Efficient One-Pot Synthesis of Multi-Substituted Dihydrofurans
2,6,6-Trimethyl-4-oxo-2,3,4,5,6,7-hexahydrobenzofuran-2-
3.72–3.60 (m, 2H), 2.51–2.42 (m, 2H), 2.35–2.30 (m, 2H),
2.09–1.99 (m, 4H); 13C NMR (75 MHz, CDCl3): d=194.8,
177.2, 113.3, 112.5, 67.5, 43.5, 36.3, 30.0, 23.4, 21.3.
yl acetate (7):[30a,32b] Yellow oil; IR (neat): n=2961, 1767,
1671, 1424, 1362, 1193, 1059, 865, 698 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d=3.23 (s, 2H), 2.46 (s, 2H), 2.28 (s,
2H), 2.13 (s, 3H), 2.07 (s, 3H), 1.05 (s, 6H); 13C NMR
(75 MHz, CDCl3): d=204.6, 198.0, 167.3, 165.0, 121.7, 50.4,
42.4, 37.6, 32.8, 29.3, 28.0, 20.7.
4,4a,6,7,8,9a-Hexahydro-2H-pyranoACTHNUTRGNEUNG[2,3-b]benzofuran-
5(3H)-one (15):[19a–c,37c] Yellow oil; IR (neat): n=2949, 1728,
1
1634, 1403, 1234, 1145, 1079, 918, 829, 770 cmÀ1; H NMR
(300 MHz, CDCl3): d=5.87 (d, J=7.8 Hz, 1H), 3.79–3.64
(m, 2H), 3.08–3.00 (m, 1H), 2.50–2.37 (m, 2H), 2.29 (dd, J=
7.2, 5.4 Hz, 2H), 1.99 (dd, J=6.6, 6.0 Hz, 2H), 1.92–1.44 (m,
4H); 13C NMR (75 MHz, CDCl3): d=195.4, 176.4, 116.1,
106.6, 60.5, 36.5, 35.0, 23.6, 21.5, 20.3, 19.1.
6,6-Dimethyl-1-phenylspiro
N
(8):[33]
Yellow solid; mp 122–1238C; IR (KBr): n=2955, 2872,
1
1676, 1384, 1337, 1274, 1219, 1079, 781, 641 cmÀ1; H NMR
(300 MHz, CDCl3): d=7.25–7.13 (m, 5H), 3.19 (t, J=
9.0 Hz, 1H), 2.60–2.44 (m, 3H), 2.31–2.12 (m, 3H), 1.06 (s,
3H), 0.97 (s, 3H); 13C NMR (75 MHz, CDCl3): d=205.8,
201.7, 133.1, 129.5, 128.8, 128.0, 127.9, 54.0, 53.2, 48.6, 48.5,
30.5, 29.3, 27.8, 22.1.
4-Oxo-2,3,4,5,6,7-hexahydrobenzofuran-2-yl
(16):[15,29a,32b] Yellow oil; IR (neat): n=2951, 1760, 1649,
1407, 1216, 1165, 1053, 938, 872, 775 cmÀ1 1H NMR
acetate
;
(300 MHz, CDCl3): d=6.67 (d, J=7.5 Hz, 1H), 3.01 (dd, J=
16.2, 6.6 Hz, 1H), 2.75 (d, J=16.2 Hz, 1H), 2.52–2.46 (m,
2H), 2.35–2.31 (m, 2H), 2.07 (s, 3H), 2.04–1.98 (m, 2H);
13C NMR (75 MHz, CDCl3): d=195.2, 175.3, 169.4, 112.2,
98.5, 36.4, 31.9, 23.4, 21.5, 20.9.
6,6-Dimethyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-
4(5H)-one (9):[15,29a,32,34] Yellow oil; IR (neat): n=3064, 2959,
1640, 1403, 1220, 1165, 1045, 961, 758, 701, 628 cmÀ1
;
1H NMR (300 MHz, CDCl3): d=7.35–7.23 (m, 5H), 5.70
(dd, J=10.2, 7.5 Hz, 1H), 3.27–3.18 (m, 1H), 2.83–2.77 (m,
1H), 2.31 (s, 2H), 2.06 (s, 2H), 1.08 (s, 6H); 13C NMR
(75 MHz, CDCl3): d=194.8, 176.1, 140.6, 128.8, 128.5, 125.8,
111.4, 86.5, 50.9, 37.7, 34.1, 33.8, 28.8, 28.5.
