The Journal of Organic Chemistry
Article
solution of n-BuLi (2.5 M in hexane, 23.80 mL, 59.54 mmol)
Synthesis of Compound 14. To a stirred solution of silyltriflate 1b
(492.6 mg, 1.20 mmol) and methyl salicylate (152.2 mg, 1.00 mmol)
in MeCN (10 mL) was added CsF (607.6 mg, 4.00 mmol). The
solution was stirred at 65 °C for 24 h, then cooled to room
temperature, and filtered over silica gel (CH Cl eluent). Evaporation
dropwise over 1.5 h. Et NH (6.60 mL, 63.80 mmol) was added, and
2
the resulting mixture was stirred at −78 °C for 30 min and then
allowed to warm to room temperature over 30 min. Next, Comins’
reagent (23.38 g, 59.54 mmol) was added. The mixture was allowed
2
2
to stir for 16 h at room temperature. Aqueous NaHCO (5%, 50 mL)
under reduced pressure afforded the crude product, which was further
purified by flash chromatography (5/1 PE/CH Cl ) to afford
3
was added, and the mixture was extracted with EtOAc (300 mL × 3).
The combined organic layers were washed with brine and dried over
Na SO , filtered, and concentrated under reduced pressure.
2
2
xanthone 14 (212.1 mg, 69%) as a pale yellow solid.
1
Mp 196.9−197.6 °C H NMR (400 MHz, CDCl ): δ 8.28 (dd, J =
2
4
3
Purification of the crude product by flash column chromatography
8.0 Hz, 1.6 Hz, 1H), 7.64−7.59 (m, 1H), 7.38 (d, J = 8.0 Hz, 1H),
7.31 (t, J = 8.0 Hz, 1H), 6.88 (d, J = 10.0 Hz, 1H), 6.30 (s, 1H), 5.60
(d, J = 10.0 Hz, 1H), 3.98 (s, 3H), 1.50 (s, 6H) C{ H} NMR (101
(
PE) afforded compound 1b (17.17 g, 98%) as a white solid. Mp
1
13
1
4
1
6
1
7
1
5.6−45.7 °C H NMR (400 MHz, CDCl ): δ 6.49 (d, J = 10.0 Hz,
3
H), 6.48 (s, 1H), 5.55 (d, J = 10.0 Hz, 1H), 3.80 (s, 3H), 1.42 (s,
MHz, CDCl ): δ 175.4, 161.7, 158.8, 154.6, 153.7, 133.6, 127.0,
3
H), 0.43 (s, 9H) 13C{ H} NMR (101 MHz, CDCl ): δ 153.4, 151.0,
1
126.7, 123.8, 122.8, 116.8, 115.4, 106.9, 102.2, 95.5, 78.1, 56.3, 28.2
3
36.7, 132.0, 127.8, 122.4, 118.9 (q, JC‑F = 321.4 Hz), 118.7, 102.8,
IR (KBr): νmax 2970, 1724, 1654, 1629, 1489, 1465, 1423, 1383, 1357,
1304, 1087, 754 cm HRMS-ESI (m/z): [M + H]+ calcd for
−1
5.6, 55.6, 27.4, 1.6 IR (KBr): ν 2976, 1596, 1410, 1316, 1200,
max
−
1
+
+
4
160, 1130, 921, 864, 843 cm HRMS-ESI (m/z): [M + H] calcd
C H O 309.1121, found 309.1125.
1
9
17
+
for C H F O SSi 411.0904, found 411.0908.
Synthesis of Compound 15. Ethyl diazoacetate (171.1 mg, 1.50
16
22
3
5
Synthesis of Compound 11. To a stirred solution of silyltriflate 1b
1.64 g, 4.00 mmol) and 2,5-dimethylfuran (1.27 mL, 12.0 mmol) in
mmol) was added to a solution of silyltriflate 1b (738.9 mg, 1.80
mmol), KF (261.5 mg, 4.25 mmol), and 18-crown-6 (1.39 g, 5.25
mmol) in THF (7.2 mL) under a N2 atmosphere. The reaction
mixture was stirred at room temperature for 18 h, then filtered
through a short pad of Celite, and eluted with EtOAc. The filtrate was
concentrated, and the residue was purified by chromatography (7/1
(
MeCN (20 mL) was added CsF (1.82 g, 12.0 mmol). The solution
was stirred at room temperature for 12 h and then filtered over silica
gel (CH Cl eluent). Evaporation under reduced pressure afforded
2
2
the crude product, which was further purified by flash chromatog-
raphy (150/1 PE/EtOAc) to afford compound 11 (1.09 g, 96%) as
PE/EtOAc) to afford compound 15 (343.5 mg, 76%) as a white solid.
