The Journal of Organic Chemistry
Article
1
ethyl acetate, 8:2) the title compound as a colorless solid (208.6 mg,
4.08 (t, 2H, J = 9.7 Hz). 13C{ H} NMR (CDCl , 100 MHz): δ 162.7,
3
1
9
7%). Mp 104−106 °C. H NMR (CDCl , 400 MHz): δ 8.09 (d, 2H,
152.0, 149.4, 135.5, 123.9, 123.2, 67.8, 55.0.
3
1
4
J = 8.2 Hz), 7.70 (d, 2H, J = 8.2 Hz), 4.50 (t, 2H, J = 9.4 Hz), 4.12 (t,
1,3-Bis(4,5-dihydrooxazol-2-yl)benzene (3k). The general
procedure yielded after flash chromatography (SiO , CH Cl , ethyl
acetate, 1:1) the title compound as a white solid (198.8 mg, 92%). Mp
1
2
H, J = 9.4 Hz). 13C{ H} NMR (CDCl , 100 MHz): δ 163.4, 132.8 (q,
2
2
2
3
JC−F = 33.2 Hz), 131.1, 128.5, 125.3 (q, J
= 3.6 Hz), 123.8 (q, JC−F
C−F
19
1
1
=
272.4 Hz), 67.9, 55.1. F{ H} NMR (CDCl , 376 MHz): δ −62.19.
137−139 °C. H NMR (CDCl , 400 MHz): δ 8.49−8.48 (m, 1H),
3
3
+
HRMS (ESI) m/z: [M + H] Calcd for C H F NO 216.0631; Found
8.07 (dd, 2H, J = 7.8 Hz, 1.7 Hz), 8.07 (t, 1H, J = 7.8 Hz), 4.44 (t, 4H,
10
8 3
J = 9.4 Hz), 4.07 (t, 4H, J = 9.4 Hz). 13C{ H} NMR (CDCl
1
, 100
2
16.0632.
-(4-Chlorophenyl)-4,5-dihydrooxazole (3c). The general
3
1
4
2
MHz): δ 164.1, 130.9, 128.5, 128.2, 128.0, 67.8, 55.1.
1
4
procedure yielded after flash chromatography (SiO , hexane, ethyl
1,4-Bis(4,5-dihydrooxazol-2-yl)benzene (3l). The general
procedure yielded after flash chromatography (SiO , CH Cl , ethyl
acetate, 1:1) the title compound as a white solid (156.3 mg, 72%). Mp
238−240 °C. H NMR (CDCl , 400 MHz): δ 7.99 (s, 4H), 4.45 (t,
4H, J = 9.6 Hz), 4.08 (t, 4H, J = 9.6 Hz). C{ H} NMR (CDCl
MHz): δ 164.2, 130.3, 128.2, 67.8, 55.1.
General Procedure for the Synthesis of 2-Substituted
Oxazolines with Substituted Aminoalcohols. In a glovebox, a
vial was charged with [Cu(Cl)(IPr)] (0.03 mmol), NaOAc (0.15
mmol), the nitrile (1 mmol), and aminoalcohol (3 mmol). The
reaction was stirred at 100 °C for 16 h under solvent-free conditions.
The conversion was determined by H NMR. The crude mixture was
purified by column chromatography to give the desired compound.
2
acetate, 2:8) the title compound as a colorless solid (157.5 mg, 87%).
2
2
2
1
Mp 77−79 °C. H NMR (CDCl , 400 MHz): δ 7.90−7.86 (m, 2H),
3
1
7
.40−7.37 (m, 2H), 4.44 (t, 2H, J = 9.4 Hz), 4.06 (t, 2H, J = 9.4 Hz).
C{ H} NMR (CDCl , 100 MHz): δ 163.9, 137.6, 129.6, 128.8,
3
1
3
1
13
1
, 100
3
3
1
26.4, 67.9, 55.1.
1
4
2
-p-Tolyl-4,5-dihydrooxazole (3d). The general procedure
yielded after flash chromatography (SiO , hexane, ethyl acetate, 3:7)
2
the title compound as a colorless solid (109.5 mg, 68%). Mp 69−71
1
°
(
C. H NMR (CDCl , 400 MHz): δ 7.86−7.83 (m, 2H), 7.24−7.21
3
13
1
m, 2H), 4.42 (t, 2H, J = 9.4 Hz), 4.05 (t, 2H, J = 9.4 Hz). C{ H}
1
NMR (CDCl , 100 MHz): δ 164.7, 141.6, 129.0, 128.1, 125.5, 67.5,
3
5
4.9, 21.6.
