The Journal of Organic Chemistry
Article
5-Methoxy-3-phenyl-1-naphthol 19d. 1-Naphthol 19d was
prepared from 2-(2-methoxyphenyl)acetic acid 15d (16.618 g,
100.07 mmol) using the general procedure A1. The crude product
was purified by recrystallization from dichloromethane/hexanes and
column chromatography (silica gel, dichloromethane/hexanes: 1:3 to
1:1) to give 19d as a white crystal in 52% isolated yield from 15d
(13.042 g, mp 142−143 °C, 52.036 mmol). Spectral data for 19d: Rf
the joint and Teflon tape wrapped around the joint to secure a tight
seal. The reaction mixture was heated and stirred in a 190 °C oil bath
for 48 h with a gentle nitrogen flow across the top of the condenser.
The brown reaction mixture is cooled to about 60 °C (oil bath
temperature), and an aqueous solution of potassium hydroxide (33.4
g, 0.600 mol, 6.00 equiv) in 120 mL of water is slowly added. After
stirring in a 100 °C oil bath overnight (12 h), the orange solution is
cooled to room temperature; diethyl ether (300 mL) is added, and
the mixture stirred for 30 min before the organic layer is isolated in a
2 L separatory funnel. The water layer is extracted twice with diethyl
ether (300 mL× 2), and the combined organic layer is washed with
brine (300 mL), dried over anhydrous magnesium sulfate and filtered.
The dark-colored organic solution is concentrated in vacuo using a
rotary evaporator (40 °C, 15 mmHg) and the residue is dried under
high vacuum (23 °C, 0.2 mmHg) overnight to give 40 g of the dark
brown crude product. Recrystallization from dichloromethane/
hexanes and column chromatography (silica gel, dichloromethane/
hexanes: 1:3 to 1:1) gave the product 21a as an off-white solid
(15.2948 g, mp 117−120 °C, 61.8942 mmol) in a yield of 62% from
1
= 0.42 (ethyl acetate/hexanes 1:4); H NMR (500 MHz, CDCl3) δ
4.00 (s, 3H), 6.86 (dd, J = 7.7, 0.9 Hz, 1H), 7.12 (d, J = 1.6 Hz, 1H),
7.27−7.52 (m, 4H), 7.70 (ddt, J = 10.6, 7.8, 1.0 Hz, 3H), 8.07 (dd, J =
1.7, 0.9 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3) δ 55.6, 104.8,
109.0, 113.0, 113.5, 124.4, 125.4, 127.1, 127.3, 127.3, 128.7, 138.1,
141.1, 151.5, 155.7. HRMS (ESI−) m/z: [M − H]− Calcd for
C17H13O2 249.0916; Found 249.0937.
5,5′-OMe2VANOL 12d. VANOL derivative 12d was prepared from
5-methoxy-3-phenyl-1-naphthol 19d (12.520 g, 50.263 mmol) using
the general procedure B with heating at 165 °C for 24 h. The crude
product was purified by recrystallization from dichloromethane/
hexanes and column chromatography (silica gel, dichloromethane/
hexanes: 1:3 to 1:1) to give 12d as an off-white solid in 72% isolated
yield (8.9962 g, mp >260 °C 19.340 mmol). Spectral data for 12d: 1H
NMR (500 MHz, CDCl3) δ 3.97 (s, 6H), 5.78 (s, 2H), 6.67 (d, J =
7.5 Hz, 4H), 6.90 (d, J = 7.8 Hz, 2H), 6.93−7.00 (m, 4H), 7.02−7.11
(m, 2H), 7.42−7.50 (m, 2H), 7.74 (s, 2H), 7.91 (d, J = 8.4 Hz, 2H).
13C{1H} NMR (126 MHz, CDCl3) δ 55.5, 105.3, 113.4, 114.8, 116.2,
123.8, 125.7, 126.4, 126.7, 127.4, 128.9, 139.9, 140.5, 150.1, 155.3.
HRMS (ESI−) m/z: [M − H]− Calcd for C34H25O2 465.1655; Found
465.1649.