1
1
pale yellow viscous oil. H NMR (400 MHz, CDCl ): δ 6.84 (d, J =
Mp 182.6−182.9 °C H NMR (400 MHz, CDCl ): δ 11.31 (brs, 1H),
3
3
5.6 Hz, 1H), 6.72 (d, J = 5.6 Hz, 1H), 6.58 (d, J = 10.0 Hz, 1H), 6.08
7.68 (d, J = 10.0 Hz, 1H), 6.41 (s, 1H), 5.52 (d, J = 10.0 Hz, 1H),
4.45 (q, J = 7.2 Hz, 2H), 3.92 (s, 3H), 1.46 (s, 6H), 1.41 (t, J = 7.2
(
s, 1H), 5.55 (d, J = 10.0 Hz, 1H), 3.72 (s, 3H), 1.98 (s, 3H), 1.96 (s,
1
3
1
13
1
3
1
8
1
H), 1.41 (s, 3H), 1.38 (s, 3H) C{ H} NMR (101 MHz, CDCl ): δ
Hz, 3H) C{ H} NMR (101 MHz, CDCl ): δ 162.9, 150.5, 145.2,
3
3
53.1, 152.5, 150.7, 147.8, 145.7, 130.2, 129.1, 118.0, 110.1, 97.8,
125.9, 121.1, 120.3, 104.9, 99.2, 75.9, 61.1, 55.7, 27.3, 14.2 IR (KBr):
9.6, 88.8, 75.5, 55.4, 27.9, 27.4, 18.3, 17.2 IR (KBr): ν 2976, 2935,
νmax 3158, 2971, 2933, 1712, 1593, 1433, 1295, 1262, 1201, 1135,
max
−
1
−1
+
613, 1477, 1441, 1303, 1197, 1135, 1017, 729 cm HRMS-ESI (m/
1102, 1035, 984, 762 cm HRMS-ESI (m/z): [M + Na] calcd for
+
+
3
+
z): [M + H] calcd for C H O 285.1485, found 285.1492.
C H N NaO 325.1159, found 325.1163.
1
8
21
16 18
2
4
Synthesis of Compound 12. To a stirred solution of silyltriflate 1b
410.5 mg, 1.00 mmol) and N-methylaniline (160.7 mg, 1.50 mmol)
in MeCN (5 mL) was added CsF (455.7 mg, 3.00 mmol). The
mixture was stirred at room temperature for 18 h and then filtered
over silica gel (EtOAc eluent). Evaporation under reduced pressure
afforded the crude product, which was further purified by flash
Synthesis of Compound 16. N-tert-butyl-α-phenylnitrone (177.2
mg, 1.00 mmol) was added to a solution of silyltriflate 1b (656.8 mg,
1.60 mmol) and CsF (607.6 mg, 4.00 mmol) in THF (20 mL) under
(
a N atmosphere. The solution was stirred at 65 °C for 16 h, then
2
cooled to room temperature, and filtered over silica gel (CH Cl
2
2
eluent). Evaporation under reduced pressure afforded the crude
product, which was further purified by flash chromatography (20/1
chromatography (200/1 PE/EtOAc) to afford compound 12 (295.0
1
mg, quant.) as a colorless oil. H NMR (400 MHz, CDCl ): δ 7.20−
PE/EtOAc) to afford compound 16 (264.2 mg, 72%) as a white solid.
3
1
7
.16 (m, 2H), 6.74 (t, J = 7.2 Hz, 1H), 6.66 (d, J = 8.0 Hz, 2H), 6.32
Mp 158.8−159.8 °C H NMR (400 MHz, CDCl ): δ 7.36 (d, J = 7.2
3
(
d, J = 2.4 Hz, 1H), 6.27 (d, J = 2.4 Hz, 1H), 6.22 (d, J = 10.0 Hz,
Hz, 2H), 7.28 (t, J = 7.2 Hz, 2H), 7.21 (t, J = 7.2 Hz, 1H), 6.44 (d, J =
10.0 Hz, 1H), 5.91 (s, 1H), 5.52 (s, 1H), 5.43 (d, J = 10.0 Hz, 1H),
3.61 (s, 3H), 1.44 (s, 3H), 1.41 (s, 3H), 1.17 (s, 9H) C{ H} NMR
1H), 5.42 (d, J = 10.0 Hz, 1H), 3.73 (s, 3H), 3.22 (s, 3H), 1.42 (s,
1
3
1
6
H)
1
3
1
C{ H} NMR (101 MHz, CDCl ): δ 161.0, 155.3, 149.3, 145.5,
(151 MHz, CDCl ): δ 155.1, 154.9, 154.5, 143.2, 128.2, 127.4, 127.0,
3
3
1
2
1
28.9, 127.9, 118.7, 117.5, 113.9, 112.6, 105.4, 100.1, 76.0, 55.3, 39.9,
126.1, 116.5, 108.6, 96.9, 92.8, 76.6, 64.9, 61.4, 55.4, 28.0, 27.6, 25.4
7.7 IR (neat): νmax 2975, 1608, 1568, 1500, 1315, 1298, 1197, 1146,
IR (KBr): νmax 2971, 2932, 1637, 1589, 1495, 1454, 1360, 1333, 1197,
−1
+
−1
+
114, 1042, 751, 694 cm HRMS-EI (m/z): [M] calcd for
1119, 1010, 773, 711, 699, 578 cm HRMS-EI (m/z): [M] calcd for
+
+
C H NO 295.1567, found 295.1571.
