9134
N. Fonteneau et al. / Tetrahedron 57 22001) 9131±9135
430.0 g, 217.4 mmol) and POCl3 416.7 g, 108.7 mmol). The
resulting mixture was stirred at 608C for 3 h. The reaction
was quenched with ice, and extracted with dichloromethane.
Flash column chromatography 4petroleum ether/ether, 97:3)
445 ml) was added sodium acetate 4275 mg). The resulting
mixture was re¯uxed for 16 h and then quenched with ice.
The precipitate was ®ltrated, dried to provide 10 as a white
solid: mp 194±1968C, lit.21 196±1978C; 1H NMR 4300
MHz, CDCl3): d 2.41 4m, 9H), 6.78 4s, 1H), 6.93 4dd, 1H,
J8, 2 Hz), 7.13 4s, 1H), 7.31 4dd, 1H, J8, 2 Hz), 7.62 4t,
1H, J8 Hz); 13C NMR 4300 MHz, CDCl3): d 21.2, 21.9,
112.9, 115.2, 115.7, 115.8, 118.3, 119.6, 134.3, 146.4,
149.7, 150.0, 156.4, 156.5, 169.7, 169.8 and 174.2;HRMS
4M1) calcd 326.0790, found 326.0792.
1
afforded 5 410%): mp 1348C, lit.20 142±1438C; H NMR
4300 MHz, CDCl3): d 2.32 4s, 3H), 6.47 4s, 1H), 6.55 4s,
1H), 7.27 4dd, 1H, J7.8, 7.2 Hz), 7.30 4d, 1H, J8.2 Hz),
7.62 4ddd, 1H, J8.2, 7.2, 1.3 Hz), 8.11 4dd, 1H, J7.8,
1.3 Hz), 12.41 4s, OH); 13C NMR 4300 MHz, CDCl3): d
23.0, 107.2, 107.8, 111.5, 118.2, 120.8, 124.2, 126.1,
135.6, 149.2, 156.31, 156.35, 161.8 and 182.0.
4.3.6. 3-01,8-Diacetoxy-9-oxo-xanthene)carboxylic acid
011). To a solution of 10 4165 mg, 0.5 mmol) in acetic
acid 44.8 ml) and acetic anhydride 44.8 ml) was added, at
658C during 30 min, a solution of chromium trioxide
4435 mg, 4.35 mmol) in water 40.6 ml) and acetic acid
44.8 ml). The resulting mixture was stirred at 808C for
14 h and then quenched with water. After 4 h at 48C, the
precipitate was ®ltrated, washed and dried to provide 11
4.3.2. 1-Acetoxy-3-methyl-9-oxo-xanthene 06). To a
solution of 5 4100 mg, 0.44 mmol) in acetic anhydride
45 ml) was added sodium acetate 450 mg, 0.61 mmol). The
resulting mixture was stirred at 508C for 15 h and then
quenched with ice. The precipitate was ®ltrated, washed
and dried. Flash column chromatography 4EtOAc/petro-
leum ether, 10:90) provided 6 495%): mp 1508C, lit.20
1
1
153±1548C; H NMR 4300 MHz, CDCl3): d 2.49 4s, 6H),
482 mg, 45%) as a white solid: mp 181±1838C; H NMR
6.82 4sl, 1H), 7.20 4sl, 1H), 7.35 4ddd, 1H, J7.9, 7.2,
1.0 Hz), 7.42 4dl, 1H, J8.4 Hz), 7.69 4ddd, 1H, J8.4,
7.2, 1.5 Hz), 8.23 4dd, 1H, J7.9, 1.5 Hz); 13C NMR 4300
MHz, CDCl3): d 21.9, 21.2, 112.7, 116.1, 117.6, 119.4,
124.0, 122.2, 126.5, 134.2, 146.4, 149.8, 155.3, 157.3,
169.9 and 175.6.
4300 MHz, DMSO d6): d 2.45 and 2.50 42s, 6H), 6.98 4sl,
1H), 7.12 4dl, 1H, J8 Hz), 7.37 4sl, 1H), 7.53 4dl, 1H, J
8 Hz), 7.84 4t, 1H, J8 Hz), 9.00±11.00 4sl, 1H); 13C NMR
4300 MHz, CDCl3): d 21.0, 21.4, 115.4, 116.1, 118.9, 120.1,
135.5, 155.9, 156.0, 169.2 and 173.6;HRMS 4FAB) m/z
4M1) calcd 356.0532, found 356.0560.
4.3.3. 3-01-Acetoxy-9-oxo-xanthene)carboxylic acid 07).
