FULL PAPERS
Synthesis of 3-Arylated 3,4-Dihydrocoumarins
3
4
3
4
À1
1
J=7.5 Hz, J=0.9 Hz, 1H, 6-H), 7.02 (dd, J=8.1 Hz, J=
1140, 1023, 918, 867, 756 cm ; H NMR (600 MHz, MeOH-
3 4
4
0
.9 Hz, 1H, 8-H), 6.70 (d, J=2.2 Hz, 1H, 2’-H), 6.62 (d,
d ): d=7.27 (td, J=8.1 Hz, J=1.7 Hz, 1H, 7-H), 7.21 (dd,
4
4
3
4
3
4
J=2.2 Hz, 1H, 6’-H), 6.23 (s, 1H, 3’-OH), 5.54 (s, 1H, 4’-
J=7.4 Hz, J=1.7 Hz, 1H, 5-H), 7.09 (td, J=7.4 Hz, J=
3
2
3
4
OH), 4.11 (q, J=7.1 Hz, 2H, OCH CH ), 3.69 (d, J=
1
3
1.2 Hz, 1H, 6-H), 7.05 (dd, J=8.1 Hz, J=1.2 Hz, 1H, 8-
H), 6.60 (s, 2H, 3’-H, 6’-H), 4.12 (m, 2H, OCH CH ), 3.72
2
3
2
5.7 Hz, 1H, 4-H), 3.55 (d, J=15.7 Hz, 1H, 4-H), 2.18 (s,
H, 5’-CH ), 1.05 (t, J=7.1 Hz, 3H, OCH CH ); C NMR
2
3
3
13
2
2
(d, J=15.8 Hz, 1H, 4-H), 3.64 (d, J=15.8 Hz, 1H, 4-H),
3
2
3
(
151 MHz, CDCl ): d=169.43 (CO Et), 167.63 (C-2), 150.92
3.32 (m, 2H, 4’-OH, 5’-OH), 2.13 (s, 3H, 2’-CH ), 1.07 (t,
3
2
3
3
13
(
C-8a), 143.16 (C-3’), 142.71 (C-4’), 128.68 (C-8), 128.33 (C-
J=7.1 Hz, 3H, OCH CH ); C NMR (151 MHz, MeOH-
2 3
7
1
), 125.36 (C-4a), 124.85 (C-6), 124.51 (C-1’), 121.54 (C-5’),
21.29 (C-6’), 116.40 (C-5), 112.55 (C-2’), 62.67
d ): d=171.48 (CO Et), 168.45 (C-2), 152.76 (C-8a), 145.78
4 2
(C-5’), 143.78 (C-4ꢂ), 129.67 (C-7), 129.45 (C-5), 129.39 (C-
1’), 125.83 (C-6), 125.79 (C-2’), 123.04 (C-4a), 120.33 (C-6’),
116.90 (C-8), 116.19 (C-3’), 63.38 (CO CH CH ), 59.76 (C-
(CO CH CH ), 58.00 (C-3), 33.44 (C-4), 15.73 (C-5’CH ),
2
2
3
3
1
3.70 (CO CH CH ); HR-MS (ESI): m/z=341.1030
2 2 3
+
2
2
3
À
[MÀH] , calculated for C H O : 341.1030.
3), 35.08 (C-4), 20.46 (C-2’CH ), 14.04 (CO CH CH ); HR-
3 2 2 3
+
1
9
17
6
Ethyl 3-(3,4-dihydroxy-5-fluorophenyl)-2-oxochroman-3-
MS (ESI): m/z=341.1030 [MÀH] , calculated for
À
carboxylate (16d) and ethyl 3-(2-fluoro-3,4-dihydroxyphen-
C H O : 341.1030.
1
9
17
6
yl)-2-oxochroman-3-carboxylate (17d): Reaction of 12a
Ethyl 3-(2-chloro-4,5-dihydroxyphenyl)-2-oxochroman-3-
carboxylate (16f): Reaction of 12a (55 mg, 0.25 mmol) and
15f (40 mg, 0.30 mmol) according to the general procedure
after 20 h gave 16f as a yellow solid; yield: 57.0 mg (63%);
(
55 mg, 0.25 mmol) and 15d (40 mg, 0.30 mmol) according to
the general procedure after 19 h gave 16d and 17d as
a 78:22 mixture of regioisomers; yield: 55.4 mg (64%); Rf
0
.15 (petroleum ether/ethyl acetate 70/30); HR-MS (ESI):
mp 48–528C; R =0.18 (petroleum ether/ethyl acetate 70/
f
+
À
:
6
m/z=345.0780 [MÀH] , calculated for C H FO
30); IR (ATR): n=3385, 2917, 1765, 1735, 1489, 1459, 1231,
1
8
14
À1
1
3
45.0780.