C H NO 365.1985, found 365.1994.
19
21
2
23 27
3
Synthesis of Compound 13. To a stirred solution of silyltriflate 1b
591.1 mg, 1.44 mmol) and ethyl benzoylacetate (230.7 mg, 1.20
Synthesis of Compound 18. CsF (9.11 g, 60.00 mmol), salicylate
(2.87 g, 15.75 mmol), and precursor 1b (7.30 g, 15.00 mmol) in
freshly distilled THF (300 mL) were stirred at 65 °C for 24 h. The
reaction mixture was allowed to cool to room temperature, diluted
with EtOAc (500 mL), and washed with brine (100 mL × 2). The
aqueous layer was re-extracted with diethyl ether (100 mL × 3). The
organic layers were combined, dried with Na SO , and filtered, and
(
mmol) in MeCN (6 mL) was added CsF (437.5 mg, 2.88 mmol). The
solution was stirred at 80 °C for 1 h and then cooled to room
temperature. The mixture was extracted with brine. The aqueous layer
was back-extracted with EtOAc (10 mL × 3). The organics were
combined and dried over Na SO . After filtration, the residue was
2
4
2
4
concentrated under reduced pressure and purified by flash
the solvent was removed under reduced pressure. The residue was
purified by flash chromatography (15/1 PE/EtOAc) to give
compound 18 (3.84 g, 62%) as a pale yellow solid. Mp 196.5−
chromatography (20/1 PE/EtOAc) to afford compound 13 (325.9
1
mg, 71%) as pale yellow oil. H NMR (400 MHz, CDCl ): δ 7.83 (d,
3
J = 7.2 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.41 (d, J = 7.6 Hz, 2H),
196.6 °C.
1
6
3
.45 (d, J = 10.0 Hz, 1H), 6.41 (s, 1H), 5.61 (d, J = 10.0 Hz, 1H),
.91 (q, J = 7.2 Hz, 2H), 3.60 (s, 3H), 3.58 (s, 2H), 1.46 (s, 6H), 1.01
H NMR (400 MHz, CDCl ): δ 7.87 (dd, J = 8.0, 1.6 Hz, 1H),
3
7.65 (d, J = 7.6 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.31 (t, J = 7.2 Hz,
1H), 7.23 (t, J = 8.0 Hz, 1H), 7.14 (dd, J = 7.6, 1.2 Hz, 1H), 6.95 (d, J
= 10.0 Hz, 1H), 6.37 (s, 1H), 5.59 (d, J = 10.0 Hz, 1H), 5.24 (s, 2H),
1
3
1
(t, J = 7.2 Hz, 3H) C{ H} NMR (101 MHz, CDCl ): δ 197.5,
3
1
1
70.3, 157.8, 155.4, 138.4, 133.0, 129.5, 129.2, 129.0, 128.2, 122.6,
18.6, 114.2, 99.3, 76.3, 60.8, 55.6, 34.5, 27.8, 13.9 IR (KBr): νmax
975, 1730, 1662, 1594, 1472, 1446, 1313, 1196, 1124, 1026, 711,
1
3
1
3.99 (s, 3H), 1.49 (s, 6H) C{ H} NMR (101 MHz, CDCl ): δ
3
2
6
175.2, 160.4, 158.6, 153.5, 148.2, 145.0, 136.3, 128.5, 127.6, 127.0,
126.6, 123.8, 123.1, 117.5, 115.5, 114.5, 107.1, 102.8, 97.0, 78.1, 70.6,
56.3, 28.1 IR (KBr): νmax 3055, 2974, 2950, 2838, 1653, 1633, 1588,
87 cm− HRMS-EI (m/z): [M]+ calcd for C H O 380.1618,
1
+
23 24 5
found 380.1627.
6
771
J. Org. Chem. 2021, 86, 6765−6779