The Journal of Organic Chemistry
Note
3
,5-Dimethyl-1-(4′-(trifluoromethyl)-[1,1′-biphenyl]-2-yl)-1H-pyr-
Hz), 137.6, 130.4, 129.9 (d, JC−F = 8.3 Hz), 129.3, 129.1, 128.9, 124.3
azole (2e). 3,5-Dimethyl-1-phenylpyrazole (86 mg, 0.5 mmol), 4-
(d, JC−F = 3.0 Hz), 115.5 (d, JC−F = 22.4 Hz), 114.3 (d, J
Hz), 105.8, 13.7, 11.2; FT-IR (neat, cm ) ν 1588, 1553, 1480, 1425,
= 21.1
C−F
−1
iodobenzotrifluoride (408 mg, 1.5 mmol), Pd(OAc) (5 mol %, 5.6
2
+
mg), silver oxide (140 mg, 0.6 mmol), LiOTf (94 mg, 0.6 mmol),
LiOAc (53 mg, 0.8 mmol), HFIP (0.38 mL), acetic acid (0.13 mL),
TFA (100 μL, 1.3 mmol), 130 °C for 48 h: pale yellow solid; mp 102−
03 °C (pentane); 81% yield (128 mg); purification (EtOAc/hexanes
1/8); R = 0.10 (EtOAc/hexanes = 1/8); H NMR (600 MHz,
CDCl ) δ 7.63−7.42 (m, 6H), 7.20 (d, J = 8.1 Hz, 2H), 5.78 (s, 1H),
.28 (s, 3H), 1.64 (s, 3H); C NMR (101 MHz, CDCl ) δ 149.0,
42.2 (q, JC−F = 1.4 Hz), 140.6, 137.9, 137.6, 130.5, 129.5, 129.5 (q,
JC−F = 32.4 Hz), 129.2, 129.2, 128.9, 125.4 (q, JC−F = 3.8 Hz), 124.3
1265, 1184, 1028; HRMS (ESI) calcd for C H FN Na [M + Na]
17
15
2
289.1111, found 289.1119.
1-(3′-Chloro-[1,1′-biphenyl]-2-yl)-3,5-dimethyl-1H-pyrazole (2j).
3,5-Dimethyl-1-phenylpyrazole (86 mg, 0.5 mmol), 3-chloroiodoben-
1
=
1
f
zene (358 mg, 1.5 mmol), Pd(OAc) (5 mol %, 5.6 mg), silver oxide
2
3
(93 mg, 0.4 mmol), LiOTf (94 mg, 0.6 mmol), LiOAc (53 mg, 0.8
mmol), HFIP (0.38 mL), acetic acid (0.13 mL), TFA (65 μL, 0.85
mmol), 120 °C for 72 h: pale yellow oil; 77% yield (109 mg);
13
2
1
3
purification (EtOAc/hexanes = 1/10); R = 0.20 (EtOAc/hexanes = 1/
f
−1
1
(
1
q, JC−F = 272.1 Hz), 106.0, 13.7, 11.3; FT-IR (neat, cm ) ν 1616,
557, 1494, 1405, 1368, 1321, 1158, 1070; HRMS (ESI) calcd for
8); H NMR (500 MHz, CDCl ) δ 7.55−7.42 (m, 4H), 7.22 (ddd, J =
8.0, 2.0, 1.2 Hz, 1H), 7.17 (t, J = 7.8 Hz, 1H), 7.10 (t, J = 1.9 Hz, 1H),
6.94 (dt, J = 7.6, 1.4 Hz, 1H), 5.79 (s, 1H), 2.29 (s, 3H), 1.65 (s, 3H);
3
+
C H F N [M + H] 317.1260, found 317.1262.
