Job/Unit: O50332
/KAP1
Date: 23-04-15 12:31:27
Pages: 12
Synthesis of Epoxides from Aryl Aldehydes
bromo-5,6-dimethoxybenzo[c]isoxazole (4h, 0.37 g, 82%) as a col-
yl)methylphosphonate (6g, 0.77 g, 81%) as a colorless solid; m.p.
108–110 °C. H NMR (300 MHz, CDCl3): δ = 8.07–8.04 (m, 1 H,
ArH), 7.90–7.77 (m, 3 H, ArH), 7.50–7.45 (m, 3 H, ArH), 5.85 (d,
1
1
orless solid; m.p. 84–86 °C. H NMR (300 MHz, CDCl3): δ = 9.06
(s, 1 H, ArH), 3.92 (s, 3 H, -OCH3), 3.83 (s, 3 H, -OCH3) ppm. 13
C
NMR (75.4 MHz, CDCl3): δ = 157.0, 155.6, 153.5, 149.9, 118.2, J = 9.6 Hz, 1 H, CH), 4.95 (s, 1 H, OH), 4.04–3.73 (m, 4 H,
102.9, 99.9, 61.4 ppm. DEPT-135 (75.4 MHz, CDCl3): δ = 157.0, -OCH2), 1.14 (t, J = 7.05 Hz, 3 H, CH3), 1.02 (t, J = 7.05 Hz, 3
61.4 ppm. HRMS (EI): calcd. for C9H7Br2NO3 [M]+ 334.8793; H, CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 133.5, 133.0 (d,
found 334.8793.
J = 1.43 Hz), 130.8 (d, J = 6.0 Hz), 128.5, 128.4, 125.8, 125.5,
125.4, 125.2 (d, J = 3.3 Hz), 123.7, 67.1 (d, J = 161.3 Hz), 63.2 (q,
J = 7.54 Hz), 16.2 (q, J = 5.65 Hz) ppm. DEPT-135 (75.4 MHz,
CDCl3): δ = 128.5, 128.4, 125.8, 125.6, 125.5, 125.4, 125.3, 125.2,
123.7, 67.1 (d, J = 161.3 Hz), 63.2 (q, J = 7.54 Hz), 16.2 (q, J =
5.65 Hz) ppm. HRMS (EI): calcd. for C15H19O4P [M]+ 294.1021;
found 294.1020.
Methyl 4-[(Diethoxyphosphoryl)(hydroxy)methyl]benzoate (6c): The
reaction of methyl 4-formylbenzoate (5c, 0.5 g, 3.04 mmol) with
triethyl phosphite (1.5 g, 9.14 mmol) in the presence of ZnBr2
(0.07 g, 0.30 mmol) at room temperature for 20 min followed by
workup using general procedure B afforded methyl 4-[(diethoxy-
phosphoryl)(hydroxy)methyl]benzoate (6c, 0.72 g, 79%) as a color-
less solid; m.p. 106–108 °C. 1H NMR (300 MHz, CDCl3): δ = 8.01
(d, J = 7.8 Hz, 2 H, ArH), 7.56 (d, J = 7.8 Hz, 2 H, ArH), 5.10 (d,
J = 12.6 Hz, 1 H, CH), 4.04 (q, J = 6.7 Hz, 4 H, -OCH2), 3.91 (s,
3 H, OCH3), 1.27–1.20 (m, 6 H, CH3) ppm. 13C NMR (75.4 MHz,
CDCl3): δ = 166.8, 142.1 (d, J = 3.7 Hz), 129.4, 129.2, 126.8 (d, J
= 5.2 Hz), 70.3 (d, J = 149.3 Hz), 63.4 (d, J = 7.5 Hz), 63.0 (d, J
= 7.5 Hz), 51.9, 51.9, 16.2 (d, J = 6.0 Hz) ppm. DEPT-135
(75.4 MHz, CDCl3): δ = 129.5, 126.8 (d, J = 5.2 Hz), 70.27 (d, J =
159.0 Hz), 63.48 (d, J = 7.5 Hz), 63.0 (d, J = 7.5 Hz), 51.9, 16.2 (d,
Diethyl (3a1,8-Dihydropyren-1-yl)(hydroxy)methylphosphonate (6h):
The reaction of pyrene-1-carbaldehyde (5h, 0.5 g, 2.17 mmol) with
triethyl phosphite (1.1 g, 6.51 mmol) in the presence of ZnBr2
(0.05 g, 0.22 mmol) at room temperature for 30 min followed by
workup using general procedure B afforded diethyl hydroxy(pyren-
1-yl)methylphosphonate 6h (0.68 g, 83%) as a colorless solid; m.p.