2-Phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(17):[15,29a,34b,37c] Yellow oil; IR (neat): n=3032, 2948, 1634,
1495, 1454, 1402, 1289, 1231, 1182, 1061, 1022, 997, 907, 760,
700 cmÀ1 1H NMR (300 MHz, CDCl3): d=7.32–7.21 (m,
;
6,6-Dimethyl-2-(prop-1-en-2-yl)-2,3,6,7-tetrahydrobenzo-
5H), 5.66 (dd, J=10.5, 8.1 Hz, 1H), 3.23–3.14 (m, 1H),
2.81–2.73 (m, 1H), 2.45–2.39 (m, 2H), 2.32–2.28 (m, 2H),
2.02–1.94 (m, 2H); 13C NMR (75 MHz, CDCl3): d=195.6,
177.5, 140.4, 128.6, 128.3, 125.7, 112.8, 86.2, 36.2, 33.7, 23.7,
21.5; HR-MS: m/z=214.1001 [M+], calcd. for C14H14O2:
214.0994.
furan-4(5H)-one (10):[10b,11c,35] Yellow oil; IR (neat): n=2957,
2873, 1637, 1402, 1244, 1165, 1144, 1026, 907, 758, 639 cmÀ1
;
1H NMR (300 MHz, CDCl3): d=4.90, (s, 1H), 4.76 (s, 1H),
2.76 (d, J=14.7 Hz, 1H), 2.55 (d, J=14.4 Hz, 1H), 2.23 (s,
2H), 2.15 (s, 2H), 1.69 (s, 3H), 1.43 (s, 3H), 1.04 (s, 3H),
1.02 (s, 3H); 13C NMR (75 MHz, CDCl3): d=194.8, 175.0,
146.4, 110.9, 110.0, 93.5, 50.7, 37.8, 37.2, 34.0, 28.7, 28.3, 26.0,
18.2. HR-MS: m/z=220.1464 [M+], calcd. for C14H20O2:
220.1463.
2-Methyl-4-oxo-2,3,4,5,6,7-hexahydrobenzofuran-2-yl ace-
tate (18):[32b] Yellow oil; IR (neat): n=2955, 1767, 1672,
1427, 1361, 1199, 1067, 910, 846, 711 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d=3.20 (s, 2H), 2.56 (dd, J=6.0, 5.7 Hz,
2H), 2.39 (dd, J=6.9, 5.7 Hz, 2H), 2.12 (s, 3H), 2.04 (s,
3H), 2.00–1.96 (m, 2H); 13C NMR (75 MHz, CDCl3): d=
204.6, 197.9, 167.1, 166.8, 122.7, 37.7, 36.4, 29.2, 28.5, 20.7,
20.6.
Methyl 2,6,6-trimethyl-4-oxo-2,3,4,5,6,7-hexahydrobenzo-
furan-2-carboxylate (11):[15,32a,36] Yellow oil; IR (neat): n=
2956, 1741, 1644, 1450, 1402, 1237, 1172, 1030, 918, 813,
1
629 cmÀ1; H NMR (300 MHz, CDCl3): d=3.75 (s, 3H), 3.14
(d, J=14.7 Hz, 1H), 2.72 (d, J=14.7 Hz, 1H), 2.31 (d, J=
10.1 Hz, 2H), 2.20 (s, 2H), 1.62 (s, 3H), 1.07 (s, 6H);
13C NMR (75 MHz, CDCl3): d=194.6, 175.0, 172.3, 110.8,
89.3, 52.9, 50.9, 37.6, 37.1, 34.2, 28.7, 28.5, 24.6.
