Furan-Terminated N-Acyliminium-Initiated Cyclizations
J . Org. Chem., Vol. 63, No. 20, 1998 6927
cyclohexane (12 mL) was stirred vigorously at 25 °C for 3 min
to yield 0.294 g of a colorless oil. The crude mixture was
purified by chromatography on a column of silica gel (230-
400 mesh, 20 g, 10 mm o.d., ethyl acetate-hexanes 30:70, 10
mL fractions) using the flash technique. Fractions 20-43
provided 0.070 g, 28%, of furanoid compound 74 as a yellow
semisolid. 1H NMR (300 MHz, C6D6): δ ) 7.70 (d, J ) 8.1
Hz, 2), 7.27 (m, 2), 7.12 (m, 1), 6.16 (s, 3), 4.47 (m, 1), 4.00 (m,
1), 2.62-2.40 (2), 2.19 (m, 3), 1.80 (m, 1), 1.31 (m, 1). IR
(neat): 1734, 1687, 1603, 1553, and 762 cm-1. MS (FAB): m/z
(rel intensity) 255 (18), 254 (M+ + 1, base), 253 (M+, 55), 252
(30). HRMS (EI): calcd for C16H15NO2 253.1103, found
253.1092.
Fractions 50-78 provided 0.139 g, 51%, of dicarbonyl
compound 75 as a white solid, mp ) 107-109 °C. 1H NMR
(300 MHz, C6D6): δ ) 7.96 (m, 2), 7.22-7.13 (3), 4.29 (m, 1),
3.30 (dd, J ) 17.6, 7.4 Hz, 1), 2.86-2.75 (2), 2.48 (m, 1), 2.26
(dd, J ) 17.6, 3.3 Hz, 1), 2.20-1.95 (4), 1.41 (m, 1), 1.07 (m,
1). IR (mull): 1698, 1684, 1597, and 1439 cm-1. MS (FAB):
m/z (rel intensity) 273 (19), 272 (M+, base), 270 (12), 186 (54).
HRMS (FAB): calcd for C16H17NO3 + H1 272.1286, found
272.1294. Anal. Calcd for C16H17NO3: C, 70.83; H, 6.32; N,
5.16. Found: C, 70.67; H, 6.36; N, 4.98.
(2). IR (neat): 1716, 1692, 1645, 1468, 1444, 1412, 1325, 1259,
1241, 1197, 1167, 1128, 1111, 1067, and 1001 cm-1. MS (EI):
m/z (rel intensity) 354 (M+ + 1, 46), 180 (28), 173 (20), 166
(base), 165 (35). Anal. Calcd for C18H18F3NO3: C, 61.19; H,
5.13; N, 3.96. Found: C, 61.52; H, 5.04; N, 3.69.
1-Aza -4,5-(2,3b -(5-[p h en yl]fu r yl))b icyclo[4.4.0]d eca n -
10-on e 80 a n d 1-Aza -5-(2-oxo-2-[p h en yl]eth yl)bicyclo-
[4.4.0]d eca n e-4,10-d ion e 81. According to the general pro-
cedure for the cyclization of carbinolamides, a two-phase
mixture of HCO2H (2.5 mL), carbinolamide 70 (244 mg, 0.856
mmol), and cyclohexane (11 mL) was stirred vigorously at 25
°C for 3 min to yield 0.206 g of a viscous, colorless oil. The
crude mixture was purified by chromatography on a column
of silica gel (230-400 mesh, 20 g, 10 mm o.d., ethyl acetate-
hexanes 30:70, 10 mL fractions) using the flash technique.
Fractions 14-30 provided 0.022 g, 10%, of furanoid compound
80 as a viscous, colorless oil. 1H NMR (300 MHz, C6D6): δ )
7.72 (brd, J ) 7.2 Hz, 2), 7.27 (m, 2), 7.13 (t, J ) 7.3 Hz, 1),
6.22 (s, 1), 5.26 (dd, J ) 12.7, 5.5 Hz, 1), 3.89 (m, 1), 2.71 (m,
1), 2.50-2.10 (4), 1.72 (m, 1), 1.40-1.10 (3). IR (neat): 2933,
1639, 1466, and 762 cm-1. MS (FAB): m/z (rel intensity) 268
(M+ + 1, base), 267 (M+, 53), 266 (27). HRMS (EI): calcd for
C
17H17NO2 267.1259, found 267.1266.