1
8
16
3
2
13
Ethyl 2′-(3,5-Dimethyl-1H-pyrazol-1-yl)-[1,1′-biphenyl]-4-carbox-
C NMR (126 MHz, CDCl ) δ 148.9, 140.7, 140.3, 138.0, 137.6,
3
ylate (2f). 3,5-Dimethyl-1-phenylpyrazole (86 mg, 0.5 mmol), ethyl 4-
1
34.2, 130.3, 129.6, 129.4, 129.1, 128.9, 128.6, 127.5, 126.7, 105.8,
iodobenzoate (414 mg, 1.5 mmol), Pd(OAc) (5 mol %, 5.6 mg),
silver oxide (93 mg, 0.4 mmol), LiOTf (94 mg, 0.6 mmol), LiOAc (53
mg, 0.8 mmol), HFIP (0.38 mL), acetic acid (0.13 mL), TFA (65 μL,
.85 mmol), 120 °C for 72 h: pale yellow oil; 80% yield (128 mg);
purification (EtOAc/hexanes = 1/5); R = 0.09 (EtOAc/hexanes = 1/
); H NMR (600 MHz, CDCl ) δ 7.93 (d, J = 8.4 Hz, 2H), 7.50
ddd, J = 20.5, 4.1, 1.5 Hz, 4H), 7.16 (d, J = 8.4 Hz, 2H), 5.75 (s, 1H),
.36 (q, J = 7.1 Hz, 2H), 2.28 (s, 3H), 1.38 (t, J = 7.1 Hz, 3H); 13
NMR (151 MHz, MeOD) δ 166.3, 148.9, 143.0, 141.4, 138.6, 136.9,
30.4, 129.7, 129.3, 129.2, 129.0, 128.8, 128.3, 105.7, 60.9, 13.2, 11.8,
.8; FT-IR (neat, cm ) ν 1713, 1609, 1554, 1492, 1366, 1271, 1183,
100, 1026; HRMS (ESI) calcd for C H N O [M + H] 321.1598,
found 321.1604.
−1
2
13.7, 11.3; FT-IR (neat, cm ) ν 1554, 1504, 1408, 1365, 1098, 1028;
HRMS (ESI) calcd for C H ClN Na [M + Na] 305.0816, found
+
17
15
2
3
05.0830.
0
1
-(3′,4′-Dimethyl-[1,1′-biphenyl]-2-yl)-3,5-dimethyl-1H-pyrazole
f
(2k). 3,5-Dimethyl-1-phenylpyrazole (86 mg, 0.5 mmol), 4-iodo-1,2-
1
8
(
4
3
dimethylbenzene (348 mg, 1.5 mmol), Pd(OAc) (5 mol %, 5.6 mg),
2
silver oxide (93 mg, 0.4 mmol), LiOTf (94 mg, 0.6 mmol), LiOAc (53
mg, 0.8 mmol), HFIP (0.38 mL), acetic acid (0.13 mL), TFA (65 μL,
C
0
.85 mmol), 120 °C for 24 h: yellow oil; 83% yield (115 mg);
1
9
1
purification (EtOAc/hexanes = 1/10); R = 0.20 (EtOAc/hexanes = 1/
f
−1
1
8
); H NMR (400 MHz, CDCl ) δ 7.61−7.36 (m, 4H), 7.01 (d, J =
3
+
20
21
2
2
7.8 Hz, 1H), 6.84 (s, 1H), 6.80 (dd, J = 7.8, 1.8 Hz, 1H), 5.76 (s, 1H),
2.30 (s, 3H), 2.23 (s, 3H), 2.16 (s, 3H), 1.61 (s, 3H); 13C NMR (101
1
-(2′-(3,5-Dimethyl-1H-pyrazol-1-yl)-[1,1′-biphenyl]-4-yl)ethan-
MHz, CDCl ) δ 148.6, 141.0, 139.4, 137.3, 136.6, 135.9, 135.9, 130.5,
3
1
-one (2g). 3,5-Dimethyl-1-phenylpyrazole (86 mg, 0.5 mmol), 4-
1
29.7, 129.3, 128.9, 128.0, 125.8, 122.5, 105.5, 19.8, 19.6, 13.6, 11.3;
iodoacetophenone (369 mg, 1.5 mmol), Pd(OAc) (5 mol %, 5.6 mg),
silver oxide (93 mg, 0.4 mmol), LiOTf (94 mg, 0.6 mmol), LiOAc (53
mg, 0.8 mmol), HFIP (0.38 mL), acetic acid (0.13 mL), TFA (65 μL,
.85 mmol), 120 °C for 72 h: pale yellow solid; mp 90−91 °C (diethyl
ether); 66% yield (96 mg); purification (EtOAc/hexanes = 1/5); R =
.05 (EtOAc/hexanes = 1/8); H NMR (600 MHz, CDCl ) δ 7.85 (d,
J = 8.3 Hz, 2H), 7.57−7.45 (m, 4H), 7.18 (d, J = 8.3 Hz, 2H), 5.76 (s,
H), 2.58 (s, 3H), 2.28 (s, 3H), 1.62 (s, 3H); 13C NMR (151 MHz,
CDCl ) δ 198.0, 149.0, 143.5, 140.6, 138.1, 137.6, 135.8, 130.4, 129.4,
29.2, 129.2, 128.8, 128.5, 105.9, 26.8, 13.7, 11.3; FT-IR (neat, cm )
ν 1716, 1687, 1489, 1359, 1268, 1183, 1103, 1027; HRMS (ESI) calcd
−1
2
FT-IR (neat, cm ) ν 1576, 1492, 1348, 1160, 1136, 1101; HRMS
+
(ESI) calcd for C H N Na [M + Na] 299.1519, found 299.1526.