Major isomer 16d: pale yellow solid; mp 43–478C; IR
ATR): n=3386, 2961, 2526, 1753, 1721, 1524, 1236, 1138,
1142, 1019, 918, 863, 756 cm ; H NMR (600 MHz, MeOH-
3 4
d ): d=7.27 (td, J=7.8 Hz, J=1.6 Hz, 1H, 7-H), 7.17 (dd,
4
3
4
(
J=7.4 Hz, J=1.5 Hz, 1H, 5-H), 7.08 (m, 2H, 6-H, 8-H),
6.78 (s, 1H, 3’-H), 6.58 (s, 1H, 6’-H), 4.21 (m, 2H,
À1
4
1
1
017, 919, 755, 661 cm ; H NMR (600 MHz, MeOH-d ):
4
3
3
2
2
d=7.31 (dd, J=7.5 Hz, J=1.5 Hz, 1H, 5-H), 7.28 (td, J=
7
1
H), 6.62 (d, JH,H =2.3 Hz, 1H, 2ꢂ-H), 6.61 (dd, J6’-H,F)
1
OCH CH ), 3.69 (d, J=15.8 Hz, 1H, 4-H), 3.66 (d, J=
OCH CH ), 3.99 (d, J=16.0 Hz, 1H, 4-H), 3.69 (d, J=
2 3
4
3
4
3
.8 Hz, J=1.6 Hz, 1H, 7-H), 7.13 (td, J=7.5 Hz, J=
16.0 Hz, 1H, 4-H), 1.16 (t, J=7.1 Hz, 3H, OCH CH );
2 3
C NMR (151 MHz, MeOH-d ): d=170.40 (CO Et), 167.57
3
4
13
.2 Hz, 1H, 6-H), 7.02 (dd, J=8.2 Hz, J=1.2 Hz, 1H, 8-
4
2
4
3
=
(C-2), 152.45 (C-8a), 147.12 (C-4’), 145.35 (C-5’), 129.66 (C-
7), 129.53 (C-5), 126.05 (C-6), 124.71 (C-2’), 123.89 (C-1’),
122.90 (C-4a), 118.95 (C-6’), 117.20 (C-3’), 116.99 (C-8),
63.63 (CO CH CH ), 60.34 (C-3), 34.06 (C-4), 14.10
4
3
5.1 Hz, J =2.3 Hz, 1H, 6ꢂ-H), 4.10 (q, J=7.1 Hz, 2H,
H,H
2 2
2
3
3
1
5.8 Hz, 1H, 4-H), 1.06 (t, J=7.1 Hz, 3H, OCH CH );
2 3
2
2
3
13
+
C NMR (151 MHz, MeOH-d ): d=170.49 (CO Et), 168.10
(CO CH CH ); HR-MS (ESI): m/z=361.0484 [MÀH] , cal-
4
2
2
2
3
1
À
(
C-2), 153.11 (d, J=238 Hz, C-5’), 152.52 (C-8a), 148.46 (d,
culated for C H ClO : 361.0484.
18 14 6
3
2
J=5.8 Hz, C-3’), 134.56 (d, J=15.0 Hz, C-4’), 129.75 (C-7),
Ethyl 3-(3,4-dihydroxy-5-methoxyphenyl)-6-methyl-2-oxo-
chroman-3-carboxylate (16g): Reaction of 12b (58 mg,
0.25 mmol) and 15b (42 mg, 0.30 mmol) according to the
general procedure after 24 h gave 16g as a brown solid;
3
126.60 (d, J=8.4 Hz, C-1’), 125.89 (C-5), 123.30 (C-6),
4
2
1
2
3
17.14 (C-4a), 112.01 (d, J=1.7 Hz, C-2’), 107.45 (d, J=
1.7 Hz, C-6’), 102.60 (C-8), 63.50 (CO CH CH ), 59.29 (C-
2
2
3
), 34.13 (C-4), 14.08 (CO CH CH ).