1
phenylacetyl chloride. Spectral data for 21a: H NMR (500 MHz,
CDCl3) δ 1.28 (t, J = 7.6, 3H), 2.70 (q, J = 7.6 Hz, 2H), 5.26 (s, 1H),
7.07 (d, J = 1.7 Hz, 1H), 7.26−7.35 (m, 2H), 7.48 (dddd, J = 18.0,
8.1, 6.8, 1.4 Hz, 2H), 7.56−7.68 (m, 3H), 7.79−7.89 (m, 1H), 8.15
(ddd, J = 8.0, 1.6, 0.8 Hz, 1H). 13C{ 1H} NMR (126 MHz, CDCl3) δ
15.6, 28.5, 108.4, 118.5, 121.4, 123.4, 125.2, 126.8, 127.2, 128.0,
128.4, 135.0, 138.2, 138.8, 143.7, 151.6. HRMS (ESI−) m/z: [M −
H]− Calcd for C18H 15O 247.1123; Found 247.1138.
3,3′-pEtPh2VANOL 11a (Scheme 4). VANOL derivative 11a was
prepared from 3-(4-ethylphenyl)-1-naphthol 21a (12.416 g, 50.244
mmol) using the general procedure B with heating at 165 °C for 36 h.
The crude product was purified by recrystallization from dichloro-
methane/hexanes and column chromatography (silica gel, dichloro-
methane/hexanes: 1:3 to 1:1) to give 11a as an off-white solid in 63%
isolated yield (7.823 g, mp 178−180 °C, 15.86 mmol). Spectral data
for 11a: 1H NMR (500 MHz, CDCl3) δ 1.15 (td, J = 7.6, 0.9 Hz, 6H),
2.51 (q, J = 7.6 Hz, 4H), 5.79 (d, J = 1.1 Hz, 2H), 6.51−6.63 (m,
4H), 6.79 (d, J = 8.0 Hz, 4H), 7.34 (s, 2H), 7.47−7.61 (m, 4H),
7.73−7.84 (m, 2H), 8.34 (ddd, J = 7.4, 2.2, 0.9 Hz, 2H). 13C{1H}
NMR (126 MHz CDCl3) δ 15.6, 28.4, 112.8, 121.9, 122.8, 122.8,
125.4, 127.0, 127.4, 127.6, 128.7, 134.6, 137.5, 140.7, 142.6, 150.2.
HRMS (ESI−) m/z: [M − H]− Calcd for C36H29O2 493.2168; Found
493.2176.
3-(4-Methoxyphenyl)-1-naphthol 21b (Scheme 4). 1-Naphthol
21b was prepared from 4-ethynylanisole 20b (17.2 mL, 130 mmol)
using the general procedure A3. The crude product was purified by
recrystallization from dichloromethane/hexanes and column chroma-
tography (silica gel, dichloromethane/hexanes: 1:3 to 1:1) to give 21b
as an off-white crystal in 47% isolated yield from phenylacetal chloride
(11.8537 g, mp 155−156 °C, 47.5877 mmol). Spectral data for 21b:
1H NMR (500 MHz, CDCl3) δ 3.85 (s, 3H), 5.29 (s, 1H), 6.96−7.02
(m, 2H), 7.03−7.06 (m, 1H), 7.47 (dddd, J = 20.2, 8.1, 6.8, 1.4 Hz,
2H), 7.57−7.64 (m, 3H), 7.80−7.86 (m, 1H), 8.14 (ddd, J = 8.2, 1.5,
0.8 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3) δ 55.4, 108.2, 114.3,
118.0, 121.4, 123.2, 125.0, 126.8, 127.9, 128.3, 133.4, 135.0, 138.5,
151.6, 159.3. HRMS (ESI−) m/z: [M − H]− Calcd for C17H13O
249.0916; Found 249.0937. These spectral data match those
previously reported for this compound.16
5-Trifluoromethyl-3-phenyl-1-naphthol 19e. 1-Naphthol 19e was
prepared from 2-(2-trifluoromethylphenyl)acetic acid 15e (20.42 mL,
100.0 mmol) using the general procedure A1. The crude product was
purified by recrystallization from dichloromethane/hexanes and
column chromatography (silica gel, dichloromethane/hexanes: 1:3
to 1:1) to give 19e as a white crystal in 66% isolated yield from 15e
(19.206 g, mp 122−123 °C, 66.904 mmol). Spectral data for 19e: Rf
1
= 0.48 (ethyl acetate/hexanes 1:4); H NMR (500 MHz, CDCl3) δ
5.46 (s, 1H), 7.14 (d, J = 1.4 Hz, 1H), 7.32−7.55 (m, 4H), 7.61−7.73
(m, 2H), 7.78−8.03 (m, 2H), 8.43 (d, J = 8.4 Hz, 1H). 13C{1H}
NMR (126 MHz, CDCl3) δ 109.1, 115.2, 115.2, 123.5, 124.2, 125.8
(q, J = 5 Hz), 125.9, 126.5, 127.5, 127.9, 129.0, 130.5, 140.6, 140.8,
152. HRMS (ESI−) m/z: [M − H]− Calcd for C17H10F3O 287.0684;
Found 287.0682.
