phenyl-2-(trifluoromethyl)furan-3-
carboxylate (3k). Oil (76 mg, 97% yield); 1H NMR (400 MHz,
CDCl3) δ 7.29 (d, J = 7.2 Hz, 3H), 7.20−7.11 (m, 4H), 6.94 (d, J = 8.5
Hz, 2H), 3.82 (s, 2H), 3.62 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
161.9, 152.3, 141.2 (q, J = 42.2 Hz), 135.1, 133.2, 132.9, 130.9, 130.3,
129.8, 129.1, 128.8, 128.3, 124.1 (q, J = 264.6 Hz), 117.4, 52.3, 32.0;
19F NMR (377 MHz, CDCl3) δ −62.03; HRMS (Q-TOF, ESI) calcd
for C20H15ClF3O3 [M + H]+ 395.0656, found 395.0658.
Methyl 5-(2,3-Dichlorobenzyl)-4-phenyl-2-(trifluoromethyl)furan-
1
Methyl 5-Benzyl-2-(trifluoromethyl)-4-(4-(trifluoromethyl)-
3-carboxylate (3l). Oil (81.5 mg, 95% yield); H NMR (400 MHz,
1
phenyl)furan-3-carboxylate (3t). Oil (77 mg, 90% yield); H NMR
CDCl3) δ 7.31−7.24 (m, 4H), 7.17−7.13 (m, 2H), 7.02 (t, J = 7.9 Hz,
1H), 6.86 (dd, J = 7.7, 1.4 Hz, 1H), 4.06 (s, 2H), 3.66 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 161.9, 150.8, 141.3 (q, J = 42.0 Hz),
136.7, 133.5, 132.2, 130.1, 129.5, 129.3, 128.5, 128.4, 128.2, 127.8,
127.4, 125.0 (q, J = 269.2 Hz), 119.8, 52.4, 31.0. 19F NMR (377 MHz,
CDCl3) δ −62.10; HRMS (Q-TOF, ESI) calcd for C20H14Cl2F3O3 [M
+ H]+ 429.0267, found 429.0274.
Methyl 5-(4-Bromobenzyl)-4-phenyl-2-(trifluoromethyl)furan-3-
carboxylate (3m). Oil (76 mg, 87% yield); 1H NMR (400 MHz,
CDCl3) δ 7.40 (d, J = 6.9 Hz, 5H), 7.25 (d, J = 6.7 Hz, 2H), 6.99 (d, J
= 7.8 Hz, 2H), 3.91 (s, 2H), 3.73 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 161.9, 152.2, 141.3 (q, J = 46.0 Hz), 135.6, 131.9, 131.0,
130.2, 129.7, 129.3, 128.4, 127.8, 124.1 (q, J = 286.0 Hz), 121.0, 117.4,
52.3, 31.7; 19F NMR (377 MHz, CDCl3) δ −62.10; HRMS (Q-TOF,
ESI) calcd for C20H15BrF3O3 [M + H]+ 439.0151, found 439.0153.
Methyl 5-(4-Iodobenzyl)-4-phenyl-2-(trifluoromethyl)furan-3-car-
boxylate (3n). Oil (91 mg, 94% yield); 1H NMR (400 MHz, CDCl3)
δ 7.52 (d, J = 8.3 Hz, 2H), 7.31 (d, J = 6.5 Hz, 3H), 7.16 (dd, J = 5.1,
2.6 Hz, 2H), 6.79 (t, J = 8.9 Hz, 2H), 3.82 (s, 2H), 3.65 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 161.9, 152.1, 141.4 (q, J = 41.0 Hz),
137.9, 136.3, 130.3, 129.7, 128.4, 128.5, 127.8, 124.1, 120.0 (q, J =
280.0 Hz), 117.4, 92.4, 52.4, 31.9; 19F NMR (377 MHz, CDCl3) δ
−62.10. HRMS (Q-TOF, ESI) calcd for C20H15F3IO3 [M + H]+
487.0012, found 487.0016.
