The Journal of Organic Chemistry
Note
Hz, J2 = 7.3 Hz, J3 = 1.8 Hz, 1H), 6.96 (t, J = 7.5 Hz, 1H), 6.93 (d, J =
8.5 Hz, 1H), 4.56 (tt, J1 = 8.0 Hz, J2 = 4.0 Hz, 1H), 2.07−1.87 (m,
4H), 1.83−1.76 (m, 2H), 1.74−1.47 (m, 8H). 13C NMR (125 MHz,
CDCl3) δ 190.4, 160.6, 135.9, 128.4, 125.8, 120.3, 114.2, 78.9, 31.5,
27.2, 25.7, 23.0; HRMS (FAB+) m/z Calcd for C15H21O2 [M + H]+
233.1542, found 233.1541.
2-(((1r,3r,5r,7r)-Adamantan-2-yl)oxy)benzaldehyde (13h). The
title compound was prepared from 2-fluorobenzaldehyde (1.05 mL,
10.0 mmol) and 2-adamantanol (1.59 g, 10.5 mmol) according to the
general three-step procedure. Purification by silica gel column
chromatography (20:1 hexane:Et2O → 10:1 hexane:Et2O) provided
the product as a white solid (1.01 g, 40% yield). mp = 69−71 °C; 1H
NMR (500 MHz, CDCl3) δ 10.63 (d, J = 0.8 Hz, 1H), 7.84 (dd, J1 =
7.9 Hz, J2 = 1.9 Hz, 1H), 7.49 (ddd, J1 = 8.5 Hz, J2 = 7.3 Hz, J3 = 1.9
Hz, 1H), 6.99−6.95 (m, 2H), 4.58 (t, J = 3.2 Hz, 1H), 2.25−2.19 (m,
2H), 2.16−2.10 (m, 2H), 1.97−1.86 (m, 4H), 1.83−1.75 (m, 4H),
1.62−1.57 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 190.2, 160.4,
135.8, 128.5, 125.9, 120.3, 114.0, 80.2, 37.4, 36.4, 31.8, 31.7, 27.3, 27.2;
HRMS (EI+) m/z Calcd for C17H20O2 [M]+ 256.1463, found
256.1453.
2-(((1r,3r,5r,7r)-2-Methyladamantan-2-yl)oxy)benzaldehyde
(13o). The title compound was prepared from 2-fluorobenzaldehyde
(1.05 mL, 10.0 mmol) and 2-methyl-2-adamantanol (1.75 g, 10.5
mmol) according to the general three-step procedure. After the first
chromatographic purification on silica gel (100:1 hexane:Et2O → 20:1
hexane:Et2O), the product still contained unidentifiable impurities. A
second purification by silica gel column chromatography (10:1
hexane:DCM → 1:1 hexane:DCM) provided the product as a pale-
1
yellow solid (229 mg, 8% yield). mp = 38−40 °C; H NMR (500
MHz, CDCl3) δ 10.52 (d, J = 0.8 Hz, 1H), 7.84 (dd, J1 = 7.7 Hz, J2 =
1.9 Hz, 1H), 7.44 (ddd, J1 = 8.4 Hz, J2 = 7.2 Hz, J3 = 1.9 Hz, 1H), 7.08
(d, J = 8.4 Hz, 1H), 7.02 (ddt, J1 = 8.0 Hz, J2 = 7.3 Hz, J3 = 0.9 Hz,
1H), 2.36−2.30 (m, 2H), 2.26−2.21 (m, 2H), 1.95−1.81 (m, 6H),
1.77−1.73 (m, 2H), 1.65−1.59 (m, 2H), 1.45 (s, 3H); 13C NMR (125
MHz, CD2Cl2) δ 191.1, 160.1, 135.5, 129.2, 128.5, 121.7, 120.6, 86.8,
38.68, 38.66, 35.5, 33.5, 28.0, 27.5, 23.0; HRMS (FAB+) m/z Calcd
for C18H23O2 [M + H]+ 271.1698, found 271.1687.
2-(((1r,3r,5r,7r)-Adamantan-2-yl)oxy)-5-methoxybenzaldehyde
(13q). The title compound was prepared from 2-fluoro-5-methox-
ybenzaldehyde (1.24 mL, 10.0 mmol) and 2-adamantanol (1.59 g, 10.5
mmol) according to the general three-step procedure. Purification by
silica gel column chromatography (10:1 hexane:Et2O → 4:1
hexane:Et2O) provided the product as a white solid (1.44 g, 50%
2-((2,4-Dimethylpentan-3-yl)oxy)benzaldehyde (13i). The title
compound was prepared from 2-fluorobenzaldehyde (1.05 mL, 10.0
mmol) and 2,4-dimethyl-3-pentanol (1.47 mL, 10.5 mmol) according
to the general three-step procedure. Purification by silica gel column
chromatography (40:1 hexane:Et2O) provided the product as a yellow
1
yield). mp = 123−125 °C; H NMR (500 MHz, CDCl3) δ 10.58 (s,
1H), 7.32 (d, J = 3.0 Hz, 1H), 7.09 (dd, J1 = 9.0 Hz, J2 = 3.0 Hz, 1H),
6.93 (d, J = 9.0 Hz, 1H), 4.48 (t, J = 3.3 Hz, 1H), 3.79 (s, 3H), 2.21−
2.16 (m, 2H), 2.14−2.08 (m, 2H), 1.95−1.85 (m, 4H), 1.80−1.73 (m,
4H), 1.62−1.55 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 189.8,
155.3, 153.6, 126.4, 123.8, 116.3, 110.2, 81.2, 55.9, 37.5, 36.5, 31.9,
31.8, 27.4, 27.3; HRMS (FAB+) m/z Calcd for C18H22O3 [M]+
286.1569, found 286.1570.
