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DOI: 10.1055/s-0029-1219532
Michael-Type Adducts of 3-Carbethoxycoumarins via Diels-Alder Reaction: Tandem Ring Construction of Furopyranochroman-2-one Skeletons
Publication History
Publication Date:
18 February 2010 (online)
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Abstract
Diels-Alder reaction of furan with electron-deficient 3-carbethoxycoumarins gave the Michael-type adducts obtained from the rearrangement of the intermediate Diels-Alder adducts, instead of the Diels-Alder cycloadducts. Trapping of the dipolar intermediate with electron-deficient aromatic aldehydes gave a one-pot access to fused furo[3,2-b]pyranochroman-2-ones with multiple stereogenic centers. Ring opening of the lactone moiety gave a facile route to generate diverse scaffolds.
Key words
coumarins - substituted furans - fused furopyranochroman-2-ones - Michael products - Diels-Alder reaction - MCR - scaffold hopping reaction
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References and Notes
General Synthetic
Procedure for 5a-f
To a mixture of 3-carbethoxycoumarin 1a-f (3
mmol) and furan 2 (30 mmol), AlCl3 catalyst
(10 mol%) was added and stirred at r.t. for 20-26
h. After the completion of reaction, excess of furan was distilled
off, diluted with H2O and extracted with CH2Cl2 (3 × 25
mL). The combined extracts were dried over anhyd Na2SO4,
filtered, evaporated under reduced pressure, and purified by column
chromatography on silica gel (hexane-EtOAc). This was further
recrystal-lized from CH2Cl2 to afford 5a-f.
5a: White solid; yield 83%; mp
56-58 ˚C. ¹H NMR
(400 MHz, CDCl3): δ = 7.37-7.30
(m, 3 H), 7.12-7.09 (m, 2 H), 6.28-6.23 (m, 1
H), 6.06 (d, J = 2.4
Hz, 1 H), 4.8 (d, J = 5.6 Hz,
1 H), 4.19-4.12 (m, 3 H), 1.10 (t, J = 7.2
Hz, 3 H).
¹³C NMR (400 MHz,
CDCl3): δ = 166.3, 163.7, 150.9, 143.0, 129.5,
128.5, 127.3, 125.0, 121.4, 117.1, 110.4, 108.0, 62.3, 51.1, 38.6,
13.8. FTIR (KBr pellet): 3142, 3123, 2945, 1770, 1732, 1614, 1487,
1460, 1222, 1161, 1012, 935, 756, 661, 570, 524 cm-¹.
HRMS (EI): m/z calcd for C16H14O5 [M+]: 286.0899;
found: 286.0903.
5b: White solid;
yield 78%; mp 80-82 ˚C. ¹H
NMR (400 MHz, CDCl3): δ = 7.45-7.38
(m, 3 H), 7.20 (d, J = 2.4
Hz, 1 H), 6.99-6.93 (m, 1 H), 6.30-6.26 (m, 1
H), 6.10 (d, J = 3.2 Hz,
1 H), 4.18-4.11 (m, 3 H), 1.14 (t, J = 7.2
Hz, 3 H). ¹³C NMR (400 MHz, CDCl3): δ = 166.1,
163.0, 150.2, 150.0, 143.5, 132.7, 131.4, 123.6, 119.0, 117.7, 110.7,
108.4, 62.7, 50.8, 38.4, 14.3. FTIR (neat): 3319, 2982, 1780, 1739,
1602, 1477, 1408, 1371, 1319, 1265, 1222, 1153, 1116, 1072, 1014,
904, 819, 742 cm-¹. HRMS (EI): m/z calcd for C16H13O5Br [M+]:
365.0023; found: 365.0029.
Synthesis
of Diels-Alder Adduct 7
To a mixture of 3-carbethoxycoumarin 1a (1 mmol) and cyclopentadiene (6, 1 mmol) in CH2Cl2 (20
mL), AlCl3 catalyst (10 mol%) was added and
stirred at r.t. for 4 h. After the completion of reaction, the reaction
mixture was washed with H2O (2 × 5
mL), brine (5 mL), dried over anhyd Na2SO4,
concentrated over reduced pressure, and purified by column chromatography
to afford 7.
7:
Light-yellow liquid; yield 60%. ¹H
NMR (400 MHz, CDCl3): δ = 7.28-6.96
(m, 4 H), 6.22 (dd, J = 2.8,
5.6 Hz, 1 H), 5.95 (dd, J = 2.8,
5.6 Hz, 1 H), 4.26-4.13 (m, 2 H), 3.79-3.72 (m,
1 H), 3.62 (d, J = 3.6
Hz, 1 H), 2.03 (d, J = 5.6
Hz, 1 H), 1.93 (d, J = 8.0
Hz, 1 H), 1.68 (d, J = 8.0
Hz, 1 H), 1.28-1.23 (m, 3 H). ¹³C
NMR (400 MHz, CDCl3): δ = 171.0, 165.9,
149.5, 138.1, 136.5, 128.6, 128.1, 124.8, 121.2, 117.0, 62.1, 58.1,
52.9, 50.4, 47.4, 30.9, 13.6. FTIR (neat): 3046, 2924, 2851, 1781,
1739, 1615, 1488, 1456, 1363, 1224, 1157, 1080, 968, 756 cm-¹.