19 20 2
1
-(4′,5-Dimethyl-[1,1′-biphenyl]-2-yl)-3,5-dimethyl-1H-pyrazole
0
(2l). 3,5-Dimethyl-1-(p-tolyl)pyrazole (93 mg, 0.5 mmol), 4-
f
iodotoluene (327 mg, 1.5 mmol), Pd(OAc) (5 mol %, 5.6 mg),
2
1
0
silver oxide (93 mg, 0.4 mmol), LiOTf (94 mg, 0.6 mmol), LiOAc (53
mg, 0.8 mmol), HFIP (0.38 mL), acetic acid (0.13 mL), TFA (65 μL,
0.85 mmol), 120 °C for 36 h: pale yellow oil; 83% yield (115 mg);
3
1
3
purification (EtOAc/hexanes = 1/10); R = 0.22 (EtOAc/hexanes = 1/
f
−1
1
1
8); H NMR (600 MHz, CDCl ) δ 7.32 (d, J = 8.0 Hz, 1H), 7.29 (d, J
3
= 1.5 Hz, 1H), 7.22 (dd, J = 8.1, 1.7 Hz, 1H), 7.05 (d, J = 7.9 Hz, 2H),
6.97 (d, J = 8.1 Hz, 2H), 5.74 (s, 1H), 2.44 (s, 3H), 2.31 (s, 3H), 2.29
+
for C H N ONa [M + Na] 313.1311, found 313.1324.
19
18
2
(s, 3H), 1.60 (s, 3H); 13C NMR (151 MHz, CDCl ) δ 148.4, 140.7,
1
-(3′-Methoxy-[1,1′-biphenyl]-2-yl)-3,5-dimethyl-1H-pyrazole
2h). 3,5-Dimethyl-1-phenylpyrazole (86 mg, 0.5 mmol), 3-iodoanisole
351 mg, 1.5 mmol), Pd(OAc) (5 mol %, 5.6 mg), silver oxide (93
3
(
(
1
39.0, 138.8, 137.0, 135.8, 135.0, 131.0, 129.1, 128.7, 128.7, 128.4,
−1
2
105.3, 21.4, 21.3, 13.8, 11.3; FT-IR (neat, cm ) ν 2920, 1552, 1503,
1
2
mg, 0.4 mmol), LiOTf (94 mg, 0.6 mmol), LiOAc (53 mg, 0.8 mmol),
HFIP (0.38 mL), acetic acid (0.13 mL), TFA (65 μL, 0.85 mmol), 120
C for 36 h: pale yellow oil; 75% yield (104 mg); purification (EtOAc/
hexanes = 1/8); R = 0.15 (EtOAc/hexanes = 1/8); H NMR (400
MHz, CDCl ) δ 7.59−7.40 (m, 4H), 7.24−7.16 (m, 1H), 6.89−6.75
m, 2H), 6.53 (dd, J = 2.5, 1.7 Hz, 1H), 5.77 (s, 1H), 3.63 (s, 3H),
.29 (s, 3H), 1.62 (s, 3H); C NMR (151 MHz, CDCl ) δ 159.4,
48.6, 141.0, 139.9, 139.2, 137.6, 130.4, 129.4, 129.3, 129.0, 128.5,
21.0, 114.5, 112.7, 105.8, 55.1, 13.7, 11.2; FT-IR (neat, cm ) ν 1591,
469, 1417, 1367, 1216, 1181, 1022; HRMS (ESI) calcd for
C H N O [M + H] 279.1492, found 279.1501.
8
1
+
420, 1187, 1029; HRMS (ESI) calcd for C H N Na [M + Na]
19 20 2
99.1519, found 299.1529.