1
oil (1.31 g, 59% yield). H NMR (500 MHz, CDCl3) δ 10.59 (d, J =
0.8 Hz, 1H), 7.81 (dd, J1 = 7.7 Hz, J2 = 1.9 Hz, 1H), 7.47 (ddd, J1 = 8.5
Hz, J2 = 7.2 Hz, J3 =1.9 Hz, 1H), 7.02 (d, J = 8.6 Hz, 1H), 6.93 (ddt, J1
= 8.0 Hz, J2 = 7.3 Hz, J3 = 0.9 Hz, 1H), 4.09 (t, J = 5.7 Hz, 1H), 2.15−
2.01 (m, 2H), 0.98 (d, J = 6.7 Hz, 6H), 0.95 (d, J = 6.8 Hz, 6H); 13C
NMR (125 MHz, CDCl3) δ 190.3, 163.5, 135.9, 128.5, 125.1, 112.0,
113.6, 88.2, 30.8, 20.2, 17.9; HRMS (FAB+) m/z Calcd for C14H21O2
[M + H]+ 221.1542, found 221.1530.
2-(Dicyclohexylmethoxy)benzaldehyde (13j). The title compound
was prepared from 2-fluorobenzaldehyde (1.05 mL, 10.0 mmol) and
dicyclohexylmethanol (2.06 g, 10.5 mmol) according to the general
three-step procedure. Purification by silica gel column chromatography
(40:1 hexane:Et2O) provided the product as a colorless oil (1.72 g,
57% yield). 1H NMR (500 MHz, CDCl3) δ 10.58 (d, J = 0.8 Hz, 1H),
7.81 (dd, J1 = 7.7 Hz, J2 = 1.7 Hz, 1H), 7.46 (ddd, J1 = 8.6 Hz, J2 = 7.2
Hz, J3 = 1.9 Hz, 1H), 7.00 (d, J = 8.7 Hz, 2H), 6.92 (ddt, J1 = 8.0 Hz, J2
= 7.3 Hz, J3 = 0.9 Hz, 1H), 4.11 (t, J = 5.6 Hz, 1H), 1.86−1.69 (m,
8H), 1.69−1.60 (m, 4H), 1.31−1.05 (m, 10H); 13C NMR (125 MHz,
CDCl3) δ 190.4, 163.7, 135.9, 128.5, 125.0, 119.9, 113.6, 87.1, 40.0,
30.6, 28.3, 26.53, 26.48, 26.3; HRMS (FAB+) m/z Calcd for C20H29O2
[M + H]+ 301.2168, found 301.2179.
2-(((1r,3r,5r,7r)-Adamantan-2-yl)oxy)-5-methylbenzaldehyde
(13r). The title compound was prepared from 2-fluoro-5-methyl-
benzaldehyde (1.22 mL, 10.0 mmol) and 2-adamantanol (1.59 g, 10.5
mmol) according to the general three-step procedure. Purification by
silica gel column chromatography (20:1 hexane:Et2O → 10:1
hexane:Et2O) provided the product as a white solid (1.52 g, 56%
yield). mp = 90−93 °C; 1H NMR (500 MHz, CDCl3) δ 10.59 (s, 1H),
7.63 (d, J = 2.2 Hz, 1H), 7.29 (ddd, J1 = 8.5 Hz, J2 = 2.4 Hz, J3 = 0.8
Hz, 1H), 6.87 (d, J = 8.5 Hz, 1H), 4.53 (t, J = 3.4 Hz, 1H), 2.29 (s,
3H), 2.23−2.17 (m, 2H), 2.14−2.09 (m, 2H), 1.95−1.84 (m, 4H),
1.81−1.74 (m, 4H), 1.60−1.53 (m, 2H); 13C NMR (125 MHz,
CDCl3) δ 190.2, 158.5, 136.5, 129.8, 128.4, 125.7, 114.2, 80.4, 37.5,
36.5, 31.79, 31.77, 27.34, 27.27, 20.3; HRMS (FAB+) m/z Calcd for
C18H23O2 [M + H]+ 271.1698, found 271.1694.