(400 MHz, CDCl3) δ 7.56 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 7.9 Hz,
2H), 7.19 (t, J = 7.2 Hz, 2H), 7.14 (d, J = 7.0 Hz, 1H), 7.01 (d, J = 7.4
Hz, 2H), 3.85 (s, 2H), 3.64 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
160.5, 152.3, 141.0 (q, J = 42.0 Hz), 135.1, 133.2, 132.1, 129.4, 128.6,
128.4, 127.3, 127.2, 124.2 (q, J = 297.2 Hz), 121.6 (q, J = 245.9 Hz),
112.6, 51.2, 31.2; 19F NMR (377 MHz, CDCl3) δ −62.95, −62.70;
HRMS (Q-TOF, ESI) calcd for C21H15F6O3 [M + H]+ 429.0920,
found 429.0926.
Methyl 5-(2,3-Dichlorobenzyl)-4-(4-fluorophenyl)-2-
(trifluoromethyl)furan-3-carboxylate (3u). Oil (85 mg, 96% yield);
1H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 8.0 Hz, 1H), 7.23−7.16
(m, 2H), 7.07 (dt, J = 17.0, 8.1 Hz, 3H), 6.94 (d, J = 7.7 Hz, 1H), 4.11
(s, 2H), 3.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.0, 161.6 (q,
J = 220.8 Hz), 151.0, 141.0 (q, J = 42.9 Hz), 136.5, 133.6, 132.2, 131.4,
129.4, 128.3, 127.8, 127.4, 126.0, 124.0 (q, J = 201.4 Hz), 120.0, 115.6
(q, J = 21.7 Hz), 52.4, 31.1; 19F NMR (377 MHz, CDCl3) δ −61.89,
−113.28; HRMS (Q-TOF, ESI) calcd for C20H13Cl2F4O3 [M + H]+
447.0000, found 447.0179.
(E)-Methyl 3,5-Diphenyl-2-(2,2,2-trifluoro-1-hydroxyethylidene)-
penta-3,4-dienoate (7a). Known compound.11 1H NMR (400
MHz, CDCl3) δ 13.09 (s, 1H), 7.37−7.29 (m, 8H), 7.26−7.21 (m,
2H), 6.62 (s, 1H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
208.2, 172.9, 135.1, 133.2, 131.0, 128.9, 128.8, 128.3, 127.9, 127.6,
127.5, 126.0, 119.4 (q, J = 277.7 Hz), 102.3, 98.2, 53.3.
Methyl 3,5-Diphenyl-2-(2,2,2-trifluoroacetyl)penta-2,4-dienoate
(8a). Oil; 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 15.9 Hz,
1H), 7.39−7.36 (m, 2H), 7.31 (dd, J = 5.0, 1.8 Hz, 3H), 7.25 (dd, J =
5.0, 1.8 Hz, 3H), 7.11 (dd, J = 7.4, 1.8 Hz, 2H), 6.49 (d, J = 15.9 Hz,
1H), 3.77 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 185.1 (q, J = 37
Hz), 163.2, 159.7, 145.8, 135.7, 135.3, 130.2, 129.5, 129.2, 128.9,
128.8, 128.3, 126.1, 124.1, 116.7 (q, J = 290 Hz), 52.4; HRMS (Q-
TOF, ESI) calcd for C20H15F3O3 [M + H]+ 361.0973, found 361.0972.
Mixture of 3a and 8a. 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J =
15.9 Hz, 1.1H), 7.39−7.36 (m, 5.16H), 7.30 (m, 5.46H), 7.27−7.21
(m, 5.41H), 7.16 (s, 2.41H), 7.10 (dd, J = 7.5, 1.8 Hz, 2.19H), 7.03 (d,
J = 7.0 Hz, 0.68H), 6.49 (dd, J = 15.7, 13.3 Hz, 1.79H), 3.87 (s,
0.61H), 3.77 (s, 3H), 3.63 (s, 0.93H), 3.45 (s, 1.13H).