-(4-Methoxyphenyl)-4,5-dihydrooxazole (3e). The general
6
c
6
a
5-Methyl-2-phenyl-4,5-dihydrooxazole (3m). The general
procedure yielded after flash chromatography (SiO , CH Cl , ethyl
2
2
2
2
procedure yielded after flash chromatography (SiO , hexane, ethyl
2
1
acetate, 8:2) the title compound as a colorless oil (145 mg, 90%). H
NMR (CDCl , 400 MHz): δ 7.96 (d, 2H, J = 7.4 Hz), 7.51−7.47 (m,
H), 7.42 (t, 2H, J = 7.4 Hz), 4.90−4.83 (m, 1H), 4.19−4.14 (m, 1H),
3.63 (q, 1H, J = 6.2 Hz), 1.45 (d, 3H, J = 6.2 Hz). C{ H} NMR
CDCl , 100 MHz): δ 163.9, 131.2, 128.3, 128.1, 76.3, 61.6, 21.2. One
Cq missing.
-Ethyl-2-phenyl-4,5-dihydrooxazole (3n).
procedure yielded after flash chromatography (SiO , CH Cl , ethyl
acetate, 1:9) the title compound as a colorless solid (81.5 mg, 46%).
1
3
Mp 60−62 °C. H NMR (CDCl , 400 MHz): δ 7.89−7.85 (m, 2H),
3
1
6
3
1
.91−6.87 (m, 2H), 4.37 (t, 2H, J = 9.4 Hz), 4.00 (t, 2H, J = 9.4 Hz),
13
1
.81 (s, 3H). 1 C{ H} NMR (CDCl , 100 MHz): δ 164.4, 162.0,
3
1
3
(
3
29.9, 120.3, 113.7, 67.5, 55.3, 54.9.
2
-(3-Trifluoromethylphenyl)-4,5-dihydrooxazole (3f). The
23
4
The general
general procedure yielded after flash chromatography (SiO , CH Cl ,
2
2
2
2
2
2
ethyl acetate, 8:2) the title compound as a colorless oil (204.3 mg,
1
1
acetate, 8:2) the title compound as a colorless oil (155.8 mg, 89%). H
9
5%). H NMR (CDCl , 400 MHz): δ 8.25 (s, 1H), 8.15 (d, 1H, J =
3
NMR (CDCl , 400 MHz): δ 7.99−7.96 (m, 2H), 7.51−7.47 (m, 1H),
3
7
.7 Hz), 7.75 (d, 1H, J = 7.7 Hz), 7.57 (t, 1H, J = 7.7 Hz), 4.50 (t, 2H,
7
1
=
.45−7.40 (m, 2H), 4.52−4.48 (m, 1H), 4.31−4.23 (m, 1H), 4.08 (t,
13
1
J = 9.5 Hz), 4.12 (t, 2H, J = 9.5 Hz). C{ H} NMR (CDCl , 100
3
H, J = 7.9 Hz), 1.85−1.75 (m, 1H), 1.69−1.58 (m, 1H), 1.02 (t, 3H, J
MHz): δ 163.4, 131.9, 130.9 (q, JC−F = 32.9 Hz), 128.9, 128.6, 127.7
13
1
7.5 Hz). C{ H} NMR (CDCl , 100 MHz): δ 163.4, 131.2, 127.9,
3
(
q, JC−F = 3.4 Hz), 125.1 (q, J
= 3.7 Hz), 123.8 (q, JC−F = 272.4
C−F
7
2.1, 68.0, 28.6, 10.0.
-Methyl-2-(pyridin-4-yl)-4,5-dihydrooxazole (3o). The gen-
eral procedure yielded after flash chromatography (SiO , ethyl acetate)
19
1
Hz), 67.9, 55.0. F{ H} NMR (CDCl , 376 MHz): δ −62.83. HRMS
(
3
5
+
ESI) m/z: [M + H] Calcd for C H F NO 216.0631; Found
10 8 3
2
2
16.0632.
-(3-Bromophenyl)-4,5-dihydrooxazole (3g). The general
1
the title compound as a colorless oil (150.7 mg, 93%). H NMR
5
e
2
(
(
6
1
CDCl , 400 MHz): δ 8.74 (s, 2H), 7.79−7.78 (m, 2H), 4.94−4.85
3
procedure yielded after flash chromatography (SiO , hexane, ethyl
2
m, 1H), 4.21−4.15 (m, 1H), 3.65 (q, 1H, J = 6.2 Hz), 1.44 (d, 3H, J =
1
acetate, 1:1) the title compound as a colorless oil (184.5 mg, 82%). H
13
1
.2 Hz). C{ H} NMR (CDCl , 100 MHz): δ 162.2, 150.2, 135.3,
3
NMR (CDCl , 400 MHz): δ 8.10 (t, 1H, J = 1.8 Hz), 7.87 (dt, 1H, J =
+
3
22.0, 76.9, 61.7, 21.1. HRMS (ESI) m/z: [M + H] Calcd for
C H O N 163.0866; Found 163.0862.
-Ethyl-2-(pyridin-4-yl)-4,5-dihydrooxazole (3p). The general
procedure yielded after flash chromatography (SiO , ethyl acetate) the
8
.0 Hz, J = 1.3), 7.59 (dq, 1H, J = 8.0 Hz, J = 1.3), 7.27 (t, 1H, J = 8.0
13
1
9
11
1
2
Hz), 4.43 (t, 2H, J = 9.6 Hz), 4.06 (t, 2H, J = 9.6 Hz). C{ H} NMR
CDCl , 100 MHz): δ 163.4, 134.3, 131.2, 130.0, 129.8, 126.8, 122.4,
4
(
3
2
6
7.9, 55.0.
