The Journal of Organic Chemistry
Note
temperature. A solution of benzophenone derivative (10.989 mmol,
1.0 equiv) was then slowly added at 0 °C, and the mixture was
stirred at room temperature for 24 h. The reaction mixture was
treated with satd aq NH4Cl solution, and the aqueous phase was
extracted with EtOAc. The combined organic layer was washed with
brine and dried over Na2SO4. The solvent was evaporated, and the
residue was purified by silica gel column chromatography using 2%
ethyl acetate in petroleum ether (2/100) as an eluent to afford the
desired product.
2-(2,5-Dimethoxy-4-methylphenyl)-3-(4-methoxyphenyl)-2-
methylpropanal (3c). Compound 3c was prepared according to the
general procedure A by treating enol ether 1c (89 mg, 0.4 mmol, 1.0
equiv) and 2a (55 mg, 0.4 mmol, 1.0 equiv) in 1,2-DCE (2 mL).
Purification of the crude material by silica gel column chromatog-
raphy using 2% ethyl acetate in petroleum ether (2/100) as an
eluent furnished the compound 3c as a colorless liquid (96 mg,
1
73%). H NMR (400 MHz, CDCl3) δ = 9.59 (s, 1 H), 6.75 (s, 1
H), 6.68−6.51 (m, 4 H), 6.28 (s, 1 H), 3.73 (s, 6 H), 3.60 (s, 3 H),
3.19 (d, J = 13.7 Hz, 1 H), 3.06 (d, J = 13.7 Hz, 1 H), 2.24 (s, 3
H), 1.20 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3) δ 203.6,
157.9, 151.7, 150.4, 131.6, 129.4, 127.3, 126.9, 114.1, 112.9, 111.9,
56.3, 55.9, 55.1, 52.7, 38.9, 19.2, 16.2. IR νmax (neat): 2936, 1721,
1505, 1457, 1396, 1205, 1037, 881 cm−1. HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C20H25O4 329.1747, found 329.1754
1,4-Dimethoxy-2-(1-methoxyprop-1-en-2-yl)-5-methylbenzene
1
(1c). Colorless liquid; 2.2 g, 96%. H NMR (400 MHz, CDCl3) δ =
6.73 (s, 1 H), 6.68 (s, 2 H), 6.63 (s, 1 H), 6.22 (d, J = 1.5 Hz, 1
H), 6.02 (q, J = 1.5 Hz, 1 H), 3.79 (s, 3 H), 3.78 (s, 3 H), 3.77 (s,
3 H), 3.77 (s, 3 H), 3.68 (s, 3 H), 3.54 (s, 3 H), 2.21 (s, 6 H), 1.96
(d, J = 1.5 Hz, 3 H), 1.87 (d, J = 1.5 Hz, 3 H). 13C{1H} NMR (100
MHz, CDCl3) δ = 151.5, 151.1, 150.5, 146.1, 143.2, 133.8, 133.6,
128.5, 126.0, 125.9, 125.3, 114.9, 114.6, 113.2, 112.5, 111.6, 59.7,
59.6, 56.5, 56.3, 56.1, 56.0, 18.7, 16.3, 16.1, 14.0. IR νmax (neat):
2935, 1671, 1504, 1458, 1398, 1208, 1140, 1043, 861 cm−1. HRMS
(ESI-TOF) m/z: [M + NH4]+ calcd for C13H22 NO3 240.1594,
found 240.1586.
2-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-2-methylpropa-
nal (3d). Compound 3d was prepared according to the general
procedure A by treating enol ether 1d (83 mg, 0.4 mmol, 1.0 equiv)
and 2a (55 mg, 0.4 mmol, 1.0 equiv) in 1,2-DCE (2 mL).
Purification of the crude material by silica gel column chromatog-
raphy using 2% ethyl acetate in petroleum ether (2/100) as an
eluent furnished the compound 3d as a colorless liquid (92 mg,
1,2-Dimethoxy-4-(1-methoxyprop-1-en-2-yl)benzene (1d).22 1H
NMR (400 MHz, CDCl3) δ = 7.24 (s, 1 H), 7.03 (d, J = 8.3 Hz, 1
H), 6.79−6.71 (m, 4 H), 6.25 (s, 1 H), 5.99 (s, 1 H), 3.81 (s, 6 H),
3.79 (s, 6 H), 3.63 (s, 3 H), 3.60 (s, 3 H), 1.90 (s, 3 H), 1.82 (s, 3
H).