To a solution of 6 450 mg, 0.17 mmol) in glacial acetic
acid 41.5 ml) and acetic anhydride 41.5 ml) was added, at
50±608C and during 30 min, a solution of chromium tri-
oxide in 0.2 ml of water and 1.5 ml of acetic acid. The
resulting mixture was stirred at 65±708C for 3 h and then
quenched with water. The precipitate was ®ltrated, washed
with water and dried under vacuum to provide 7 437%): mp
4.3.7. 1,3,8-Trihydroxy-9-oxo-xanthene 012). To a solu-
tion of 2,6-dihydroxybenzoic acid 41.00 g, 6.48 mmol) and
phloroglucinol 40.82 g, 6.48 mmol) was added ZnCl2
42.65 g, 19.44 mol) and POCl3 411 ml). The resulting
mixture was heated at 65±708C for 6.5 h. The reaction
was quenched with ice and extracted with EtOAc. Flash
column chromatography 4EtOAc/petroleum ether, 20:80)
afforded 12 40.45 g, 29%) as a white solid: mp 269±
1
1
2088C; H NMR 4300 MHz, CDCl3): d 2.43 4s, 3H), 7.50
2708C, lit.22 2588C; H NMR 4300 MHz, 4CD3)2CO): d
4dd, 1H, J7.2, 7.9 Hz), 7.62 4sl, 1H), 7.66 4d, 1H, J
8.3 Hz), 7.89 4ddd, 1H, J8.3, 7.2, 1.5 Hz), 8.08 4sl, 1H),
8.20 4dd, 1H, J7.9, 1.5 Hz).
6.24 4d, 1H, J2.3 Hz), 6.37 4d, 1H, J2.3 Hz), 6.72 and
6.88 42dd, 2H, J8.4, 0.9 Hz), 7.64 4t, 1H, J8.4 Hz), 10.00
4sl, OH), 11.82 4s, 2OH); 13C NMR 4300 MHz, 4CD3)2CO):
d 94.3, 98.5, 101.7, 107.0, 109.6, 110.6, 137.1, 156.0, 158.0,
161.2, 163.2, 166.4 and 184.4;HRMS 4FAB) m/z 4M1H1)
calcd 245.0450, found 245.0465.
4.3.4. 1,8-Dihydroxy-3-methyl-9-oxo-xanthene 08). A
mixture of 2,6-dihydroxybenzoic acid 41.00 g, 6.49
mmol), 3,5-dihydroxytoluene 40.92 g, 6.49 mmol) and
polyphosphoric acid 410.00 g) was heated at 80±908C for
4 h. The resulting mixture was quenched with ice and
extracted with EtOAc. Flash column chromatography
4EtOAc/petroleum ether, 5:95±30:70) afforded 8 40.16 g,
10%) and 9 40.47 g, 30%).
4.3.8. 3-Tri¯uoromethanesulfonyloxy-1,8-dihydroxy-9-
oxo-xanthene 013). To
a solution of 12 4400 mg,
1.64 mmol) in dichloromethane 416 ml) was added pyridine
40.53 ml, 6.55 mmol) and then tri¯uoromethanesulfonic
anhydride 40.27 ml, 1.64 mmol). After 2 h at 08C, the result-
ing mixture was quenched with 1N aqueous HCl and
extracted with EtOAc. Flash column chromatography
4EtOAc/petroleum ether, 2:98±50:50) afforded 13 4465
21
1
8: mp 189±1918C;lit. 193±1948C, H NMR 4300 MHz,
CDCl3): d 2.41 4s, 3H), 6.59 4s, 1H), 6.69 4s, 1H), 6.77 4dd,
1H, J8, 2 Hz), 6.86 4dd, 1H, J8, 2 Hz), 7.56 4t, 1H, J
8 Hz), 11.86 and 11.70 42s, 2OH); 13C NMR 4300 MHz,
CDCl3): d 22.7, 105.8, 107.1, 107.7, 107.8, 110.7, 111.6,
137.2, 149.9, 156.2, 156.3, 161.0, 161.4 and 185.7;HRMS
4M1) calcd 242.0579, found 242.0579.
1
mg, 75%): mp 106±1088C; H NMR 4300 MHz, CDCl3):
d 6.69 4d, 1H, J2.3 Hz), 6.84 4d, 1H, J2.3 Hz), 6.81 and
6.89 42dd, 2H, J8.3, 0.9 Hz), 7.62 4t, 1H, J8.4 Hz), 11.47
and 12.07 42s, 2OH); 13C NMR 4300 MHz, CDCl3): d 100.9,
104.4, 107.2, 107.6, 111.8, 116.5, 138.2, 154.6, 155.9,
156.7, 161.3, 163.0 and 185.2.
1
9: H NMR 4300 MHz, CDCl3): d 2.76 4s, 3H), 6.66±6.69
4m, 3H), 6.83 4dd, 1H, J8, 2 Hz), 7.56 4t, 1H, J8 Hz),
4.3.9. 3-Tri¯uoromethanesulfonyloxy-1,8-dipivaloyloxy-
9-oxo-xanthene 014). To a solution of 13 4399 mg,
1.06 mmol) in pyridine 45 ml) was added pivaloyl chloride
40.32 ml, 2.65 mmol) at 08C. The resulting mixture was
stirred at room temperature for 48 h. The reaction was
9.80 4s, OH), 13.18 4s, OH).
4.3.5. 1,8-Diacetoxy-3-methyl-9-oxo-xanthene 010). To a
solution of 8 4200 mg, 0.82 mmol) in acetic anhydride