Asymmetric Transformations of γ-Acyloxybutenolides
A R T I C L E S
The organic extracts were dried (MgSO4) and concentrated to afford a
yellow solid. Recrystallization from methylene chloride: petroleum
ether afforded coumarin 39 (1.98 g, 47%) as a tan solid, mp 182-183
°C.
IR (film): 3095, 1742, 1680, 1601, 1553m 1466, 1349, 1285, 1182,
1160, 1118 cm-1. 1H NMR (500 MHz, CDCl3 + DMSO-d6): 9.80 (br
s, 1H), 6.35 (d, J ) 2.2 Hz, 1H), 6.21 (d, J ) 2.2 Hz, 1H), 5.81 (s,
1H), 4.06 (q, J ) 7.1 Hz, 2H), 3.76 (s, 3H), 3.10 (t, J ) 7.6 Hz, 2H),
2.50 (t, J ) 7.6 Hz, 2H), 1.17 (t, J ) 7.1 Hz, 3H). 13C NMR (125
MHz, CDCl3 + DMSO-d6): 172.1, 161.3, 161.0, 158.3, 156.8, 156.0,
109.7, 102.3, 96.3, 95.7, 60.3, 55.6, 33.6, 31.4, 13.9. Anal. Calcd for
C15H16O8: C, 61.63; H, 5.52. Found: C, 61.32; H, 5.57.
4-Carboethoxyethyl)-7-hydroxy-8-iodo-5-methoxycoumarin 40.
To a solution of coumarin 39 (1.70 g, 5.82 mmol) in methylene chloride
(30 mL) was added portionwise iodine monochloride (1.03 g, 6.40
mmol) and the resulting purple solution stirred at room temperature.
After 30 min, the reaction mixture, which had become yellow, was
carefully diluted with petroleum ether (20 mL). The precipitated solid
was collected by suction filtration, washed with 1:1 methylene
chloride: petroleum ether to afford iodide 40 (2.24 g, 92%) as a white
solid, mp 204-205 °C.
(s, 1H), 4.40 (ddd, J ) 9.5, 6.2 and 2.2 Hz, 1H), 4.20 (q, J ) 7.1 Hz,
2H), 3.93 (s, 3H), 3.24 (m, 2H), 3.15 (dd, J ) 18.7 and 9.5 Hz, 1H),
3.02 (dd, J ) 18.7 and 2.2 Hz, 1H), 2.62 (t, J ) 7.7 Hz, 2H), 1.30 (t,
J ) 7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3): 173.3, 172.2, 161.1,
160.2, 159.7, 156.4, 152.5, 111.5, 108.6, 105.8, 105.1, 91.1, 60.8, 56.4,
40.5, 33.8, 32.8, 31.9, 14.3. Anal. Calcd for C19H18O8: C, 61.16; H,
4.84. Found: C, 61.16; H, 5.00.
Aflatoxin B lactone 47. A solution of ester 43 (25 mg, 0.0067 mmol)
in acetic acid (1 mL), water (1 mL) and concentrated hydrochloric acid
(0.5 mL) was stirred at room temperature. After 2 days the solvent
was removed in vacuo to afford the acid 46 (23 mg, 100%) as a white
solid used in subsequent reactions without further purification (judged
1
to be >95:5 46:43 by 500 MHz, H NMR).
1H NMR (500 MHz, CDCl3 + DMSO-d6): 6.64 (dd, J ) 6.0 and
0.9 Hz, 1H), 6.44 (s, 1H), 6.07 (s, 1H), 4.40 (ddd, J ) 9.5, 6.2 and 2.2
Hz, 1H), 3.92 (s, 3H), 3.24 (m, 2H), 3.15 (dd, J ) 18.7 and 9.5 Hz,
1H), 3.01 (dd, J ) 18.7 and 2.2 Hz, 1H), 2.61 (m, 2H).
A solution of acid 46 (23 mg, 0.066 mmol), scandium trifluoro-
methanesulfonate (33 mg, 0.061 mmol) and lithium perchlorate (70
mg, 0.066 mmol) in dry nitromethane (0.7 mL) was heated at 60 °C
for 4 h. The resulting brown solution was concentrated and chromato-
graphed eluting with 1-2.5% methanol: methylene chloride to afford
47 (7 mg, 32%) as a white solid, mp > 350 °C.