1-Aza-4,5-(2,3b-(5-[4-m eth oxyph en yl]fu r yl))bicyclo[4.3.0]-
n on a n -9-on e 76 a n d 1-Aza -5-(2-oxo-2-[4-m eth oxyp h en yl]-
eth yl)bicyclo[4.3.0]n on a n e-4,9-d ion e 77. According to the
general procedure for the cyclization of carbinolamides, a two-
phase mixture of HCO2H (2 mL), carbinolamide 68 (0.201 g,
0.667 mmol), and cyclohexane (8 mL) was stirred vigorously
at 25 °C for 3 min to yield 207 mg of a colorless oil. The crude
product was purified by chromatography on a column of silica
gel (230-400 mesh, 20 g, 10 mm o.d., ethyl acetate-hexanes
1:5, 10 mL fractions) using the flash technique. Fractions 15-
26 yielded 0.038 g, 20%, of furanoid compound 76 as a pale,
yellow solid, mp ) 141-143 °C. 1H NMR (300 MHz, C6D6): δ
) 7.67 (d, J ) 8.8 Hz, 2), 6.90 (d, J ) 8.8 Hz, 2), 6.10 (s, 1),
4.51 (m, 1), 4.04 (t, J ) 7.8 Hz, 1), 3.37 (s, 3), 2.54 (m, 2), 2.20
(m, 3), 1.83 (m, 1), 1.37 (m, 1). IR (mull): 1698, 1684, 1673,
1500, 1444, and 838 cm-1. MS (EI): m/z (rel intensity) 284
Fractions 50-80 provided 0.125 g, 51%, of dicarbonyl
compound 81 as a pale yellow solid, mp ) 128-129 °C. 1H
NMR (300 MHz, C6D6): δ ) 7.95 (d, J ) 6.9 Hz, 2), 7.24-7.14
(3), 5.00 (m, 1), 3.30 (dd, J ) 17.9, 5.6 Hz, 1), 3.06 (m, 1), 2.76
(m, 1), 2.58 (m, 2), 2.22 (m, 4), 1.35 (m, 2), 1.04 (m, 2). IR
(mull): 1714, 1687, 1650, 1596, and 1440 cm-1
. MS (FAB):
m/z (rel intensity) 287 (M+ + 1, 20), 286 (M+, base). Anal.
Calcd for C17H19NO3: C, 71.56; H, 6.71; N, 4.91. Found: C,
71.47; H, 6.68; N, 4.76.
1-Aza-4,5-(2,3b-(5-[4-m eth oxyph en yl]fu r yl))bicyclo[4.4.0]-
d eca n -10-on e 82 a n d 1-Aza -5-(2-oxo-2-[4-m eth oxyp h en yl]-
eth yl)bicyclo[4.4.0]d eca n e-4,10-d ion e 83. According to the
general procedure for the cyclization of carbinolamides, a two-
phase mixture of HCO2H (2 mL), carbinolamide 71 (0.213 g,
0.677 mmol), and cyclohexane (9 mL) was stirred vigorously
at 25 °C for 3 min to yield 0.224 g of a viscous, colorless oil.
The crude mixture was purified by chromatography on a
column of silica gel (230-400 mesh, 20 g, 10 mm o.d., ethyl
acetate-hexanes 30:70, 10 mL fractions) using the flash
technique. Fractions 12-20 provided 0.0085 g, 4%, of furanoid
compound 82 as a viscous, colorless oil. 1H NMR (300 MHz,
C6D6): δ ) 7.68 (d, J ) 8.7 Hz, 2), 6.90 (d, J ) 8.7 Hz, 2), 6.16
(s, 1), 5.29 (m, 1), 3.95 (brs, 1), 3.66 (m, 1), 3.39 (s, 3), 2.74 (m,
1), 2.50-2.15 (3), 1.70-1.20 (4). IR (neat): 2932, 1640, 1613,
1500, 1463, and 834 cm-1. MS (FAB): m/z (rel intensity) 299
(M+ + 1, 20), 298 (M+, base), 297 (85), 296 (24). HRMS (EI):
calcd for C18H19NO3 297.1365, found 297.1370.
(M+ + 1, 20), 283 (M+, base), 282 (26). Anal. Calcd for C17H17
-
NO3: C, 72.07; H, 6.05; N, 4.94. Found: C, 71.75; H, 6.17; N,
4.73.
Fractions 38-50 yielded 0.124 g, 62%, of dicarbonyl com-
pound 77 as a yellow solid, mp ) 135-137 °C. 1H NMR (300
MHz, C6D6): δ ) 8.00 (d, J ) 8.9 Hz, 2), 6.75 (d, J ) 8.9 Hz,
2), 4.29 (m, 1), 3.36 (dd, J ) 17.4, 7.0 Hz, 1), 3.28 (s, 3), 2.84
(m, 2), 2.49 (m, 1), 2.30 (dd, J ) 17.4, 3.5 Hz, 1), 2.22-1.90
(4), 1.43 (m, 1), 1.14 (m, 1). IR (mull): 1711, 1702, 1676, 1605,
1578, and 1440 cm-1. MS (FAB): m/z (rel intensity) 303 (M+
+ 1, 20), 302 (M+, base). HRMS (FAB): calcd for C17H19NO4
+ H1 302.1392, found 302.1399. Anal. Calcd for C17H19NO4:
C, 67.76; H, 6.35; N, 4.65. Found: C, 67.58; H, 6.34; N, 4.63.