5,5′-(CF3)2VANOL 12e. VANOL derivative 12e was prepared from
5-trifluoromethyl-3-phenyl-1-naphthol 19e (14.41, 50.20 mmol) using
the general procedure B with heating at 165 °C for 24 h. The crude
product was purified by recrystallization from dichloromethane/
hexanes and column chromatography (silica gel, dichloromethane/
hexanes: 1:3 to 1:1) to give 12e as an off-white solid in 65% isolated
yield (9.382 g, mp >260 °C, 16.37 mmol). Spectral data for 12e: Rf =
0.32 (dichloromethane/hexanes 1:1); 1H NMR (500 MHz, CDCl3) δ
5.84 (d, J = 18.0 Hz, 2H), 6.58−6.71 (m, 4H), 7.00 (td, J = 7.8, 2.8
Hz, 4H), 7.06−7.18 (m, 2H), 7.54−7.68 (m, 4H), 7.96 (d, J = 7.2 Hz,
2H), 8.58 (d, J = 8.4 Hz, 2H). 13C{1H} NMR (126 MHz, CDCl3) δ
113.1, 113.2, 118.5, 123.5, 123.6, 124.1, 125.6, 125.8, 126.1, 126.4,
126.4, 126.5, 126.5, 127.2, 127.4, 127.7, 128.8, 130.3, 139.5, 139.6,
142.3, 150.7, 150.7. 19F NMR (470 MHz, CDCl3) δ −59.76 (s).
HRMS (ESI−) m/z: [M − H]− Calcd for C34H19F6O2 573.1289;
Found 573.1265.
3,3′-pOMePh2VANOL 11b (Scheme 4). VANOL derivative 11b
was prepared from 5-methoxy-3-phenylnaphthalen-1-ol 21b (11.264
g, 45.220 mmol, 1.00 equiv) using the general procedure B with
heating at 165 °C for 36 h. The crude product was purified by
recrystallization from dichloromethane/hexanes and column chroma-
tography (silica gel, dichloromethane/hexanes: 1:3 to 1:1) to give 11b
as an off-white solid in 68% (76% brsm) isolated yield (7.6002 g, mp
Synthesis of 3,3′-R2VANOL Ligands (Scheme 4). General
procedure A3 for the CEC process with 2-phenylacetyl chloride,
illustrated for the synthesis the of 3-(4-ethylphenyl)-1-naphthol 21a
with 1-ethyl-4-ethynylbenzene.
3-(4-Ethylphenyl)-1-naphthol 21a (Scheme 4). An oven-dried
500 mL round-bottomed flask equipped with an egg-shaped stirring
bar (30 × 15 mm) and a condenser is placed under a nitrogen
atmosphere through a gas inlet. After cooling to 23 °C, 2-phenylacetyl
chloride (13.22 mL, 100.0 mmol, 1.000 equiv) is added followed by 1-
ethyl-4-ethynylbenzene 20a (18.2 mL, 130 mmol, 1.30 equiv) and
isobutyric anhydride (33.0 mL, 200 mmol, 2.00 equiv). The flask is
fitted with a condenser flushed with nitrogen with a Teflon sleeve in
1
243−244 °C, 15.287 mmol). Spectral data for 11b: H NMR (500
MHz, CDCl3) δ 3.68 (s, 6H), 5.79 (s, 2H), 6.51 (d, J = 9.8 Hz, 4H),
6.61 (d, J = 8.3 Hz, 4H), 7.30 (s, 2H), 7.45−7.58 (m, 4H), 7.77 (d, J
= 7.1 Hz, 2H), 8.32 (d, J = 7.8 Hz, 2H). 13C{1H} NMR (126 MHz,
CDCl3) δ 55.1, 112.9, 112.9, 121.8, 122.7, 122.8, 125.4, 127.4, 127.6,
K
J. Org. Chem. XXXX, XXX, XXX−XXX