2-Methyl-6,7-dihydrobenzofuran-4(5H)-one
Yellow oil; IR (neat): n=2950, 1676, 1584, 1433, 1358, 1238,
1123, 1055, 1011, 938, 893, 811.8, 7.9, 641 cmÀ1 1H NMR
(19):[38]
;
(300 MHz, CDCl3): d=6.14 (s, 1H), 2.74 (dd, J=6.3, 6.0 Hz,
2H), 2.37 (dd, J=6.6, 6.0 Hz, 2H), 2.20 (s, 3H), 2.10–2.04
(m, 2H); 13C NMR (75 MHz, CDCl3): d=194.5, 165.9, 152.4,
121.8, 101.7, 37.4, 23.1, 22.5, 13.2.
2-Ethoxy-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(12):[29a,37] Yellow oil; IR (neat): n=2949, 1722, 1632, 1406,
1245, 1180, 1112, 903, 742 cmÀ1
;
1H NMR (300 MHz,
CDCl3): d=5.64–5.60 (m, 1H), 3.82–3.72 (m, 1H), 3.56–3.46
(m, 1H), 2.81 (dd, J=15.9, 7.2 Hz, 1H), 2.53 (dd, J=15.6,
1.5 Hz, 1H), 2.37–2.30 (m, 2H), 2.21 (uneven t, J=6.6,
6.3 Hz, 2H), 2.01–1.87 (m, 2H), 1.12 (t, J=6.3 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=195.1, 175.7, 112.0, 108.3,
64.8, 36.1, 32.5, 23.6, 21.3, 14.7.
6-Methyl-4-oxo-2,3,4,5,6,7-hexahydrobenzofuran-2-yl ace-
tate (20):[15,32b] 1:1 mixture of diastereomers; yellow oil; IR
(neat): n=2928, 1736, 1633, 1404, 1205, 1142, 1049,
736 cmÀ1 1H NMR (300 MHz, CDCl3): d=6.70–6.66 (m,
;
1H), 3.04–2.97 (m, 1H), 2.77–2.70 (m, 1H), 2.52–2.48 (m,
2H), 2.43–2.34 (m, 2H), 2.07 (s, 3H), 2.06–2.03 (m, 1H),
1.09–1.06 (m, 3H); 13C NMR (75 MHz, CDCl3): d=194.9,
175.0, 169.4, 111.9, 98.7, 45.0, 31.9, 31.5, 31.3, 29.8, 20.9; HR-
MS: m/z=210.0894 [M+], calcd. for C11H14O4: 210.0892.
6-Methyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-
one (21):[15,19d,29a] 1:1 mixture of diastereomers; yellow oil;
IR (neat): n=3034, 2957, 1634, 1495, 1454, 1402, 1248, 1211,
2-Methoxy-2-methyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-
one (13):[30] Yellow oil; IR (neat): n=2949, 1713, 1640, 1384,
1
1268, 1185, 1104, 1044, 835, 742, cmÀ1; H NMR (300 MHz,
CDCl3): d=3.19 (s, 3H), 2.78 (d, J=15.6 Hz, 1H), 2.59 (d,
J=15.6 Hz, 1H), 2.37 (s, 2H), 2.27 (dd, J=5.47, 5.4 Hz,
2H), 2.00–1.94 (m, 2H), 1.53 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=195.3, 175.5, 114.9, 112.5, 50.1, 36.1, 35.5, 24.7,
23.5, 21.4.
1138, 1053, 1028, 924, 901, 760, 700 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d=7.33–7.18 (m, 5H), 5.71–5.64 (m,
1H), 3.24–3.13 (m, 1H), 2.82–2.72 (m, 1H), 2.52–2.45 (m,
1H), 2.41–2.23 (m, 2H), 2.17–2.04 (m, 2H), 1.05 (d, J=
6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=195.5, 177.4,
3,3a,5,6,7,8a-HexahydrofuroACTHNUTRGNEUGN[2,3-b]benzofuran-4(2H)-one
(14):[29a,34] Yellow oil; IR (neat): n=2949, 1713, 1640, 1384,
1
1268, 1185, 1104, 1044, 835, 742 cmÀ1; H NMR (300 MHz,
CDCl3): d=6.22 (d, J=5.9 Hz, 1H), 4.18–4.04 (m, 1H),
Adv. Synth. Catal. 2013, 355, 2361 – 2374
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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