168–170 °C. 1H NMR (300 MHz, CDCl3): δ = 8.39 (dd, J1
=
8.1 Hz, J2 = 8.1 Hz, 1 H, ArH), 8.24 (d, J = 9.3 Hz, 1 H, ArH),
8.18–8.12 (m, 3 H, ArH), 8.05–7.95 (m, 3 H, ArH), 6.13 (d, J =
11.4 Hz, 1 H, CH), 4.73 (s, 1 H, -OH), 4.06–3.78 (m, 4 H, -OCH2),
1.15 (t, J = 7.05 Hz, 3 H, CH3), 1.03 (t, J = 7.05 Hz, 3 H,
CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 131.3, 131.1 (d, J
= 3.0 Hz), 130.6, 130.3 (d, J = 0.45 Hz), 128.3 (d, J = 6.9 Hz),
128.5, 127.5, 127.5, 127.4, 125.9, 125.3, 125.2, 125.1, 124.9 (d, J =
3.1 Hz), 124.6, 123.0, 67.7 (d, J = 161.2 Hz), 63.3 (q, J = 7.54 Hz),
16.3 (t, J = 5.65 Hz) ppm. DEPT-135 (75.4 MHz, CDCl3): δ =
127.5 (d, J = 6.9 Hz), 125.9, 125.3, 125.2, 125.1, 124.9 (d, J =
3.1 Hz), 124.6, 123.0, 67.7 (d, J = 161.2 Hz), 63.3 (q, J = 7.54 Hz),
16.3 (t, J = 5.65 Hz) ppm. HRMS (EI): calcd. for C21H21O4P
[M]+ 368.1177; found 368.1170.
J
=
6.0 Hz) ppm. HRMS (EI): calcd. for C13H19O6P [M]+
302.0919; found 302.0910.
Diethyl Hydroxy[4-(trifluoromethyl)phenyl]methylphosphonate (6d):
The reaction of 4-(trifluoromethyl)benzaldehyde (5d, 0.5 g,
2.87 mmol) with triethyl phosphite (1.4 g, 8.61 mmol) in the pres-
ence of ZnBr2 (0.07 g, 0.28 mmol) at room temperature for 20 min
followed by workup using general procedure B afforded diethyl hy-
droxy[4-(trifluoromethyl)phenyl]methylphosphonate (6d, 0.60 g,
68%) as a colorless solid; m.p. 150–152 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.59 (s, 4 H, ArH), 5.11 (d, J = 12 Hz, 1 H, CH), 4.97
(s, 1 H, OH), 4.06–4.05 (m, 4 H, -OCH2), 1.27–1.20 (m, 6 H,
-CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 141.0, 129.9 (d, J
= 35.4 Hz), 127.3 (d, J = 5.2 Hz), 125.9, 124.9 (d, J = 3.0 Hz),
122.2, 70.0 (d, J = 159.8 Hz), 63.5 (q, J = 7.1 Hz), 16.3 (d, J =
4.5 Hz) ppm. DEPT-135 (75.4 MHz, CDCl3): δ = 127.3 (d, J =
5.2 Hz), 125.0, 124.9 (d, J = 3.0 Hz), 70.0 (d, J = 159.8 Hz), 63.5
(q, J = 7.1 Hz), 16.3 (d, J = 4.5 Hz) ppm. C12H16F3O4P (312.22):
calcd. C 46.16, H 5.17; found C 46.39, H 4.95.
Ethyl
2-[2-Methyl-1-(phenylsulfonyl)-1H-indol-3-yl]-2-oxoacetate
(12): To a solution of 2-methylindole (2 g, 15.2 mmol) in dry diethyl
ether (10 mL) was slowly added oxalyl dichloride (3.9 g,
30.53 mmol) at 0 °C, and the resulting mixture was stirred for 1 h.
Dry ethanol (10 mL) was slowly added, and the mixture was stirred
for an additional 1 h. The resulting reaction mixture was poured
over crushed ice (200 g), the resulting solid was filtered off and
dried with CaCl2 in a desiccator to give ethyl 2-(2-methyl-1H-indol-
3-yl)-2-oxoacetate (2.65 g, 80%) as a brown solid; m.p. 158–160 °C.