°
1
-(5-Methoxy-4′-methyl-[1,1′-biphenyl]-2-yl)-3,5-dimethyl-1H-
1
f
pyrazole (2m). 1-(4-Methoxyphenyl)-3,5-dimethylpyrazole (101 mg,
3
0.5 mmol), 4-iodotoluene (327 mg, 1.5 mmol), Pd(OAc) (5 mol %,
2
(
5.6 mg), silver oxide (93 mg, 0.4 mmol), LiOTf (94 mg, 0.6 mmol),
LiOAc (53 mg, 0.8 mmol), HFIP (0.38 mL), acetic acid (0.13 mL),
TFA (65 μL, 0.85 mmol), 120 °C for 36 h: pale yellow solid; mp 92−
13
2
1
1
1
3
−1
93 °C (pentane); 87% yield (127 mg); purification (EtOAc/hexanes =
1
1/5); R = 0.07 (EtOAc/hexanes = 1/8); H NMR (500 MHz,
f
+
1
19
2
CDCl ) δ 7.35 (d, J = 8.6 Hz, 1H), 7.06 (dd, J = 8.5, 0.6 Hz, 2H),
3
-(3′-Fluoro-[1,1′-biphenyl]-2-yl)-3,5-dimethyl-1H-pyrazole (2i).
7.01−6.97 (m, 3H), 6.93 (dd, J = 8.6, 2.9 Hz, 1H), 5.73 (s, 1H), 3.87
(s, 3H), 2.31 (s, 3H), 2.29 (s, 3H), 1.60 (s, 3H); 13C NMR (126 MHz,
3
,5-Dimethyl-1-phenylpyrazole (86 mg, 0.5 mmol), 3-fluoroiodoben-
zene (327 mg, 1.5 mmol), Pd(OAc) (5 mol %, 5.6 mg), silver oxide
93 mg, 0.4 mmol), LiOTf (94 mg, 0.6 mmol), LiOAc (53 mg, 0.8
2
CDCl ) δ 159.8, 148.3, 140.9, 140.5, 137.3, 135.7, 130.6, 130.1, 129.2,
3
−1
(
128.3, 115.2, 113.3, 105.2, 55.7, 21.3, 13.8, 11.2; FT-IR (neat, cm ) ν
mmol), HFIP (0.38 mL), acetic acid (0.13 mL), TFA (65 μL, 0.85
mmol), 120 °C for 72 h: pale yellow oil; 80% yield (107 mg);
1609, 1553, 1495, 1421, 1292, 1207, 1029; HRMS (ESI) calcd for
+
C H N O [M + H] 293.1648, found 293.1655.
19
21
2
purification (EtOAc/hexanes = 1/10); R = 0.17 (EtOAc/hexanes = 1/
3,5-Dimethyl-1-(4′-methyl-5-(trifluoromethyl)-[1,1′-biphenyl]-2-
f
1
8
8
1
2
1
); H NMR (500 MHz, CDCl ) δ 7.57−7.40 (m, 4H), 7.21 (td, J =
yl)-1H-pyrazole (2n). 3,5-Dimethyl-1-(4-(trifluoromethyl)phenyl)-
3
.0, 6.0 Hz, 1H), 6.94 (tdd, J = 8.4, 2.6, 0.9 Hz, 1H), 6.88 (ddd, J = 7.7,
.6, 0.9 Hz, 1H), 6.79 (ddd, J = 10.3, 2.6, 1.6 Hz, 1H), 5.78 (s, 1H),
pyrazole (120 mg, 0.5 mmol), 4-iodotoluene (327 mg, 1.5 mmol),
Pd(OAc) (5 mol %, 5.6 mg), silver oxide (93 mg, 0.4 mmol), LiOAc
2
.28 (s, 3H), 1.65 (d, J = 0.7 Hz, 3H); 13C NMR (126 MHz, CDCl ) δ
(53 mg, 0.8 mmol), LiOTf (94 mg, 0.6 mmol), HFIP (0.38 mL),
acetic acid (0.13 mL), TFA (65 μL, 0.85 mmol), 120 °C for 84 h: pale
3
62.7 (d, JC−F = 245.4 Hz), 148.9, 140.7, 140.7, 138.1 (d, JC−F = 2.2
D
J. Org. Chem. XXXX, XXX, XXX−XXX