2-(((1r,3r,5r,7r)-Adamantan-2-yl)oxy)-5-chlorobenzaldehyde
(13s). The title compound was prepared from 5-chloro-2-fluoroben-
zaldehyde (1.59 g, 10.0 mmol) and 2-adamantanol (1.59 g, 10.5
mmol) according to the general three-step procedure. Purification by
silica gel column chromatography (10:1 hexane:Et2O) provided the
product as a pale-yellow solid (1.96 g, 67% yield). mp = 136−139 °C;
1H NMR (500 MHz, CDCl3) δ 10.54 (s, 1H), 7.78 (d, J = 2.8 Hz,
2-(tert-Butoxy)benzaldehyde (13m). The title compound was
prepared from 2-fluorobenzaldehyde (1.05 mL, 10.0 mmol) and
sodium tert-butoxide (1.01 g, 10.5 mmol) according to the general
three-step procedure. Purification by silica gel column chromatography
(40:1 hexane:Et2O → 20:1 hexane:Et2O) provided the product as a
1
colorless oil (465 mg, 26% yield). H NMR (500 MHz, CDCl3) δ
1H), 7.43 (dd, J1 = 8.9 Hz, J2 = 2.8 Hz, 1H), 6.93 (d, J = 9.0 Hz, 1H),
4.55 (t, J = 3.5 Hz, 1H), 2.24−2.17 (m, 2H), 2.12−2.06 (m, 2H),
1.97−1.86 (m, 4H), 1.82−1.75 (m, 4H), 1.63−1.56 (m, 2H); 13C
NMR (125 MHz, CDCl3) δ 188.7, 158.9, 135.3, 128.2, 126.9, 126.1,
115.8, 81.1, 37.4, 36.5, 31.80, 31.76, 27.3, 27.2; HRMS (FAB+) m/z
Calcd for C17H20ClO2 [M + H]+ 291.1152, found 291.1140.
10.45 (d, J = 0.8 Hz, 1H), 7.84 (ddd, J1 = 7.7 Hz, J2 = 1.9 Hz, J3 = 0.5
Hz, 1H), 7.50 (ddd, J1 = 8.3 Hz, J2 = 7.2 Hz, J3 = 1.9 Hz, 1H), 7.16−
7.08 (m, 2H), 1.44 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 191.0,
159.2, 135.0, 130.2, 128.1, 122.94, 122.91, 80.8, 29.1; HRMS (EI+) m/
z Calcd for C11H14O2 [M]+ 178.0994, found 178.0954.
2-(((1s,3s)-Adamantan-1-yl)oxy)benzaldehyde (13n). The title
compound was prepared from 2-fluorobenzaldehyde (1.05 mL, 10.0
mmol) and 1-adamantanol (1.59 g, 10.5 mmol) according to the
general three-step procedure. Purification by silica gel column
chromatography (40:1 hexane:Et2O) provided the product as an off-
2-(((1r,3r,5r,7r)-Adamantan-2-yl)oxy)-5-(trifluoromethyl)-
benzaldehyde (13t). The title compound was prepared from 2-fluoro-
5-(trifluoromethyl)benzaldehyde (1.41 mL, 10.0 mmol) and 2-
adamantanol (1.59 g, 10.5 mmol) according to the general three-
step procedure. Purification by silica gel column chromatography
(50:1 hexane:Et2O → 25:1 hexane:Et2O) provided the product as a
1
white solid (609 mg, 24% yield). mp = 90−93 °C; H NMR (500
1
MHz, CDCl3) δ 10.49 (d, J = 0.8 Hz, 1H), 7.84 (dd, J1 = 7.7 Hz, J2
=1.9 Hz, 1H), 7.50 (ddd, J1 = 8.2 Hz, J2 = 7.3 Hz, J3 = 1.9 Hz, 1H),
7.18−7.12 (m, 2H), 2.23−2.18 (m, 3H), 1.96−1.91 (m, 3H), 1.69−
1.58 (m, 6H); 13C NMR (125 MHz, CDCl3) δ 191.2, 158.2, 134.9,
131.2, 127.9, 125.1, 123.6, 80.6, 43.0, 36.1, 31.1; HRMS (FAB+) m/z
Calcd for C17H19O2 [(M + H) − H2]+ 255.1385, found 255.1376.
pale-yellow solid (2.67 g, 83% yield). mp = 118−120 °C; H NMR
(500 MHz, CDCl3) δ 10.58 (s, 1H), 8.07 (d, J = 2.3 Hz, 1H), 7.69
(dd, J1 = 8.9 Hz, J2 = 2.3 Hz, 1H), 7.06 (d, J = 8.8 Hz, 1H), 4.64 (t, J =
3.5 Hz, 1H), 2.23−2.18 (m, 2H), 2.08 (d, J = 12.3 Hz, 2H), 1.96−1.84
(m, 4H), 1.82−1.73 (m, 4H), 1.60 (m, 2H); 13C NMR (125 MHz,
CDCl3) δ 188.5, 162.4, 132.2 (q, JC−F = 3.5 Hz), 126.1 (q, JC−F = 3.9
F
J. Org. Chem. XXXX, XXX, XXX−XXX