1-Aza -4,5-(2,3b -(5-[4-t r iflu or om e t h ylp h e n yl]fu r yl))-
bicyclo[4.4.0]d eca n -10-on e 78 a n d 1-Aza -5-(2-oxo-2-[4-
tr iflu or om eth ylp h en yl]eth yl)bicyclo[4.4.0]d eca n e-4,10-
dion e 79. According to the general procedure for the cyclization
of carbinolamides, a two-phase mixture of HCO2H (5.0 mL),
carbinolamide 69 (504 mg, 1.43 mmol), and cyclohexane (20
mL) was stirred vigorously at 25 °C for 3 min to yield 0.523 g
of a yellow oil. The crude mixture was purified by chroma-
tography on a column of silica gel (230-400 mesh, 20 g, 10
mm o.d., ethyl acetate-hexanes 15:85, 10 mL fractions) using
the flash technique. Fractions 20-38 provided 0.110 g, 23%,
of furanoid compound 78 as a pale, yellow semisolid. 1H NMR
(300 MHz, C6D6): δ ) 7.48-7.08 (5), 6.15 (s, 1), 5.24 (dd, J )
12.8, 5.8 Hz, 1), 3.97 (m, 1), 2.65-2.10 (6), 1.40-1.05 (2). IR
(neat): 1718, 1683, 1639, 1617, 1447, and 846 cm-1. MS (EI):
m/z (rel intensity) 336 (M+ + 1, 22), 335 (M+, 99), 334 (25),
Fractions 32-42 yielded 0.1088 g, 51%, of dicarbonyl
compound 83 as a yellow solid. 1H NMR (300 MHz, C6D6): δ
) 7.99 (d, J ) 8.9 Hz, 2), 6.75 (d, J ) 8.9 Hz, 2), 5.00 (m, 1),
3.33 (dd, J ) 17.5, 5.0 Hz, 1), 3.29 (s, 3), 3.10 (m, 1), 2.79 (m,
1), 2.68-2.54 (3), 2.25 (m, 3), 1.36 (m, 2), 1.06 (m, 2). IR
(neat): 1715, 1675, 1642, 1601, 1576, and 1172 cm-1
. MS
(EI): m/z (rel intensity) 315 (M+, 1), 200 (11), 167 (10), 166
(base). Anal. Calcd for C18H21NO4: C, 68.55; H, 6.71; N, 4.44.
Found: C, 68.36; H, 6.43; N, 4.19.
P r ep a r a tion of Mon ok eta l 85. To a solution of 45 (188.8
mg, 0.84 mmol) in CH2CI2 (3 mL) cooled to -24 °C in a dry
ice-CCl4 bath was added TMSOCH2CH2OTMS (174.4 mg,
0.845 mmol) followed by TMSOTf (31 drops). The cooling bath
was maintained at -24 °C for 3 h; then stirring was continued
overnight while allowing the yellowish solution to warm to
room temperature. Pyridine (15 drops) was added, the solution
was cast into saturated aqueous NaHCO3 (5 mL) and the
aqueous layer was extracted with CH2CI2 (4 × 5 mL). The
combined organic layers were washed with 1 N aqueous HCl
(10 mL), saturated aqueous NaHCO3 (10 mL), and brine (10
mL), dried (Na2SO4), and concentrated in vacuo to provide 85.3
mg of a yellow oil. The crude product was purified on a column
of silica (230-400 mesh, 20 g, 20 mm o.d., ethyl acetate-
methylene chloride-methanol, 8:1:1, 4.5 mL fractions) using
the flash technique. Fractions 13-23 provided 210.8 mg, 93%,
265 (28), 264 (26). HRMS (EI): calcd for
335.1133, found 335.1136.
C18H16F3NO2
Fractions 55-90 provided 0.2522 g, 50%, of diketone 79 as
a viscous, pale yellow oil. 1H NMR (300 MHz, C6D6): δ ) 7.76
(d, J ) 8.1 Hz, 2), 7.40 (d, J ) 8.1 Hz, 2), 5.02 (m, 1), 3.10 (dd,
J ) 17.9, 6.3 Hz, 1), 3.05 (m, 1), 2.77 (m, 1), 2.52 (m, 1), 2.42
(dd, J ) 17.9, 4.1 Hz, 1), 2.23 (m, 4), 1.38 (m, 2), 1.17-0.96