yield: 86.5 mg (94%); mp 50–578C; R =0.18 (petroleum
2
2
3
f
Minor isomer 17d: white solid; mp 53–578C; IR (ATR):
n=3386, 2928, 2531, 1759, 1728, 1460, 1231, 1140, 1022, 919,
ether/ethyl acetate 70/30); IR (ATR): n=3438, 2937, 1754,
À1
1728, 1615, 1521, 1463, 1258, 1201, 1138, 1085, 815, 692 cm ;
À1
1
1
4
7
56, 665 cm ; H NMR (600 MHz, MeOH-d ): d=7.29 (td,
H NMR (600 MHz, MeOH-d ): d=7.12 (d, J=2.0 Hz, 1H,
4
3
4
3
4
4
3
4
J=7.9 Hz, J=1.6 Hz, 1H, 7-H), 7.24 (dd, J=7.6 Hz, J=
5-H), 7.07 (dd, J=8.3 Hz, J=2.0 Hz, 1H, 7-H), 6.89 (d,
3
4
3
4
4
1
7
.6 Hz, 1H, 5-H), 7.11 (td, J=7.5 Hz, J=1.2 Hz, 1H, 6-H),
.06 (dd, J=8.2 Hz, J=1.2 Hz, 1H, 8-H), 6.52 (dd, J
J=8.3 Hz, 1H, 8-H), 6.47 (d, J=2.2 Hz, 1H, 2ꢂ-H), 6.46 (d,
J=2.2 Hz, 1H, 6ꢂ-H), 4.12 (m, 2H, OCH CH ), 3.80 (s, 3H,
3
4
3
=
H,H
2
3
5
4
3
8
.5 Hz, J5
=1.4 Hz, 1H, 5’-H), 6.48 (dd, J6’-H,F =7.9 Hz,
5’-OCH ), 3.65 (s, 2H, 4-H), 2.30 (s, 3H, 6-CH ), 1.09 (t, J=
3 3
13
’-H,F
3
JH,H =8.5 Hz, 1H, 6’-H), 4.13 (m, 2H, OCH CH ), 3.74 (d,
J=15.7 Hz, 1H, 4-H), 3.61 (d, J=15.7 Hz, 1H, 4-H), 1.07
7.1 Hz, 3H, OCH CH ); C NMR (151 MHz, MeOH-d ):
2 3 4
2
3
2
2
d=170.89 (CO Et), 168.73 (C-2), 150.46 (C-5’), 149.42 (C-
2
1
3
(m, 3H, OCH CH ); C NMR (151 MHz, MeOH-d ): d=
8a), 146.45 (C-3’), 135.72 (C-6), 135.40 (C-4’), 130.03 (C-5),
130.02 (C-7), 126.46 (C-1’), 123.19 (C-4a), 116.82 (C-8),
109.83 (C-2’), 104.43 (C-6’), 63.33 (CO CH CH ), 59.69 (C-
2
3
4
1
1
1
70.43 (CO Et), 167.52 (C-2), 166.26 (d, J=244 Hz, C-2’),
52.80 (C-8a), 149.23 ( J=5.1 Hz, C-4’), 143.44 ( J=13.8 Hz,
2
3
2
2
2
3
4
C-3’), 129.77 (C-8a), 129.78 (C-5), 129.59 (C-7), 125.89 ( J=
3), 56.73 (C-5’OCH ), 34.29 (C-4), 20.73 (C-6 CH ), 14.15
3 3
+
3
4
5
.4 Hz, C-6’), 125.92 (C-6), 122.91 (C-4a), 118.15 ( J=
(CO CH CH ); HR-MS (ESI): m/z=371.1136 [MÀH] , cal-
2
2
3
5
À
.1 Hz, C-6’), 117.11 (C-8), 111.18 ( J=1.8 Hz, C-5’), 110.59
culated for C H O : 371.1136.
20 19 7
2
(
(
J=21.5 Hz, C-1’), 63.50 (CO CH CH ), 57.75 (C-3), 34.63
Ethyl
3-(3,4-dihydroxy-5-methoxyphenyl)-6-methoxy-2-
2
2
3
C-4), 14.07 (CO CH CH ).
oxochroman-3-carboxylate (16h): Reaction of 12c (62 mg,
0.25 mmol) and 15b (42 mg, 0.30 mmol) according to the
general procedure after 46 h gave 16h as a pale brown solid;
yield: 81.0 mg (84%); mp 48–538C; Rf 0.08 (petroleum
ether/ethyl acetate 70/30); IR (ATR): n=3430, 2939, 2843,
1754, 1728, 1614, 1521, 1494, 1198, 1139, 1086, 1019, 811,
2
2
3
Ethyl 3-(2-methyl-4,5-dihydroxyphenyl)-2-oxochroman-3-
carboxylate (16e): Reaction of 12a (55 mg, 0.25 mmol) and
5e (37 mg, 0.30 mmol) according to the general procedure
1
after 20 h gave 16e as a yellow solid; yield: 58.0 mg (68%);
mp 52–558C; R =0.17 (petroleum ether/ethyl acetate 70/
f
À1
1
3
30); IR (ATR): n=3414, 2976, 1757, 1728, 1459, 1231, 1182,
693 cm ; H NMR (600 MHz, MeOH-d ): d=6.93 (d, J=
4
Adv. Synth. Catal. 2014, 356, 1007 – 1020
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1017