Organic & Biomolecular Chemistry
Paper
+
the reaction mixture was subjected to the purification outlined calculated for [M + H] (C13
H
8
F
5
O) requires m/z 275.0490,
in the General procedure (silica gel, 20–80% Et O in petroleum found m/z 275.0490.
2
ether) to afford the title compound as a yellow solid (33 mg,
3q: 3′,4′,5′-Trifluoro-3-methoxy-[1,1′-biphenyl]-4-ol. Prepared
8
1
3%). νmax (solid): 3107, 2926, 2855, 1616, 1569, 1588, according to General procedure B using 5-bromo-2-methoxy-
374 cm− . H NMR (CD CN, 500 MHz): δ 7.79 (s, 1H), 7.72 phenylboronic acid MIDA ester (85 mg, 0.25 mmol, 1 equiv.),
1
1
3
(
6
(
s, 1H), 7.19 (t, J = 8.0 Hz, 1H), 7.03 (td, J = 7.6, 1.4 Hz, 1H), 4,4,5,5-tetramethyl-2-(3,4,5-trifluorophenyl)-1,3,2-dioxaboro-
.98–6.96 (m, 1H), 6.94 (br. s., 1H), 6.74–6.61 (m, 1H), 3.87 lane (97 mg, 0.375 mmol, 1.5 equiv.), Pd(OAc) (2.3 mg,
s, 3H). C NMR (DMSO-d , 126 MHz): δ 157.7, 135.9, 133.8, 0.01 mmol, 4 mol%), SPhos (8.2 mg, 0.02 mmol, 8 mol%),
2
1
3
6
1
29.7, 127.6, 122.0, 115.9, 113.0, 111.8, 38.6. HRMS: exact
K
3
PO
O) requires m/z (22.5 µL, 1.25 mmol, 5 equiv.), and 30 wt% aq. H
2.5 mmol, 10 equiv.). After 27 h, the reaction mixture was sub-
o: 2-Fluoro-4-(furan-3-yl)phenol. Prepared according to jected to the purification outlined in the General procedure
4
(159 mg, 0.75 mmol, 3 equiv.), THF (1 mL, 0.25 M), H
2
O
+
mass calculated for [M + H] (C10
75.0866, found m/z 175.0864.
H
11
N
2
2 2
O
(195 µL,
1
3
General procedure A using 4-bromo-2-fluorophenylboronic (silica gel, 5–20% EtOAc in petroleum ether) to afford the title
acid MIDA ester (83 mg, 0.25 mmol, 1 equiv.), 2-(furan-3-yl)- compound as an off-white solid (41 mg, 65%). νmax (film):
4
1
,4,5,5-tetramethyl-1,3,2-dioxaborolane (73 mg, 0.375 mmol, 3530, 2941, 2361, 1503, 1263, 1231, 1211, 1136, 1038,
2 3
.5 equiv.), Pd(dppf)Cl , 400 MHz): δ 7.17–7.12 (m, 2H),
·DCM (8.2 mg, 0.01 mmol, 4 mol%), 1022 cm− . H NMR (CDCl
1
1
K PO (159 mg, 0.75 mmol, 3 equiv.), THF (1 mL, 0.25 M), H O 7.10 (d, J = 2.5 Hz, 1H), 7.01 (dd, J = 8.1, 2.5 Hz, 1H), 6.93 (d,
3
4
2
1
3
(
2
2 2 3
22.5 µL, 1.25 mmol, 5 equiv.), and 30 wt% aq. H O (195 µL, J = 8.1 Hz, 1H), 5.73 (br. s., 1H), 3.96 (s, 3H). C NMR (CDCl ,
.5 mmol, 10 equiv.). After 27 h, the reaction mixture was sub- 101 MHz): δ 151.5 (ddd, JC–F = 248.9 Hz, JC–F = 10.0 Hz,
jected to the purification outlined in the General procedure
silica gel, 0–10% EtOAc in petroleum ether) to afford the title 15.6 Hz), 137.1 (td, JC–F = 8.0 Hz, JC–F = 4.3 Hz), 131.8, 118.7,
1
2
3
1
2
JC–F = 4.1 Hz), 147.1, 146.2, 139.0 (dt, J
= 251.1 Hz, J
=
C–F
C–F
3
(
2
3
compound as off-white solid (32 mg, 72%). νmax (film): 3362, 113.2, 111.1, 110.7 (dd, JC–F = 15.8 Hz, JC–F = 6.0 Hz), 56.2.
1
9
1
1
1
1
520, 1497, 1279, 1250, 1231, 1155, 1117, 1086, 1049,
F NMR (CDCl , 376 MHz): δ −134.5 (d, J = 20.4 Hz, 2F),
3
016 cm−
.0 Hz, 1H), 7.48 (t, J = 1.7 Hz, 1H), 7.22 (dd, J = 11.5, 2.0 Hz, [M − H] (C13
H), 7.18 (ddd, J = 8.4, 2.1, 1.0 Hz, 1H), 7.07–6.99 (m, 1H), 6.64
1 1
.
3
H NMR (CDCl , 400 MHz): δ 7.67 (dd, J = 1.4, −163.6 (t, J = 20.4 Hz, 1F). HRMS: exact mass calculated for
−
8 3 2
H F O ) requires m/z 253.0482, found m/z 253.0477.