1H NMR (300 MHz, CDCl3): δ = 9.95 (s, 1 H, NH), 7.98 (d, J =
6.9 Hz, 1 H, ArH), 7.33 (d, J = 6.9 Hz, 1 H, ArH), 7.30–7.21 (m,
3 H, ArH), 4.41 (q, J = 6.9 Hz, 2 H, -OCH2), 2.62 (s, 3 H, CH3),
1.36 (t, J = 7.0 Hz, 3 H, CH3) ppm. 13C NMR (75.4 MHz, CDCl3):
δ = 182.3, 166.5, 148.0, 135.1, 126.7, 123.5, 123.0, 120.4, 111.5,
109.8, 62.2, 14.4, 14.0 ppm. DEPT-135 (75.4 MHz, CDCl3): δ =
123.5, 123.0, 120.4, 111.5, 62.2, 14.4, 14.0 ppm. To a solution of
Diethyl (3,6-Dimethoxy-2-nitrophenyl)(hydroxy)methylphosphonate
(6e): The reaction of 3,6-dimethoxy-2-nitrobenzaldehyde (5e,[34]
0.5 g, 2.36 mmol) with triethyl phosphite (1.2 g, 7.10 mmol) in the
presence of ZnBr2 (0.05 g, 0.23 mmol) at room temperature for
10 min followed by workup using general procedure B gave diethyl
(3,6-dimethoxy-2-nitrophenyl)(hydroxy)methylphosphonate
(6e,
0.65 g, 79%) as a colorless solid; m.p. 172–174 °C. 1H NMR
(300 MHz, CDCl3): δ = 6.99 (s, 2 H, ArH), 5.14 (d, J = 17.1 Hz, 1
H, CH), 4.40 (s, 1 H, OH), 4.45–3.97 (m, 4 H, -OCH2), 3.91 (s, 3
H, -OMe), 3.83 (s, 3 H, -OMe), 1.32 (t, J = 7.05 Hz, 3 H, CH3),
1.20 (t, J = 7.05 Hz, 3 H, CH3) ppm. 13C NMR (75.4 MHz,
CDCl3): δ = 151.6 (d, J = 3.77 Hz), 145.1, 140.9, 119.2, 113.6,
113.0, 66.4 (d, J = 161.3 Hz), 63.1 (t, J = 6.78 Hz), 56.9 (d, J =
3.77 Hz), 16.3 (q, J = 6.0 Hz) ppm. DEPT-135 (75 MHz, CDCl3):
δ = 113.6, 113.0, 66.4 (d, J = 161.3 Hz), 63.1 (t, J = 6.78 Hz), 56.9
(d, J = 3.77 Hz), 16.3 (q, J = 6.0 Hz) ppm. HRMS (EI): calcd. for
C13H20NO8P [M]+ 349.0927; found 349.0920.
crude
ethyl
2-(2-methyl-1H-indol-3-yl)-2-oxoacetate
(2 g,
8.65 mmol) in dry dichloromethane (DCM, 25 mL) were added
Et3N (1.76 g, 17.3 mmol) and 4-(N,N-dimethylamino)pyridine
(DMAP, 105 mg, 0.87), and the resulting mixture was stirred for
15 min. Benzenesulfonyl chloride (2.0 g, 11.24 mmol) in dry DCM
(10 mL) was then added, and the reaction was stirred for an ad-
ditional 6 h. The reaction mixture was then poured over 2% aque-
ous HCl (10 mL) and brine (10 mL). The organic layer was sepa-
rated and then dried with Na2SO4. Removal of solvent followed by
column chromatographic purification (10% EA in hexane) afforded
Diethyl Hydroxy(naphthalen-1-yl)methylphosphonate (6g): The reac-
tion of 1-naphthaldehyde (5g, 0.5 g, 3.20 mmol) with triethyl phos-
phite (1.6 g, 9.60 mmol) in the presence of ZnBr2 (0.07 g,
ethyl
2-[2-methyl-1-(phenylsulfonyl)-1H-indol-3-yl]-2-oxoacetate
1
(12, 2.8 g, 87%) as a light brown solid; m.p. 98–100 °C. H NMR
0.32 mmol) at room temperature for 30 min followed by workup (300 MHz, CDCl3): δ = 8.25 (d, J = 9.0 Hz, 1 H, ArH), 7.88–7.80
using general procedure B afforded diethyl hydroxy(naphthalen-1- (m, 3 H, ArH), 7.63–7.59 (m, 1 H, ArH), 7.49 (t, J = 7.5 Hz, 2 H,
Eur. J. Org. Chem. 0000, 0–0
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