-(3,5-Difluorophenyl)-4,5-dihydrooxazole (3h). The general
1
title compound as a colorless oil (165.5 mg, 94%). H NMR (CDCl ,
3
2
4
4
1
1
00 MHz): δ 8.73 (s, 2H), 7.79 (s, 2H), 4.54−4.48 (m, 1H), 4.32−
procedure yielded after flash chromatography (SiO , hexane, ethyl
2
.23 (m, 1H), 4.11−4.06 (m, 1H), 1.82−1.72 (m, 1H), 1.68−1.57 (m,
acetate, 6:4) the title compound as a colorless solid (170.2 mg, 93%).
13
1
H), 1.02−0.98 (m, 3H). C{ H} NMR (CDCl , 100 MHz): δ 161.8,
1
3
Mp 74−76 °C. H NMR (CDCl , 400 MHz): δ 7.50−7.44 (m, 2H),
3
50.2, 135.2, 122.1, 72.5, 68.2, 28.5, 10.0. HRMS (ESI) m/z: [M +
6
.92 (tt, 1H, J = 8.8 Hz, 2.4 Hz), 4.45 (t, 2H, J = 9.4 Hz), 4.08 (t, 2H, J
+
H] Calcd for C H O N 177.1022; Found 177.1020.
9.4 Hz). 1 C{ H} NMR (CDCl , 100 MHz): δ 162.7, 162.6 (dd,
3
1
10 13
1
2
=
3
General Procedure for the Synthesis of 2-Substituted
Oxazolines - 5 mmol Scale. In the glovebox, a flame-dried Schlenk
was charged with [Cu(Cl)(IPr)] (0.1 mmol), NaOAc (0.5 mmol), the
nitrile (5 mmol), and ethanolamine (10 mmol). The reaction was
stirred at 100 °C for 16 h under solvent-free conditions. The
conversion was determined by GC analysis or by H NMR. The crude
mixture was purified by column chromatography to give the desired
JC−F = 235.7 Hz, JC−F = 12.5 Hz), 130.9 (t, JC−F = 10.4 Hz), 111.3 (dd,
J
= 19.6 Hz, JC−F = 7.8 Hz), 106.6 (t, JC−F = 25.5 Hz), 68.0, 55.0.
C−F
1
9
1
F{ H} NMR (CDCl , 376 MHz): δ −109.05. HRMS (ESI) m/z: [M
3
+
+
H] Calcd for C H F NO 184.0568; Found 184.0565.
9
8 2
1
4
1
2
-(Pyridin-4-yl)-4,5-dihydrooxazole (3i). The general proce-
dure yielded after flash chromatography (SiO , ethyl acetate) the title
2
1
compound as a white solid (122.9 mg, 83%). Mp 109−111 °C. H
compound.
NMR (CDCl , 400 MHz): δ 8.72 (s, 2H), 7.78 (s, 2H), 4.47 (t, 2H, J
2-(4-Trifluoromethylphenyl)-4,5-dihydrooxazole (3b). The
general procedure yielded after flash chromatography (SiO , CH Cl ,
3
13
1
=
9.7 Hz), 4.10 (t, 2H, J = 9.7 Hz). C{ H} NMR (CDCl , 100
3
2
2
2
MHz): δ 163.0, 150.3, 135.0, 122.0, 68.0, 55.1.
ethyl acetate, 8:2) the title compound as a colorless solid (990 mg,
1
4
1
2-(Pyridin-3-yl)-4,5-dihydrooxazole (3j). The general proce-
92%). Mp 104−106 °C. H NMR (CDCl , 400 MHz): δ 8.09 (d, 2H,
3
dure yielded after flash chromatography (SiO , ethyl acetate) the title
J = 8.2 Hz), 7.70 (d, 2H, J = 8.2 Hz), 4.50 (t, 2H, J = 9.4 Hz), 4.12 (t,
2
1
13
1
compound as a white solid (115.5 mg, 78%). Mp 68−70 °C. H NMR
2H, J = 9.4 Hz). C{ H} NMR (CDCl , 100 MHz): δ 163.4, 132.8 (q,
3
(
CDCl , 400 MHz): δ 9.15 (s, 2H), 8.71−8.69 (m, 1H), 8.21 (dt, 1H,
JC−F = 33.2 Hz), 131.1, 128.5, 125.3 (q, J
= 272.4 Hz), 67.9, 55.1. F{ H} NMR (CDCl , 376 MHz): δ −62.19.
= 3.6 Hz), 123.8 (q, JC−F
C−F
3
19
1
J = 8.0 Hz, J = 1.9 Hz), 7.36−7.34 (m, 1H), 4.46 (t, 2H, J = 9.7 Hz),
3
D
J. Org. Chem. XXXX, XXX, XXX−XXX