1
73%). H NMR (400 MHz, CDCl3) δ = 9.57 (s, 1 H), 6.85 (d, J =
8.3 Hz, 1 H), 6.74−6.71 (m, 3 H), 6.70−6.67 (m, 2 H), 6.61 (d, J
= 2.0 Hz, 1 H), 3.88 (s, 3 H), 3.81 (s, 3 H), 3.73 (s, 3 H), 3.11 (s,
2 H), 1.34 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3) δ 202.1,
158.2, 149.0, 148.4, 131.6, 131.3, 129.9, 128.9, 120.0, 113.6, 113.3,
111.2, 111.0, 55.9, 55.9, 55.1, 54.7, 41.8, 18.4. IR νmax (neat): 2934,
1597, 1511, 1456, 1255, 1028, 810 cm−1. HRMS (ESI-TOF) m/z:
[M + Na]+ calcd for C19H22O4Na 337.1410, found 337.1408
3-(4-Methoxyphenyl)-2-methyl-2-(p-tolyl)propanal (3e). Com-
pound 3e was prepared according to the general procedure A by
treating enol ether 1e (65 mg, 0.4 mmol, 1.0 equiv) and 2a (55 mg,
0.4 mmol, 1.0 equiv) in 1,2-DCE (2 mL). Purification of the crude
material by silica gel column chromatography using 2% ethyl acetate
in petroleum ether (2/100) as an eluent furnished the compound 3e
1-Methoxy-4-(1-methoxybut-1-en-2-yl)benzene (1o).23 1H NMR
(400 MHz, CDCl3) δ = 7.44−7.40 (m, 2 H), 7.21−7.18 (m, 2 H),
6.88−6.81 (m, 4 H), 6.17 (s, 1 H), 6.02 (s, 1 H), 3.78 (s, 6 H),
3.65 (s, 3 H), 3.60 (s, 3 H), 2.49 (d, J = 7.8 Hz, 2 H), 2.29 (dd, J =
1.0, 7.3 Hz, 2 H), 0.99 (dt, J = 4.9, 7.3 Hz, 6 H).
(Methoxymethylene)cycloheptane (1t).25 1H NMR (400 MHz,
CDCl3) δ = 5.78−5.76 (m, 1 H), 3.54 (s, 3 H), 2.29−2.25 (m, 2
H), 2.07−2.02 (m, 2 H), 1.59−1.47 (m, 8 H).
General Procedure A for the Synthesis of Compound 3a.
To a stirred solution of compounds 1a (1-methoxy-4-(1-methox-
yprop-1-en-2-yl)benzene (71 mg, 0.4 mmol, 1.0 equiv) and 2a (55
mg, 0.4 mmol, 1.0 equiv) in 1,2-DCE (2 mL) was added ZnBr2 (90
mg, 0.4 mmol, 1.0 equiv) at room temperature, and the mixture
stirred until complete conversion of starting material (monitored by
TLC) for 5 h. After completion of the reaction, it was diluted with
water (2 mL), and the aqueous layer was extracted with
dichloromethane (2 × 10 mL). All organic layers were dried over
Na2SO4, solvent was evaporated at reduced pressure, and the
product was isolated by using column chromatography 3% ethyl
acetate in petroleum ether (3/100) as an eluent.
1
as a colorless liquid (81 mg, 72%). H NMR (400 MHz, CDCl3) δ
= 9.58 (s, 1 H), 7.16 (d, J = 7.8 Hz, 2 H), 7.06 (d, J = 8.3 Hz, 2
H), 6.75−6.64 (m, 4 H), 3.73 (s, 3 H), 3.22−2.99 (m, 2 H), 2.34
(s, 3 H), 1.33 (s, 3 H). 13C{1H}NMR (100 MHz, CDCl3) δ 202.2,
158.2, 137.1, 136.4, 131.4, 129.5, 128.9, 127.5, 113.3, 55.1, 54.8,
41.8, 21.0, 18.3. IR νmax (neat): 2928, 1609, 1509, 1456, 1245, 1177,
1032, 819 cm−1. HRMS (ESI-TOF) m/z: [M + NH4]+ calcd for
C18H24NO2 286.1802, found 286.1801.