IR (film): 3185, 1732, 1697, 1583, 1541, 1448, 1341, 1189, 1120,
1
833, 804 cm-1. H NMR (500 MHz, CDCl3 + DMSO-d6): 10.20 (br
[R]D) -511° (c ) 0.6, 10:1 CHCl3: methanol), lit.25 [R]D) -544°
(c ) 0.0145, 10:1 CHCl3:methanol). IR (film): 2922, 2850, 1757, 1686,
1628, 1601, 1556, 1483, 1442, 1361, 1138, 1061, 1035 cm-1. 1H NMR
(500 MHz, CDCl3 + DMSO-d6): 6.60 (d, J ) 6.2 Hz, 1H), 6.40 (s,
1H), 4.31 (ddd, J ) 9.3, 6.2. and 2.2 Hz, 1H), 3.88 (s, 3H), 3.34 (m,
2H), 3.06 (dd, J ) 18.7 and 9.3 Hz, 1H), 2.85 (dd, J ) 18.7 and 2.2
Hz, 1H), 2.55 (m, 2H). HRMS Calcd for C17H12O7: 328.0583. Found
328.0582.
Aflatoxin B2a 48. To solution of lactone 47 (7 mg, 0.021 mmol) in
dry methylene chloride (0.5 mL), at -78 °C, was added 1.0M di-iso-
butylaluminum hydride (50 mL, 0.05 mmol). After 1h, at -78 °C, the
solution was treated sequentially with ethyl acetate (2 mL) and 2M
Rochelle’s salt (2 mL). After warming to room temperature the layers
were separated, and the aqueous layer washed with ethyl acetate (3 ×
5 mL), dried (MgSO4) and concentrated in vacuo. Falsh chromatography
eluting with 5% methanol: methylene chloride afforded 48 (4 mg, 57%)
as a white solid, mp 198-201 °C, lit.29 mp 217 °C.
s, 1H), 6.47 (s, 1H), 5.89 (s, 1H), 4.09 (q, J ) 7.1 Hz, 2H), 3.80 (s,
3H), 3.14 (t, J ) 7.6 Hz, 2H), 2.52 (t, J ) 7.6 Hz, 2H), 1.20 (t, J )
7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3 + DMSO-d6): 172.1, 160.6,
160.1, 158.5, 155.7, 155.5, 110.6, 103.3, 95.0, 93.5, 60.4, 55.6, 33.7,
31.4, 14.0. HRMS Calcd for C15H15IO6: 417.9913. Found: 417.417.9918.
4-3-Carboethoxyethyl-8-iodo-5-methoxy-7-(5-oxo-2,5-dihydro-
furan-2-yloxy)coumarin 42. A round-bottom flask containing coumarin
40 (200 mg, 0.431 mmol), 3 (103 mg, 0.517 mmol), Pd2dba3‚CHCl3
(11 mg, 0.011 mmol), ligand (R,R)-6 (22 mg, 0.032 mmol) and
tetrabutylammonium chloride (50 mg, 0.129 mmol) was subjected to
three cycles of evacuation followed by filling with argon. To the purged
flask was added freshly distilled methylene chloride (4 mL) and the
resulting purple solution, which slowly becomes orange/brown in color,
was stirred at room temperature. After 12 h, the resulting brown reaction
mixture was concentrated in vacuo and chromatographed eluting with
diethyl ether to afford aryl ether 42 (212 mg, 89%) as a slightly yellow
solid. Recrystallization from chloroform: petroleum ether afforded 42
as a white solid, mp 198-199 °C.
[R]D) +71.9° (c ) 0.77, CH2Cl2). IR (film): 3107, 2981, 1795,
1729, 1587, 1462, 1339, 1213, 1160, 1117, 1040, 1006, 881 cm-1. 1H
NMR (500 MHz, CDCl3): 7.59 (dd, J ) 5.7 and 1.5 Hz, 1H), 6.84 (s,
1H), 6.45 (d, J ) 5.7 Hz, 1H), 6.44 (d, J ) 1.5 Hz, 1H), 6.15 (s, 1H),
4.20 (q, J ) 7.1 Hz, 2H), 4.00 (s, 3H), 3.29 (t, J ) 7.6 Hz, 2H), 2.63
(t, J ) 7.6 Hz, 2H), 1.30 (t, J ) 7.1 Hz, 3H). 13C NMR (125 MHz,
CDCl3): 172.1, 169.2, 159.4, 159.0, 158.7, 155.4, 155.1, 149.3, 125.7,
113.6, 107.1, 101.1, 97.0, 68.9, 60.8, 56.4, 33.7, 31.5, 14.2. Anal. Calcd
for C19H17IO8: C, 45.62; H, 3.43. Found: C, 45.47; H, 3.68.