(E)-Dimethyl 2-(3-Phenylprop-2-ynyloxy)maleate (E-5a). Known
compound.9b White solid; 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J =
9.4 Hz, 2H), 7.24 (d, J = 6.9 Hz, 3H), 6.31 (s, 1H), 5.07 (s, 2H), 3.77
(s, 3H), 3.68 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.3, 163.0,
151.8, 131.5, 128.6, 128.1, 121.8, 110.9, 88.7, 82.6, 60.8, 52.7, 51.5.
(Z)-Dimethyl 2-(3-Phenylprop-2-ynyloxy)maleate (Z-5a). Known
compound.9b White solid; 1H NMR (400 MHz, acetone-d6) δ 7.44 (d,
J = 7.2 Hz, 2H), 7.34 (d, J = 6.5 Hz, 3H), 5.48 (s, 1H), 4.88 (s, 2H),
3.85 (s, 3H), 3.68 (s, 3H); 13C NMR (100 MHz, acetone-d6) δ 165.3,
162.8, 159.8, 131.2, 128.6, 127.9, 121.1, 94.1, 88.2, 80.6, 57.8, 52.1,
50.8.
Methyl 5-(Naphthalen-1-ylmethyl)-4-phenyl-2-(trifluoromethyl)-
1
furan-3-carboxylate (3o). Oil (75 mg, 91% yield); H NMR (400
MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.3 Hz, 2H),
7.47−7.34 (m, 6H), 7.27 (dd, J = 6.5, 3.1 Hz, 2H), 7.14 (d, J = 7.0 Hz,
1H), 4.40 (s, 2H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
162.1, 152.8, 141.2 (q, J = 42.0 Hz), 134.2, 133.6, 132.4, 130.5, 129.8,
128.5, 128.3, 127.8, 127.7, 127.0, 126.6, 126.4, 125.9, 124.1, 120.0 (q, J
= 267.0 Hz), 52.4, 32.5; 19F NMR (377 MHz, CDCl3) δ −61.90;
HRMS (Q-TOF, ESI) calcd for C24H18F3O3 [M + H]+ 411.1203,
found 411.1209.
Methyl 5-(Naphthalen-2-ylmethyl)-4-phenyl-2-(trifluoromethyl)-
1
furan-3-carboxylate (3p). Oil (63 mg, 77% yield); H NMR (400
MHz, CDCl3) δ 7.75−7.62 (m, 3H), 7.45 (s, 1H), 7.34 (m, J = 20.3,
7.6, 2.4 Hz, 5H), 7.18 (m, J = 21.8, 8.2, 2.0 Hz, 3H), 4.03 (s, 2H), 3.65
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.1, 152.8, 141.2 (q, J =
44.0 Hz), 134.2, 133.6, 132.4, 130.5, 129.8, 128.5, 128.3, 127.8, 127.7,
127.0, 126.6, 126.4, 125.9, 124.1, 120.0 (q, J = 280.9 Hz), 52.4, 32.5;
19F NMR (377 MHz, CDCl3) δ −62.10; HRMS (Q-TOF, ESI) calcd
for C24H18F3O3 [M + H]+ 411.1203, found 411.1207.
Methyl 5-Benzyl-4-(o-tolyl)-2-(trifluoromethyl)furan-3-carboxy-
1
late (3q). Oil (57 mg, 76% yield); H NMR (400 MHz, CDCl3) δ
7.31−7.18 (m, 6H), 7.11 (d, J = 7.5 Hz, 1H), 7.06 (d, J = 7.4 Hz, 2H),
3.81 (q, J = 5.7 Hz, 2H), 3.67 (s, 3H), 2.06 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 161.6, 152.9, 141.2 (q, J = 48.0 Hz) 137.8, 136.5,
130.4, 130.1, 130.0, 129.1, 128.7, 128.6, 127.8, 127.8, 126.9, 123.1,
2109
dx.doi.org/10.1021/jo4028424 | J. Org. Chem. 2014, 79, 2105−2110