3-(4-Methoxyphenyl)-2-methyl-2-phenylpropanal (3f). Com-
pound 3f was prepared according to the general procedure A by
treating enol ether 1f (59 mg, 0.4 mmol, 1.0 equiv) and 2a (55 mg,
0.4 mmol, 1.0 equiv) in 1,2-DCE (2 mL). Purification of the crude
material by silica gel column chromatography using 2% ethyl acetate
in petroleum ether (2/100) as an eluent furnished the compound 3f
2,3-Bis(4-methoxyphenyl)-2-methylpropanal (3a). Colorless
1
liquid (98 mg, 86%), H NMR (400 MHz, CDCl3) δ = 9.58 (s,
1 H), 7.09 (d, J = 8.9 Hz, 2 H), 6.90 (d, J = 8.9 Hz, 2 H), 6.74−
6.67 (m, 4 H), 3.82 (s, 3 H), 3.74 (s, 3 H), 3.15−3.06 (m, 2 H),
1.33 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3) δ 202.1, 158.8,
158.1, 131.3, 131.1, 128.9, 128.7, 114.1, 113.2, 55.2, 55.1, 54.4, 41.8,
18.3. IR νmax (neat): 2935, 1606, 1508, 1457, 1246, 1176, 1037, 816
cm−1. HRMS (ESI-TOF) m/z: [M + NH4]+ calcd for C18H24NO3
302.1751, found 302.1754.
1
as a colorless liquid (74 mg, 73%). H NMR (400 MHz, CDCl3) δ
= 9.62 (s, 1 H), 7.38−7.33 (m, 2 H), 7.31−7.27 (m, 1 H), 7.19−
7.15 (m, 2 H), 6.79−6.55 (m, 4 H), 3.18−3.08 (m, 2 H), 1.36 (s, 3
H). 13C{1H} NMR (100 MHz, CDCl3) δ 202.2, 158.2, 139.4, 131.3,
128.7, 127.6, 127.4, 113.2, 55.1, 55.1, 41.8, 18.2. IR νmax (neat):
2931, 1707, 1607, 1507, 1458, 1245, 1176, 1032, 819 cm−1. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C17H19O2 255.1380, found
255.1383.
2-(4-Fluorophenyl)-3-(4-methoxyphenyl)-2-methylpropanal
(3g). Compound 3g was prepared according to the general
procedure A by treating enol ether 1g (66 mg, 0.4 mmol, 1.0
equiv) and 2a (55 mg, 0.4 mmol, 1.0 equiv) in 1,2-DCE (2 mL).
Purification of the crude material by silica gel column chromatog-
raphy using 2% ethyl acetate in petroleum ether (2/100) as an
eluent furnished the compound 3g as white solid (80 mg, 74%). Mp
= 97−98 °C. 1H NMR (400 MHz, CDCl3) δ = 9.60 (s, 1 H),
7.15−7.09 (m, 2 H), 7.08−7.01 (m, 2 H), 6.69 (s, 4 H), 3.74 (s, 3
H), 3.16−3.04 (m, 2 H), 1.36 (s, 3 H). 13C {1H} NMR (100 MHz,
CDCl3) δ 201.9, 162.03 (d, JCF = 245 Hz), 158.2, 135.1, 131.3,
129.28 (d, JCF = 8 Hz), 128.4, 115.57 (d, JCF = 21 Hz), 113.3, 55.1,
2-(2,5-Dimethoxyphenyl)-3-(4-methoxyphenyl)-2-methylpropa-
nal (3b). Compound 3b was prepared according to the general
procedure A by treating enol ether 1b (83 mg, 0.4 mmol, 1.0 equiv)
and 2a (55 mg, 0.4 mmol, 1.0 equiv) in 1,2-DCE (2 mL).
Purification of the crude material by silica gel column chromatog-
raphy using 2% ethyl acetate in petroleum ether (2/100) as an
eluent furnished the compound 3b as a colorless liquid (89 mg,
1
71%). H NMR (400 MHz, CDCl3) δ = 9.59 (s, 1 H), 6.89−6.78
(m, 2 H), 6.67−6.57 (m, 4 H), 6.43 (d, J = 2.9 Hz, 1 H), 3.74 (s, 6
H), 3.68 (s, 3 H), 3.24 (d, J = 13.6 Hz, 1 H), 3.05 (d, J = 13.5 Hz,
1 H), 1.21 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3) δ 203.3,
157.9, 153.6, 150.9, 131.5, 130.9, 129.2, 115.8, 113.0, 112.5, 111.7,
55.8 (2C), 55.1, 52.8, 38.8, 19.2. IR νmax (neat): 2940, 1695, 1507,
1230, 1177, 1039, 811 cm−1. HRMS (ESI-TOF) m/z: [M + H]+
calcd for C19H23O4 315.1591, found 315.1589.
F
J. Org. Chem. XXXX, XXX, XXX−XXX