Characterized as a 2:1 mixture of â:R anomers. [R]D ) -428° (c )
0.4, 10:1 CHCl3: methanol). IR (film): 3407. 2921, 2850, 1759, 1614,
1591, 1554, 1439, 1380, 1210, 1139, 1056, 828 cm-1
.
â anomer: 1H NMR (500 MHz, CDCl3 + DMSO-d6): 6.38 (d, J )
6.2 Hz, 1H), 6.19 (s, 1H), 5.60 (d, J ) 5.0 Hz, 1H), 3.98 (dd, J ) 8.2
and 6.2 Hz, 1H), 3.79 (s, 3H), 3.27 (t, J ) 5.5 Hz, 2H), 2.47 (t, J )
5.5 Hz, 2H), 2.24 (d, J ) 13.4 Hz, 1H), 2.18 (ddd, J ) 13.4, 8.2 and
5.0 Hz, 1H).
R anomer: 1H NMR (500 MHz, CDCl3 + DMSO-d6): 6.35 (d, J )
6.0 Hz, 1H), 6.21 (s, 1H), 5.34 (dd, J ) 7.0 and Hz, 1H), 4.03 (ddd,
J ) 8.8, 6.0 and 2.0 Hz, 1H), 3.81 (s, 3H), 3.24 (t, J ) 5.0 Hz, 2H),
2.48 (t, J ) 5.0 Hz, 2H), 2.35 (ddd, J ) 13.1, 4.4 and 2.0 Hz, 1H),
2.06 (ddd, J ) 13.1, 8.8 and 7.0 Hz, 1H).
2,3,3a,8a-Tetrahydro-2-oxo-4-hydroxy-6-methoxy-â-(2′-carbo-
ethoxyethyl)-5-furo[2,3-b]benzofuranacrylic acid δ-lactone 43. To
an orange suspension of aryl iodide 42 (100 mg, 0.20 mmol) and bis-
(acetonitrile)palladium(II) chloride (5 mg, 0.019 mmol) in DMF (2 mL)
under argon, was added triethylamine (24 µL, 18.3 mmol) and the dark
orange solution placed in a 60 °C oil bath. To the reaction mixture
was added a DMF (1 mL) solution of triethylamine (53 µL, 40.8 mmol)
and formic acid (15 µL, 18.4 mmol), and the resulting orange solution,
which slowly became yellow, was heated for 1 h. The reaction mixture
was taken into diethyl ether (50 mL) extracted with 1N hydrochloric
acid (25 mL), 10% sodium bicarbonate (25 mL), brine (25 mL), dried
(MgSO4) and filtered. Slow addition of petroleum ether resulted in the
crystallization of 43 (70 mg, 93%) as a white solid, mp 191-192 °C.
[R]D) -433.1° (c ) 0.41, CHCl3). IR (film): 2950, 1798, 1729,
Aflatoxin B1 49. A solution of aflatoxin B2a (48) (4 mg, 0.012 mmol)
in acetic acid (0.5 mL) was treated with acetic anhydride (0.1 mL) and
the resulting clear solution was stirred at room temperature for 20 h.
The solvents were removed in vacuo and the resulting pink solid
dissolved in toluene (0.1 mL). The solution was heated at 240 °C in a
small sealed tube for 15 min. The resulting brown solution was applied
to a preparative TLC plate which was eluted with 5% methanol:
methylene chloride to afford aflatoxin B1 (49) (0.9 mg, 24%) as a white
solid, mp 255-8 °C, lit.25 mp 268-9 °C.
[R]D ) -549° (c ) 0.09, CHCl3), lit.25 [R]D ) -562° (c ) 0.115,
CHCl3). IR (film): 2948, 1758, 1688, 1630, 1595, 1555, 1484, 1441,
1
1629, 1608, 1486, 1436, 1372, 1200, 1156, 1112, 986, 957 cm-1. H
NMR (500 MHz, CDCl3): 6.65 (d, J ) 6.2 Hz, 1H), 6.46 (s, 1H), 6.06
(29) Dutton, M. F.; Heathcote, J. G. Chem. Ind. 1968, 418.
9
J. AM. CHEM. SOC. VOL. 125, NO. 10, 2003 3099