HRMS (EI): m/z calcd for C17H16O4 [M+]:
284.1023; found: 284.1026.
Synthesis
of 10a
To a mixture of 3-carbethoxycoumarin (1a, 3 mmol) and furan (2,
30 mmol) at 10 ˚C, 3-chlorobenzaldehyde (3 mmol),
and AlCl3 (10 mol%) were added and stirred for
24 h. After completion of the reaction, excess of furan was distilled
off, diluted with H2O, and extracted with CH2Cl2 (3 × 25
mL). The combined extracts were dried over anhyd Na2SO4,
filtered, evaporated under reduced pressure, and purified by column
chromatography on silica gel (hexane-EtOAc) to afford 10a.
10a:
Colorless liquid; yield 68%. ¹H NMR
(400 MHz, CDCl3): δ = 7.35-7.11
(m, 9 H), 6.30 (d, J = 8.0
Hz, 1 H), 6.06 (d, J = 4.0
Hz, 1 H), 5.97-5.89 (m, 1 H), 5.35 (s, 1 H), 4.80 (d, J = 4.0 Hz,
1 H), 4.17-4.10 (m, 2 H), 1.13-1.10 (m, 3 H). ¹³C
NMR (400 MHz, CDCl3): δ = 167.2, 163.7,
151.9, 142.7, 134.4, 128.6, 128.2, 124.8, 123.3, 121.4, 117.3, 110.3,
108.5, 107.8, 106.9, 106.3, 62.3, 51.1, 44.6, 38.6, 34.4, 30.9,
13.8. FTIR (neat): 3121, 3065, 2984, 2926, 1772, 1743, 1591, 1487,
1456, 1371, 1219, 1149, 1107, 1014, 941, 760, 686 cm-¹.
HRMS (EI): m/z calcd for C23H19O6Cl [M+]: 426.0916;
found: 426.0913.
10b: Colorless
liquid; yield 62%. ¹H NMR (400 MHz, CDCl3): δ = 8.21-8.17
(m, 2 H), 7.13-7.09 (m, 7 H), 6.40 (s, 1 H), 6.05 (d, J = 4.0 Hz,
1 H), 5.45 (s, 1 H), 4.15-4.12 (m, 2 H), 3.05-3.01
(m, 2 H), 1.25-1.19 (m, 3 H). ¹³C
NMR (400 MHz, CDCl3): δ = 166.8, 163.3,
153.0, 152.1, 150.9, 146.3, 142.3, 129.0, 128.3, 127.9, 124.4, 122.8,
121.0, 117.1, 109.0, 107.6, 62.2, 51.0, 44.5, 38.5, 34.6, 33.8,
29.5. FTIR (neat): 3121, 3078, 2921, 2850, 1774, 1740, 1593, 1487, 1456,
1348, 1218, 1148, 1015, 773 cm-¹. HRMS
(EI): m/z calcd for C23H19NO8 [M+]:
437.1124; found: 437.1129.
General
Synthetic Procedure for 11a-f
To the 3-carbethoxy-4-(2-furanyl)chroman-2-one 5a-f (1 mmol)
a solution of NaOH (3 mmol) in H2O (15 mL) was added
and stirred at 80 ˚C for 4 h. The reaction mixture
was neutralized with concd HCl and heated at 80 ˚C for
2-4 h (Table
[²]
).
The reaction mixture was cooled, extracted with CH2Cl2 (3 × 25
mL). The combined extracts were concentrated to dryness and recrystallized
from CH2Cl2.
11a: White solid; yield 86%; mp 141-143 ˚C. ¹H
NMR (400 MHz, CDCl3): δ = 7.33 (s,
1 H), 7.15-7.06 (m, 2 H), 6.90-6.83 (m, 2 H),
6.30 (d, J = 1.2
Hz, 1 H), 6.12 (d, J = 2.4
Hz, 1 H), 4.84 (t, J = 7.2
Hz, 1 H), 3.23-3.08 (m, 2 H). ¹³C
NMR (400 MHz, CDCl3/CD3OD): δ = 174.5,
156.0, 153.8, 141.0, 127.6, 124.5, 119.6, 116.9, 115.5, 109.7, 105.5,
38.0, 34.3. FTIR (KBr pellet): 3443, 3148, 2991, 2604, 1676, 1593, 1502,
1456, 1334, 1307, 1211, 1161, 1093, 1008, 943, 823, 758, 742, 638,
596, 530, 497 cm-¹. HRMS (EI): m/z calcd for C13H12O4 [M+]:
232.0829; found: 232.0825.