3r: 2-(1-Methyl-1H-pyrazol-4-yl)phenol. Prepared according
to General procedure A using 2-bromophenylboronic acid
MIDA ester (70.6 mg, 0.226 mmol, 1 equiv.), 1-methyl-4-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (71.2 mg,
1
3
(
3
dd, J = 1.8, 0.9 Hz, 1H), 5.14 (br. s., 1H). C NMR (CDCl ,
01 MHz): δ 150.7 (d, JC–F = 237.0 Hz), 143.3, 141.9 (d, JC–F
3.5 Hz), 137.6, 125.4 (d, JC–F = 8.1 Hz), 124.9 (d, J
.7 Hz), 121.8 (d,
1
2
1
1
2
1
=
=
=
2
C–F
3
3
J
C–F = 5.4 Hz), 117.1, 112.6 (d,
J
C–F
0.339 mmol, 1.5 equiv.), Pd(dppf)Cl
2
·DCM (7.4 mg,
PO (144 mg, 0.678 mmol, 3 equiv.),
1
9
8.8 Hz), 108.3. F NMR (CDCl
3
, 376 MHz): δ −140.7 (s, 1F). 0.009 mmol, 4 mol%), K
3
4
+
HRMS: exact mass calculated for [M + H] (C H FO ) requires THF (0.9 mL, 0.25 M), H O (20 µL, 1.13 mmol, 5 equiv.), and
1
0
8
2
2
m/z 179.0503, found m/z 179.0502.
p:
pared according to General procedure B using 3-bromo-5- in the General procedure (silica gel, 20–80% Et O in petroleum
30 wt% aq. H
2
O
2
(177 µL, 2.26 mmol, 10 equiv.). After 27 h,
3
3-(2,4-Difluorophenyl)-5-(trifluoromethyl)phenol. Pre- the reaction mixture was subjected to the purification outlined
2
(
0
trifluoromethyl)phenylboronic acid MIDA ester (95 mg, ether) to afford the title compound as a yellow solid (30 mg,
−
1
.25 mmol, 1 equiv.), 4,4,5,5-tetramethyl-2-(2,4-difluorophe- 75%). νmax (solid): 3060, 2928, 2852, 1566, 1457, 1355 cm .
1
nyl)-1,3,2-dioxaborolane (90 mg, 0.375 mmol, 1.5 equiv.),
Pd(OAc) (2.3 mg, 0.01 mmol, 4 mol%), SPhos (8.2 mg, (dd, J = 7.7, 1.7 Hz, 1H), 7.20 (s, 1H), 7.05–7.11 (m, 1H),
.02 mmol, 8 mol%), K
THF (1 mL, 0.25 M), H O (22.5 µL, 1.25 mmol, 5 equiv.), and δ 153.0, 137.3, 129.4, 127.4, 127.0, 120.2, 119.8, 118.3, 115.8,
H NMR (CD CN, 500 MHz): δ 7.96 (s, 1H), 7.82 (s, 1H), 7.51
3
2
1
3
0
3 4 3
PO (159 mg, 0.75 mmol, 3 equiv.), 6.87–6.93 (m, 2H), 3.89 (s, 3H). C NMR (CD CN, 126 MHz):
2
+
3
0 wt% aq. H
reaction mixture was subjected to the purification outlined in requires m/z 175.0866, found m/z 175.0864.
the General procedure (silica gel, 0–20% Et O in petroleum 3s: 5-(3,6-Dihydro-2H-pyran-4-yl)-2-methoxyphenol. Pre-
ether) to afford the title compound as a brown solid (60 mg, pared according to General procedure B using (5-bromo-2-
8%). νmax (film): 3331, 1607, 1364, 1271, 1121, 1103 cm−1
methoxyphenyl)boronic acid MIDA ester (85 mg, 0.25 mmol,
H NMR (CDCl , 400 MHz): δ 7.43 (td, J = 8.7, 6.3 Hz, 1H), 7.34 1 equiv.), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-
2 2 11 2
O (195 µL, 2.5 mmol, 10 equiv.). After 27 h, the 38.3. HRMS: exact mass calculated for [M + H] (C10H N O)
2
8
.
1
3
(
(
(
s, 1H), 7.19 (d, J = 1.5 Hz, 1H), 7.14–7.11 (m, 1H), 7.03–6.92 dioxaborolane (79 mg, 0.375 mmol, 1.5 equiv.), Pd(OAc)
2
1
3
m, 2H), 5.30 (br. s, 1H). C NMR (CDCl
3
, 101 MHz): δ 162.8 (2.3 mg, 0.01 mmol, 4 mol%), SPhos (8.2 mg, 0.02 mmol,
1
3
1
dd, J
= 250.0 Hz, J
= 11.0 Hz), 159.7 (dd, J
= 250.0 8 mol%), K PO (159 mg, 0.75 mmol, 3 equiv.), THF (1 mL,
C–F
C–F
C–F 3 4
3
2
Hz, JC–F = 11.0 Hz), 155.8, 137.4, 132.4 (q, JC–F = 33.1 Hz), 0.25 M), H
1
2
O (22.5 µL, 1.25 mmol, 5 equiv.), and 30 wt% aq.
(195 µL, 2.5 mmol, 10 equiv.). After 27 h, the reaction
.4 Hz), 123.7 (q, JC–F = 272.1 Hz), 119.3, 118.2, 111.9 (dd, mixture was subjected to the purification outlined in the
3
2
31.4 (dd, JC–F = 7.5, 7.5 Hz), 123.6 (dd, JC–F = 13.5 Hz, JC–F
=
2 2
H O
1
5
2
2
J
C–F = 21.5 Hz, JC–F = 3.0 Hz), 111.7, 104.6 (dd, JC–F = 25.7, General procedure (silica gel, 10–20% EtOAc in petroleum
1
9
2
3
5.7 Hz). F NMR (CDCl , 376 MHz): δ −62.8 (s, 3F), −109.7 ether) to afford the title compound as an off-white solid
(d, J = 8.0 Hz, 1F), −113.1 (d, J = 8.0 Hz, 1F). HRMS: exact mass (35 mg, 67%). νmax (film): 3302, 2916, 1510, 1276, 1118, 1028,
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